2 Flashcards
Lines of the brain
1- frontal, processing info, relaying sensory info
2 Temporal
3- parietal
4- occipital
Prefrontal cortex- frontal lobe anterior to motor cortex- universally decided have subregions-dorsolateral pfc, ventrolateral pfc, ventromedial pfc, dorsomedial pfc
Makes up a lot of the brain- linked to executive functions- process that function on short sided behaviour to acheieve a goal- self control, goal monitoring, problem solving- probably many areas of brain as it is very complex- distributed networks
When PFC damaged- executive function impaired- cannot assign specific roles to pfc subregions- probably due to interaction of these regions and the communication via the rest of the body
It’s receives the sensory info and sends it to the areas of brain to carry out a function- moving,
Cortical areas named by parts of skull
Cortical areas named by parts of skull
Organization of brain- linked to function based on the lobes of the brain
Lobes- assigned before anyone knew the brain- relied on parts of skull as landmarks
Main bones= match up to the lobes
Areas of the brain
Areas of brain named based on the bone plates that lie around it- arbitrary way of divided complicated organ into manageable lobes- much more complex than one function
Central sulcus and Sylvia’s fissure- gyri- grooves in brain- seperated brain
Cerrebelum- thinner, has thinner gyri
Lobe that has singular function- occipital- vision- relay on it to make sense of surroundings- big part of our brain functioning= needs large area- not only area= sends it to other areas to make sense of what we are seeing- object identity, recognizing faces, making sense of shapes
Temporal- processes hearing, dedicated to language, has memory storage, many functions, hippocampus located here
Parietal- interpret touch and somatic sensory info, touch sensations create movement and identify movement
Frontal- posterior- has production of movement, plans movement, brocade area- controls speech, has executive functioning area
Frontal- important for behaviour functioning
Functional division of the cortex
Executive
Action
Sensory Functionally distinguish it
Executive- most associated with abnormal psych- linked to many disorders- addiction, depression, schizophrenia- linked to frontal cortex functioning
Phineas gage
Wilder Penfield reported the “silent cortex” - areas of frontal cortex appeared to have no function.
Ex. Phineas Gage’s personality changed so radically that he was “no longer Gage.”
.what are executive functions- what traits- planning, self control, causing movement= *GUESS
Many people don’t know the meaning- took science years to find out what rental cortex does and how it regulates the rest of the body
Penfield- probed brain with electromagnetic for epilepsy- done during consciousness- want to make sure you don’t damage important areas- some regions when stimulated- led to vivid scenes, emotions, smells- burnt toast
Even though he did this couldn’t figure out functions for prefrontal cortex- called t silent cortex
Caused them to look at other cases- Gage- iron rod blew through skull- he survived another 12 years- left side of PFC was destroyed- he had changes in personality and mood- no longer himself- was balanced, smart after was reactive, aggressive couldn’t hold a job- everyone noticed
Frontal lobe- regulating the balance between animal and human behaviour
From Silent Lobes to CEOs
Does the prefrontal cortex separate human from animal?
Brodmann (1912)
The relative size of prefrontal cortex is nearly twice as large as any other animal.
Gage- brought attention to brain what seperated human brain from other animals
Brodmann- used cellular markers for animal brains- compared size of human and animals frontal lobe- we have a much greater portion of frontal lobe- occupies 30% in humans, 4%- in cats, 17% in monkeys
The prefrontal cortex is twice as large than predicted based on evolution- frontal lobe has evolved to be bigger
size of human frontal lobes
The absolute size of human frontal lobes is 3x larger than great apes. If size matters what about the absolute size o the brain. The absolute size of human frontal lobes is 3x larger than great apes.- humans have a bigger frontal lobe- relativ sense- twice as big
Parietal cortex size
Other intelligent animals have bigger brains than humans, but the parietal cortex is proportionately larger.
What about in intelligent animas- they have a larger parietal not a frontal cortex
Parietal- sensation, sense of enviroment, knowing where you are
Deficits Following Frontal Lobe Damage
Case study:
3 patients with prefrontal lobe damage.
personality changes.
Normal movement and perception.
No impairment of intelligence.
Case study evidence supports that PFC is important in behaviour and personality
3 patients had damage to prefrontal lobe- had change in behaviour or personality- and normal movement, defects in behaviour
Multiple Errands Task
How are those with frontal lobe damage impacted in real life- asked to go to market- given to do list- have to visit multiple places seek out info without aids
Frontal lobe damage- struggled- strayed from where they wanted to go, less organized- brain may be disorganized
Deficits in Strategy Application Following Frontal Lobe Damage
Patients made more errors vs controls
Executive Functions
Flexible, goal-directed behaviour in response to internal and external cues.
Executive function- broad term-focused on goal directed behaviour
Higher level cognitive processes- people better than animals
Action selection VLPFC
Self regulation DLPFC
Weighing alternatives OFC
Goal setting PFC
Plannng DLPFC
Structures and functions of the cortex
Lobes not limited to a single function.
General organization of sensory (posterior) and motor/action behaviours (anterior).
Executive behaviour localized to prefrontal cortex.
Executive functions focus on controlling goal-directed behaviours.
Executive functioning not limited to PFC
Executive behaviour- only in PFC- if damages not good at it
Linking behaviour to function of prefrontal cortex
Major Subdivisions of the Prefrontal Cortex (PFC)
Dorsolateral (DLPFC)
Ventral (VPFC)
Orbital (OFC)
PFC- frontal lobe
Takes sensory info and relies it to other areas of brain
PFC- most of frontal lobe- except for motor cortex
DL-PFC and working memory
DLPFC- towards the top and to the side- most recently evolved, goes under long period of maturation
PFC last to develop- still not fully mature
Time management, working memory, cognitive flexibility-change actions, planning, holding info in mind- problem solving, directing and maintaining attention
Connecting to hippocampus, emotions important here
If have PTSD- have deficits in DLPFC- cognitive and memory problems, can cause lack of emotion, attention deficit problems
Some say sig difference in hemispheres- left side- approach behaviour nd happy emotions left= avoidant
DLPFC interacts with others area of brain- parietal lobe
DLPPFC- linked to object permanence- subject has to find object after certain delay- able to do this with more developed DLPFC- 2 years old
DLPFC defects- have deficits In working memory- less activation there when have no object permanence- when develop it have more activity in DLPFC
Role of DL-PFC in
Cognitive Flexibility
Lots of evidence links executive function to PFc
Cognitive flexibility- think of multiple things at once, strop task- hard for most people
Cog flexibility- crucial aspect of frontal lobe processing those with frontal lobe damage- mentally rigid
Wisconsin task- solution is constantly changing- have to not stick to what you think is role- have to be able to change thinking
Those with frontal lobe injury- cant change mental state or approach to problem
Associated to DLPFC
Ventrolateral prefrontal Cortex (VL-PFC)
Motor Inhibition
Updating Action Plans-Right posterior
Decision uncertainty-Right middle
Control attention-Left
Well connected
Functionally different from DLPFC
Hemispheres have different functions
Right- motor inhibition, updating actions, control attention
No go task
Measure reaction time to stimulus- add decision- inhibit behaviour- only click when no patter
Increased VL-PFC Activity During No-Go.
Shows ‘contrast’ of activity between Go and No-Go tasks. More activity on ‘No-Go’ will appear as brighter red.
Inc of activity in the no go- have to inhibit behaviour
Compare left and right hemisphere activity.
The Cognitive Reflection Test
(updating action plans / override response)
Right VLPFC- updates actions plans, controls attention
Left VLPFC- more important for attentional control, resisting temptations
Makes decisions based on connections from other areas, amygdala, hippocampus, temporal lobe, thalamus
VLPFC- connected to rest of brain
VMPFC- helps VLPFC in social decisions, social nctioningm suppressing negative emotions
CRT- measure tendenc to override problem solving processes that are incorrect- predicts how they can overcome cog biases
Increased VL-PFC Activity while adjusting decisions
On the fly activity adjustment induced greater activity in right ventrolateral prefrontal cortex
CRT- measure ability to reflect on question and inhibit first response that comes To mind- inc activity in right side
Ventromedial prefrontal Cortex (vm-PFC)
Connected with amygdala,hypothalamus, PAG
Emotional regulation
Orbitofrontal (Orbital-Frontal) Cortex
(OFC)
signalling rewards/punishments
decision making
L vs R
Regulating decisions in socia situations
Introspective decision making
Learn from mistakes
Value-based decision-making
(OFC)
Monkeys choose between two types of juice (A and B; where A is preferred) offered in different amounts. Behaviourally, there is a trade-off between juice type and juice quantity.
In experiments- monkeys have preferred juice- monkeys choose juice a when juice b is offered- if you offer 4 times more of b- will pick b
They are swayed by quantity of juice and flavour
the cell’s activity varies with the offer ‘type’.
When the choice (above) is roughly equal (no difference in value), OFC neurons respond the least.
Only when there is a value preference do we see elevated activity.
OFC- plays a role in this- when its equal- doesn’t respond
Value difference= activity difference- causes them to weigh options
Linking experience to reward
A(fMRI) study using show that the more we like what we eat, the more active our OFC.
FMRI during these task- show selective activation on anterior parts- link to pleasantness rating
Pleasant- higher- more activity in OFC
Executive functioning= very vast term- depends on the area but is goal directed behaviour- higher level cog processes
Cells of the Nervous System
Embryonic stem cells that form the nervous system become two primary cell types:
Neurons
Glial cells
We start at stem cells in specialized Neurons transmit information in the form of electrical signaling.
Sensory, motor, interneurons
Glial cells provide metabolic support, protection, and insulation for neurons.
Filial- support- insulate neurons, part of blood brain barrier
Features of neurons
Common features of neurons:
Cell body
Dendrites
Axon
Cell body • Cell body; contains nucleus and other organelles.
Ex. Mitochondria for ATP
Dendrites - branches upon which incoming fibers make connections (at synapses) with other neurons
receiving stations for excitation or inhibition
Dendrites- receiving area- information transfer happens between neurons at the synapses
Branches of dendrites lined with receptors- get excited or inhabited
Axon- releases the signal out to the synapses
Many receptors throughout the brain
Axon- conducts electrical signals away from cell body to synapses
Principal parts of neuron
Transmission occurs from the presynaptic cell to the postsynaptic cell
Flow of information:
Synapse dendrite soma axon synapse
Transmission between neurons- happens at axon- axon makes neurons different- transmit info in form of AP
Happens from the presynaptic cell synapsing with the dendrites of another cell AP- generated at axon hillock
Neurons that need the info to transfer fast- myelin sheaths made by glial cells
Terminal buttons- neurotransmitter release
receptor at synapse to the dendrites info goes to cell body, AP is generated at axon hillock travels to terminal button and synapse wth another dendrite
Dendritic spine
Dendrites are covered with short dendritic spines
Dendrites and their spines are constantly modified and canchange rapidly in response to changes in synaptictransmission: #, size, shape, etc.
Dendritic spine- inc surface area, constantly modified- change rapidly based on info in brain and neurotransmitters, the dendrites themselves change in #- inc or Dec, Chang in size and shape
Disorders- have different amount of dendritic spines
Drugs of abuse- change dendritic spines- may be key to drug addicted state
Components of axons
Axons transmit electrical signals from the axon hillock (at the soma) to the terminals.
A neuron usually has one axon, but it may branch to form axon collaterals.
Terminal buttons have synaptic vesicles containing neurotransmitter chemicals.
Axon hillock- goes down to terminals- usually have one axon- can form collaterals the terminal buttons release- dopamine, gaba
Rrelease from synaptic vesicles
Most axons are wrapped with myelin sheath, a fatty insulating coating created by layers of glial cells:
Schwann cells
Oligodendroglia
Fatty insulated cells made by Schwann cells in the periphery,
Oliginderia- myelinated nerves in the spinal cords and brain
Both are glial cells- protect neurons
Multiple sclerosis caused by determined myelin sheaths= less communication
Myelin sheath
Node of Ranvier = break in myelin sheath increases speed of
AP conduction Breaks in the sheath= nodes of fancier- AP jump along= spreads up
Myelin breaks down- nerotransmission doesn’t happen as well
Schwann cells: form myelin sheaths in peripheral nervous system (PNS); wrap only one axon; release growth factors and promote regeneration of damaged axons
Oligodendroglia: form myelin sheaths in central nervous system (CNS); wrap many axons
Astrotes: provide structural support for neurons and help maintain ionic balance in the extracellular environment; take up excess NTs- maintain homeostasis- take up excess transmitters
Microglia: remove dying cells by phagocytosis at sites of nerve damage; responsible for immune response- waste removal, immune response
All glial cells important
May contribute to disorders
Transcription of genes
Soma (cell body) performs most metabolic functions.
The nucleus contains pairs of chromosomes.
Chromosomes = strands of DNA; gene = section of chromosome coding specific proteinComplementary RNA made by transcription factors: nuclear proteins that bind to DNA, transcribing it to make RNA-Experiences can affect gene transcription
Protein translation in cytoplasmic ribosomes.
More interested in neurons but glial do cause abnormalities
Cell body- metabolic functions, energy production
Nucleus- has chromosomes- genes- read by mRNA to make proteins0 very important
Transcription can be modified- dna doesn change much- expression of genes changes- transcription factors- gets read by enzymes after mRNA to make proteins- experiences and stressors- effect gene transcription= epigenetics
Epigenetics
Epigenetics: control of gene expression by chromosome modifications that do not affect the DNA code.
Ex. DNA Methylation: attachment of methyl groups to a gene reduces its expression (blocks translation).
Epigenetics- change gene expression not gene itself
DNA methylation- methyl attached to gain= blocks transcription- doesn’t turn into protein
Acetylation of chromatin(dna wrapped around his tones)- can be changed when added acetylate - makes it unwind DNA= more likely to be transcribed
Chang expression of dna
Trauma, drug use, causes acetylation- changing expression of genes
When chromatin tails acetylated, charges open up chromatin (part B) allows transcription factors to bind increases transcription
Methylation of histone tails (part C) pulls chromatin tighter prevents transcription factor binding reduces transcription
Opens chromatin- allows transcription to bing
Methylation- maes it harder to read
May explain the differences not caused ny genes- differences in twin- how experiences change behaviour
Axoplasmic transport
Axoplasmic transportUses cytoskeleton: network of microtubules and neurofilaments that provide shape and structure to the cell. Microtubules form a track that proteins travel along by the action of motor proteins. Proteins that are made in the soma neeed to be transported
Uses or cytoskeleton
Help form a path for proteins- Alzheimer’s- microtubules get tangled causing tangled neurons
Proteins in the Cell Membrane
Proteins in the Cell Membrane
Receptors: cell membrane proteins -initial sites of action of neurotransmitters (NTs), hormones, and drugs.
Enzymes: catalyze biochemical reactions
Transporters: for charged molecules (Ex. amino acids, glucose, metabolic products)
Many proteins - many are receptors= where chemicals bind to
Enzyme- help w biochemical reaction
Transporters- help them get across cell membrane
Resting membrane potential (RMP)
more negative ions (and amino acids) inside the cell, and more positive ions outside.
Distribution f ions in neuron when at rest
Difference in charged ions and proteins= more negative inside then outside
Neurons can get only so positive before reach AP(0-50)
Voltage-Clamp Technique
Allowed H & H to set the membrane potential (clamp it) at any level, and simultaneously measure underlying permeability changes (current flowing across membrane) Used voltage lamp on squid’s
Set membrane potential to level amd stimulate axon and observe ion channel
Electrostatic pressure and concentration gradient
Most ion channels are gated, but some K+ channels are not (=leaky); K+ moves freely
K+ moves into the cell because it is attracted to the negatively charged particles (electrostatic pressure)
K+ moves back out of cell when its concentrationrises (down its concentration gradient)
In open channel- potassium called it of neuron- slowly
Equilibrium potential for potassium (
Equilibrium potential for potassium (EK): when the two forces are balanced. The membrane potential is still more negative inside (~-58 mV).
When two forces are balanced- potassium wont move(-58)- these. Forces generate action potential
Equilibrium reached when ions are balanced
Interior- high concentration of negative charge
Ions cant diffuse across membrane except for with channels
Neuron at rest- most are closed
But potassium can be open- they d not allow other ions- only few are open- the intercellular concentration is higher then outside- potassium is moving in and out of the cell- diffusion and electrical forces- when come in balance= potassium equilibrium= no movement
Maintain resting potential and returning it- because of sodium potassium pump takes 3 Na out for every k moved in- ions pumped against their concentration gradients – r=needs energy
All cell membranes are polarized
Action potential (AP): a rapid change in membrane potential that is propagated down the length of the axon
Threshold potential for AP firing = ~-50 mV -Voltage-gated Na+ channels open, Na+ flows in; generates rapid change in membrane potential to more +ve = depolarization
Polarized- more negative inside
AP- happen at myelin sheath- every once and a whole
Rest, receptors bound, channels open- change into positive= AP
Voltage gated channel is open- when cell gets more pos- sodium rushes in causing It to become pos- potasssium- leaves
How are AP caused
Various stimuli can cause an AP and open ion channels:
electrical change
chemical (taste, drugs, smell, neurotransmitters)
mechanical (touch, pressure, sound)
light (vision, photodetection)
temperature (hot and cold receptors)
Small amounts of ion channels opening causes small, local changes in ion distribution and potential differences called local potentials-Depolarizations and hyperpolarizations
Many stimuli can cause AP
Small changes in the ions- graded potential-
If Na+ channels open, Na+ enters cell and causes local depolarization excitatory post-synaptic potential (EPSP)
If Cl– channels are stimulated to open, Cl– enters cell and results in hyperpolarization, which is inhibitory. inhibitory post-synaptic potential (IPSP)
If gated K+ channels open, K+ leaves the cell which also results in hyperpolarization.
Depolorazied- sodium channel open sodium flows in- EPSP- ion come in make it more pos
CL- channels open- make it more negative- harder to generate AP-
Local potentials and action potentials
Graded: larger stimulus greater magnitude of hyperpolarization or depolarization
Summation: several small depolarizations big changes
Bigger stimuli- lead to bigger responses= leads to AP
Summation- adding the stimulations t reach potential
Action potentials- only depolarize
If summation of local potentials reaches the threshold, large numbers of Na+ channels open and Na+ rushes into the cell very quickly.
-Causes rapid change in membrane potential from –50 mV to +40 mV = rising phase of AP
Getting stimulation and inhibiting- reach temporal summation- fire an AP
Stages of the action potential
Resting potentials
Threshold
Happening very quick
430 km/hr
Have thought- say it= instant
Different channels going on all the time
Potassium= leaky channel- always open
AP Refractory Periods
Absolute refractory period - the time following an AP where a stimulus can’t elicit a second AP due to closure of Na+ channels
Relative refractory period - the time following an absolute refractory period when the threshold for initiation of a second action potential is increased: Na+ channels recover from inactivation and K+ channels close
absolute- sodium channel closed- can relate to disorderds- constantly firing
nodes of Ranvier
In myelinated axons, regeneration of the action potential occurs only at nodes of Ranvier
The conduction seems to jump along the axon = saltatory conduction.
Less energy is needed because Na+-K+ pumps are only at the nodes. - AP moves along axon because Na+ ions spread passively to nearby regions, which changes the membrane potential to threshold, which opens more Na+ channels.
AP- only generated at nodes of fancier- sodium ions spread across the myelin
tetrodotoxin (TTX)
Some drugs alter AP conduction by blocking the voltage-gated Na+ channels (e.g., Novocaine): These drugs are used for local anesthesia.
Bacteria within the pufferfish generate a toxin called tetrodotoxin (TTX) TTX blocks Na+ channels, paralyzing its victim
Cocaine- block sodium channel- touch info doesn get to brain
TTX- block sodium channel get paralyzed but conciuos- sodium cant get I n
2 major classes: Local graded potentials & Action potentials
Graded- differ in size- more stimuli bigger response= signal lessens as it goes o rest of body
AP- happens or doesn’t, not graded, same intensity through out spatially- how many across pace, temporal- time
AP fires based on how many AP you see
Development of the brain
Brain development depends upon:
Maturation
Learning
We can refine this understanding by learning how:
Neurons develop
Their axons connect
Experience modifies development (Plasticity!)
Neural development- depends on maturation and learning-brain changes from learning
Is it due to brain just maturing- growing in size- no learning plays a part- new synaptic connections
Brain development needs both learning and maturation
Start in fertilization- sperm fertilizes egg- cell division starts
Day 15- considerend embryo
At day 20- neural plate starts to form- a couple weeks after conception- brain starts to form- neural plate is first neural tissue- becomes a groove- forms a neural tube
The neural tube closes
Maturation of the embryo Brain
Human CNS begins to form when embryo is ~3 weeks old:
Dorsal surface thickens, forming neural tube surrounding fluid filled cavity
Anterior end enlarges, sinks under skin surface
Hindbrain, midbrain, forebrain, spinal cord
Our CNS- brain and spinal score form at 3 weeks- neural tube forms- completed at 4 weeks
Cerebral hemispheres- side of brain formed
Brain gets bigger and grows- gets bumps that become parts of brain
Forebrain- covers midbrain and hindbrain- rest is spinal cord in CNS
Fluid (CSF)-filled cavity becomes central canal & 4 ventricles (walls = neuron production)
The rest of the neural tube becomes the spinal cord
Has cerebral spinal fluid- neural cavity filled with CSF- becomes spinal cord and ventricles in brain(fluid filled space) where neurons are produced
During brain development- the neurons start in walls of ventricle
Neural tube folds on to itself
Forebrain- gets bumpy- form gyro- covers midbrain and Hindbrain
Changes happen during development- brain gets bigger but looks the sa,e
Brain weight
At birth, brain weighs ~350 g
By the first year, brain weighs ~1000 g
By 18 years old, (adult) brain weighs ~1400 g
18 years is adult- no finished (especially prefrontal cortex) until 30 brain develops front to back
Brain develops in proportion with body- but connections change brain through life
The Development of Neurons
The development of neurons in the brain involves the following processes:
Neurogenesis
Migration
Differentiation
Maturation
Synaptogenesis
Pruning & Cell Death
Myelination
Neurogenesis happens first- around 2 months- rest is out of order – once neurons formed- migrate
Later processes- continue after birth
Littleneurogenesis occurs through life
Neurogenesis
The production of new cells/neurons in the brain
Early in devt, cells lining the ventricles (in the subventricular zone) divide
Stem cells continue to divide
Neurons (E42) or glia migrate to other locations
>250,000/min!
Almost all form within ~28 weeks of gestation
Proliferation of new neurons
Primarily in early life- but some areas do form neurons
Cell lining ventricles(subventricular zone) dividing a lot and specializing- continue to divide and form cells- some become neurons or glial cells(migrate)
Cell division at this time produces one stem cell and one neuron- have stem cell and neuron each division of ste, cell
Sem cell stays there neuron leave and
migrate Around 100 billion neurons
Developing of neurons is happening very fast- if anything happens during this development that causes abnormal development
Born before 28 weeks- brain not fully developed- more vulnerable to abnormalities
Environment changes and neuron production is inhibited
Stem cells in pancreas, hippocampus, can develop new stem cells- turn into neurons
Nerve cells in hippocampus in adult brain- need these them cells of new neurons to learn new info
In general new neurons do not form in other areas
Migration
The movement of the newly formed primitive neurons and glia to their eventual locations
Some don’t reach their destinations until adulthood
Occurs in a variety of directions throughout the brain
Chemicals known as immunoglobulins and chemokines guide neuron migration
After become neuron or glial cell- migrate to new location
Some don’t reach destination to adulthood
Damage to brain- can damage migration
Moves in different directions- some slide along glial cells(help neuron migrate)- radial glia
Tips of migrating neurons form growth cone- has feelerssensing environment- guiding neuron
Chemicals- help neuron find way- act as guide-
Migration requires precise chemical environment
Differentiation
Local environmental signals (ie. chemicals produced by other cells) influence the way cells develop & form layers in the cortex
Intercellular signals progressively restrict the choice of traits a cell can express
G X E
Local environmental signals(neuron reached destination) has signals and chemicals that influence development of cell and layers it forms in cortex
Differentiation forms these layers
Cells release different neurotransmitters,otters- because of neuron itself- restricts development of certain genes
All have same gene- environment activates certain genes
Maturation
Formation of axon & dendrites
The axon grows first: either during migration or once it has reached its target-followed by the development of the dendrites
Maturation and ifferation go hand in hand
Forms axon and dendrites- give neuron shape
As neuron mature- form structures- axon grows first
After migrating- dendrites start to form- happens before birth continues forever- as experiencing- dendrites change
Axon grow 1000 time faster
Newborn- broccas area- don’t have many dendritic formation
Have same cell body across time- by 2 years old have many more dendrites- as forms synaptic connections
Dendritic branches & spines
In lab animals- the formation of dendritic spine and branches- influenced by environment and environment simulation (friends vs no friends)
Autisms- partly due to abnormal neural maturation- have different dendrites
Have less dendritic spines,, size is different
Environment- chemical and social- lead to growth and maturation o neuron
Pathfinding by Axons
Axons must travel great distances,form correct connections
Sperry’s (1954) research on newts shows axons follow a chemical trail to reach appropriate targets
Growing tips of axons also respond to cues from:
Cell adhesion molecules (CAMs)
Tropic molecules
Netrins
Axon and dendrites need to find way- what to synapse with
Axon travels great distanced to connect
Not easy for axons to find way
In 1920- graphed extra leg on salamander axons grew into it causing them to move together
1954- cut the optic neurve and rotated it- found the axons grew back to original target- had to travel different difference but went to were they should \
The chemical environment is important to signal correct axonal growt
CAMS- growth cone and growing axon, stick to it or repealed high causes guidance and tropic molecules- attracts or repels neurons
Netrins
EMX2 PAX6
Protein got rid of certain axon
Emx2- in normal- more posterior- causes normal development
Mutate emx2- pax6 tries to shift it- causing change in development
Mutaepax6- causes change in development
Proteins and correct level- important for normal development
Axon guidance
A growing axon follows a oath of molecules attracted by chemicals and repelled by others. Eventually axons sort themselves over the surface of their target by following this molecular trail
Axon follow molecular trail- certain proteins guiding axon along causing proper development
Synaptogenesis
Formation of synapses
Begins before birth, occurs throughout life: neurons are constantly forming new connections (& discarding old ones!)
Slows significantly later in life
Each neuron may synapse with >1000 others adult brain estimated to have > a quadrillionsynapses!
Formation of synapse- connect neurons
Synapses change all the time- slows down in later life
Synapses dependent on genetic info and experiences
- Pruning & Cell Death
When axons initially reach their targets, they form synapses with several cells (in approximately the correct location).
Postsynaptic cells strengthen connection with the most appropriate cells and eliminate connections with others.
Elimination = synaptic pruning -depends on the pattern of input from incoming axons
Chemical gradient is not perfect don’t use it you lose it
Cells may die as we;;- depends on environment and input from axon- selection process- neural darwinism- only most stimulated survive
Huge synaptic pruning in puberty bug decrease in amount of synapses
As solidifying personality- selective pruning
Influenced by a lot of factors
The Life Span of Neurons
Different cells have different life spans:
-Skin cells are the newest; most under a year old
-Heart cells tend to be as old as the person
Mammalian cerebral cortices form few new neurons after birth
Some cells survive longer than other- neurons not often replaced
Determinants of Neuronal Survival
Neuronal targets determine who survives
Nerve growth factor (NGF): protein released by neuronal targets, promotes survival & axonal growth
The brain’s system of overproducing neurons, then applying apoptosis (cell death) if they don’t get NGF, enables the exact matching of the number of incoming axons to the number of receiving cells
Sympathetic ganglian- muscles that synapse with axon that come from ganglia- ganglia- don’t determine how many neurons- target of the synapse- decides what synapse stays
Muscles creates NGF- any neurons without enough ngf- experience apoptosis
Brain is overproducing neurons- expecting some to die
Only neurons that make sig connections survive
U to 50% of neurons produced may die off
Neurotrophins
Chemicals that promote the survival and activity of neurons (i.e., NGF, brain-derived neurotrophic factor (BDNF))
Increase dendritic branching & axonal growth
Neurons that are not exposed to NGF after making connections undergo apoptosis
NGF- neurotrophin
NGF- during development
BDNF takes over in adult hood- important for learning- need it for synaptic remodeling
After maturation don’t need ngf
Healthy adult system- has not neurons that failed to make connections
Don’t have enough- cortical shrininking
Pruning and cell death
The massive elimination of nerve cells is part of normal development and maturation
Depends on appropriate environmental stimulation
Ex. The visual cortex is actually thicker in blind people due to a lack of visual stimuli
It cannot prune out ineffective neurons
Happens to about 50%
Big elimination- depends on environment stimulation- need appropriate enviroment y
Don’t have visual stimuli- brain doesn’t now which neurons to prune- within appropriate simulation- don’t prune synapses that should
Myelination
Glia (oligodendrocytes)
Speeds up transmission of neural impulses in many vertebrate axons
First occurs in spinal cord and then in the hindbrain, midbrain and forebrain
Occurs gradually for decades
Slower stage
Happening across time
Myelin sheath gets put over axons-c overs most neurons
Astrostyces and oligodendrocytes( produce myelin in CNS) after
Happens after neurogeneiss
Happens in spinal cord first
Schwann cells- create myelin in PNS
Myeliation- tends to occur with developemental milestones- more neurons myelinated- able to learn more words
Some et ions myelanted earlier
Myelination vulnerable to environement
The Vulnerable Developing Brain
Early stages of brain development are critical for normal development later in life & are remarkably similar across species.
Ex. FASD
The dendrites of FASD children are short with few branches
Decreased Glu andincreased GABA
Lower neurotrophins
Toxic chemicals, infections, malnutrition- doesn’t hae same impact in adulthood as it does n development
FASD- repeated exposure to alchol- suppresses glutumate(excitatory transmitter) and releases GABA- causes too much inhibition - causing shorter dendrites with fewer branches, lower exposure to neurotrophins- not as much growth factor, causes neronal death
Not just alchol- pesticide, led
FASD- affects child different based on time and quantity of alchol
Many have behavioural problems
Hard to diagnose- assess exposure during pregnancy, neurodevelopmental impaired ent, physical features typical of FASD- many don’t have this
Neurobehavioural features
Of FASD
Hard and soft neurologic signs (including sensory-motor signs).
Brain structure (occipitofrontal circumference- indirect measure of brain size, magnetic resonance imaging, etc.).
Cognition (IQ).
Communication: receptive and expressive.- receive instructions, communicate with others
Academic achievement.
Memory-
Executive functioning and abstract reasoning. Switch tasks, inhibit functions
Attention deficit/hyperactivity.
Adaptive behaviour, social skills, social communication.
Degree of severity for FASD
Considered impaired – if on a measure- 2 std below average
More than 2 std away- outside of nom
Have a mean- see the scores for Ind and compare to average
Hard signs- impaired in basic motor and sensory skills- reflexes
Soft signs- Any neurological abnormality- not defined by any specific abnormality- cant pinpoint what the issue is
All these can be affected
Look at to find severity of FASD
Postnatal Brain Development
Newborn brain is fully functional, but lacking.
Dramatic growth of synapse.
Greatest growth in cortex
Brain looks like adult brain
After birth- growth of synapse
By 3 years old number of synapse- has increased drastically- Lots of development
Neuronal development activity- peak at age 3, forming social connections, cognitive skills
Pet scans show activity
Most active areas emit radioactive activity
PET scans give a fuzzy idea of the tremendous amount of development taking place in a brain.
Refinement
Maturation does not always reflect growth; but rather, refinement!
Maturation is also refinemen- not growing in size but synapses get refined
Brain becomes more detailed- develops stringer connection
Pruning is refining synapses
Neural-Darwinism
By the end of the 1st year, there are ~100 billion neurons, but even more connections
50-80% overgrowth of connections.
Only the best and most efficient will survive (Edelman, 1987)
Brain overproduces synapses- doesn’t have lots of functionality- needs to be reduced bases on experience- lots of competition between synapse- most efficient synapses survive- establish themselves in neural circuitry
Imaging Studies of Brain Development
Progressive Changes in Cortical Thickness
Trajectory of cortical gray-matter density in children scanned longitudinally every 2 years for 8 years. The reduction in gray- matter density begins in primary areas and spreads to secondary and teritiary regions.
Looked at gray matter density and matter loss and reduction
Scanning child every 2 years- reduction in grey matter reduction of synapses and dendritic- starts in primary regions- where Brain first matures- control basic functions
Other areas- mature later- not needed to survive projectors of maturation- keeps going to age 30 or beyond
Linking Cortical Thickness to Behaviour
Cortical regions where change in cortical thickness was associated with change in IQ.
B. Scatter plot for the relation between IQ changes and CTh changes at the peak vertex inferior pre-central gyrus;
C. Changes in cortical thickness at the same peak vertex represented in panel B.
Loose synapses- inc white matter- these changes coincide with behavioural changes
Relationship between iq and cortical thickness- iq seems to stay constant
In some people- inc or Dec in iq- when look at change in cortical thickness- thickness is bigger, iq is higher
Individual differences in rate of change in cortical thickness, related to changes in iq
Grow bigger brain, increase in iq score
Mechanisms of plasticity
If there is more activity in one eye, the connections from the deprived eye to visual cortex shrink , while the connections from the good eye expand.
Neural plasticity- brains ability to change
Developing neural connections from eyes- compete for space
Suture cat eye closed- deprive eye of stimulation- connections fail to develop, not stimulation visual cortex
Shows there is a mechanism of neuron that allows it to detect aqvtivity, most activated- form strongest connections, least likely to die off
Branching Patterns of Geniculocortical axons
This change due to simulation
After closure, deprived eye has no dendritic spines- no activity- leads to skinny neuron
The effect of enriched experience
Rats were trained to reach into a tube to retrieve a food reward with their preferred paw (rats, like humans, are right- or left-handed). The rats were then trained to use their non-preferred paw to grasp the food.
After training to use the non-preferred paw, examined changes in branches from pyramidal neurons.
Providing more stimulating environment
Putting toys in rats environment, giving them friends
Rats right or left handed- in this, give rat extra practice, does it change brain activity- rat has to use non dominate paw
The peramital neurons in the cortex- had difference in neuronal structure, difference in dendritic brans
Dendritic morphology of pyramidal neurons in layer III of the somatosensory cortex in a rat housed in standard (left) and enriched (right) environments, as viewed in confocal imaging
B – the trained neurons, inc branching- assume inc in synapse
Rats were trained to reach into a tube to retrieve a food reward with their preferred paw (rats, like humans, are right- or left-handed). The rats were then trained to use their nonpreferred paw to grasp the food.
After training to use the nonpreferred paw, examined changes in branches from pyramidal neurons.
The number o branches- not a big difference
But it is significant
Effects of enriched experience on rats
Rats raised in an enriched environment develop a thicker cortex and increased dendritic branching.
Measurable expansion of neurons has also been shown in humans as a function of physical activity.
Research looking at fish- raised in isolation- have neurons with fewer branches
With friends- have more branches
In humans- physical activity- adding physical stimulation= more dendrites and dendritic spine
An enriched environment is ‘enriched’ in relation to standard laboratory housing conditions.
A combination of complex inanimate and social stimulation
Effects of elements of enrichment, such as learning and exercise, on cell proliferation (one day post BrdU exposure) and neurogenesis (four weeks post BrdU exposure) in the dentate gyrus.
Enrichment is leading to new neurons being formed and new dendrites
BRDU- incorporated into newly synthesized dna
Put brdu on environment- gets substited for another molecule, use it as marker for neurogensis
Control- no enrichment, have new neurons but not a lot
In any of enrichment- more neurogenesis happening in hippocampus
Detect small changes, can do this with developed organisms
Any enrichment can lead to neurogenesis
Extensive practice of a skill changes the brain in a way that improves the ability for that skill.
Areas marked in red showed thicker grey matter among professional keyboard players
Practicing a skill- enriched their environment, brain has changed, inc grey matter(synapses) in certain areas
Enriching own life= can lead to brain changes
ADHD Prevalence
Prevalence: 3-5% of school-age children
5-10% of the entire population
3x to 6x more prevalent in males than females
Typical changes as children mature
If synaptic development impacts behaviour- disorder can occur from abnormal synapse development \
ADHD core symptom- not able to inhibit behaviour- executive functioning
Most prevealent developmental disorder
Many factors influence onset of adhd- hormones, enviroment
Core symptoms change with age
Development disorder-changes as mature
Attention deficit/hyperactivity disorder (ADHD)
= the best studied, and one of the most common, of the childhood disorders
In DSM-5, ADHD is listed as a neurodevelopmental disorder: Viewed as brain-based.
Children with ADHD are motorically and often verbally hyperactive; have problems maintaining focus; show impulsive or erratic behaviours.
Often create problems in schools and families
1/3 retain diagnosis
A third of those diagnosed in childhood have it in adult hood
Symptoms of adhd
Inattention
Does not pay attention, loses things frequently, is easily distracted, is forgetful, has problems with organization, does not seem to listen or to follow instructions.
Hyperactivity
Fidgets with hands or feet and squirms in seat, leaves seat when inappropriate, runs around or climbs excessively, often talks excessively to self and others, has difficulty engaging in quiet activities, frequently gets in trouble.
Impulsivity
Blurts out responses while others are talking, has difficulty waiting his or her turn, often interrupts or intrudes on others.
Inattention- linked to academic problems
Functional impairment – causing issues
Symptoms must be present during childhood
Symptoms present before age 7
Clinically significant impairment in social or academic/occupational functioning
Some symptoms that cause impairment are present in 2 or more settings (e.g., school/work, home, recreational settings)
Not due to another disorder (e.g., Autism, Mood Disorder, Anxiety Disorder)
Adhd subtypes
2 Subtypes: hyperactivity/impulsivity, and inattention the primary symptoms of ADHD.
Main type of symptom the child presents with will determine the specifier:
inattentive type adhd i- more common in girls(may be ignored)
hyperactive/impulsive type- adhd h
hyperactive-inattentive or combined type adhd hi
Adhd
Comorbidity: 50%
Prevalence: ~2% in preschool-aged children, 6% among children and adolescents, 4% among adults.
Developmental Trajectory. Most require chronic approach to management through adolescence and adulthood. -most important long-term issue is increased risk for developing another psychiatric disorder.
Nearly half of adults with ADHD also have a mood or anxiety disorder. 50% have another disorder- most common is conduct or oppositional defiant, anxiety isorders
In later years- ma experiences depression or substance use
Most diagnosed need long term approach
Adhd etiology
Exact cause is unknown -biological cause expected: multiple risk factors interact
Generally reduced brain size- reduction in gray matter, abnormalities in the metabolism of DA & NE- noradrenaline
MRI studies linked ADHD with brain abnormalities:-prefrontal cortex, associated with executive functioning-basal ganglia, associated with higher motor control, learning, memory, and emotion regulation
Abnormalities in pfc, basal ganglia
Recent studies have found delay in reaching thickness of cerebellum- slower developed- symptoms in child but not adult
Adhd and the brain
No obvious brain differences
The amount of energy the brain is using is less
Less activity in PFC
Overacticity in basal ganglia
Delayed Frontal lobe development and ADHD
Delayed frontal lobe development
At age 6- less developed than normal
Normal pattern of development is delayed by 3 years
Most difference in pfc
Leads to smaller Brain size
Differences in brain maturation, structure, and function:
Frontostriatal circuitry
Prefrontal cortex
Basal ganglia
Major implications for attention and response inhibition
Fronstostrial region and its connections- most important in the dysfunction f those with adhd
Less activity
Cant hold memory, cant pay attention, cant inhibit behaviour
Anatomical pathway
Prefrontal cortex- connected with other areas
These areas connected through neurostransmiter pathways
If one part not functioning- mess up loop
Parkinson’s- damage substantia nigra
Under activity in PFC- in adhd
How can an area so low in metabolic activity cause behavioural hyperactivity
Reduced fronto-straital activation
Neurotransmitter differences, particularly in levels of
Dopamine
Norepinepherine
Serotonin
Things in frontal cortex- not enough dopamine, dopamine system not working
Reduced striata
Different pathways involved in adhd
Dopamine transporter-
Dopamine created- gets packed in vesicles- goes to receptor, dopamine transporter recycles dopamine- may be abnormality in transported= dopamine dysfunction
Adhd brain abnormalities
Fronto-striatal circuitry is disrupted, both functionally- connection with other areas and structurally- look different.
frontal cortex is responsible for inhibition of attention and behavioural responses to salient but off task events
basal ganglia is responsible for the motor response to these interfering events.
Disruption of dopamine regulation in fronto-striatal circuit leads to decreased dopamine release & blunted response of receptors, resulting in behavioral presentation seen in ADHD
Less dopamine released, receptor not being stimulated properly= behavioural presentation in adhd
Adhd heritability
Heritability may be 77%
No gene linked directly
Gestational factors: -pregnancy and delivery complications-prenatal toxin exposure: poor diet, antidepressant use, exposure to mercury, lead, alcohol, caffeine, cigarettes, illicit drug use, etc.
Psychosocial factors: low socio-economic status, large family size, paternal criminality, poor maternal mental health, child maltreatment, foster care placement, family dysfunction
Very genetic- genetic component
Genes involving dopamine- have no found adhd gene
Hard to find one link of adhd- often occur together
Gene environment interaction
Gene-environment interactions (G X E)
-ADHD results from an interaction between genes and the environment
-similar to diathesis-stress perspective
Ex. ADHD & ODD more common when children with certain type of dopamine receptor gene also had inconsistent parenting.
Ex. ADHD symptoms present in children with a certain dopamine transporter gene only when mother smoked during pregnancy.
G X E- any phenotypic event that resulted from both gene and environment
Have genetic vulnerability- experience adverse event- causes activation of gene
Gene and environment interact to make disorder more likely to present
Adhd treatment
Pharmacotherapy: stimulant medications -Ritalin (methylphenidate), Dexedrine (D-amphetamine). Increase DA & NE release, and block reuptake
Most likely symptoms to respond to medication are hyperactive, restless, impulsive, disruptive, aggressive, and socially inappropriate behaviours.
Academic, social, and emotional difficulties generally do not improve
Side effects commonly observed.- headaches, cant fall asleep, inc BP
Usually pharmacotherapy
Inc dopamine and norepinephrine and block transported that reuptake
Hyperactive presentation- drugs work best for it
ADHD: Non-Drug Treatment
Psychoeducational interventions
Parent training helps parents develop skills to manage their child’s behaviour: Contingency management- rewarding certain behavior most effective.
Family therapy, CBT, individual psychotherapy, social skills training seem to be less effective.
Teach parent and teacher techniques
Does development end at 25?
Grey matter continues to decline up to 60 years of age.
White matter peaks ~50 years of age
Total Brain matter levels-
Grey matter- declines up to 60, slow decline then levels off, may dip again at death
White matter- peaks at 50 then decreases
Grey matter- associate w inc in white matter(myelination of axon)
CSF- inc across life- more space in Brain
Development progressing- still can Learn
Alzheimer’s Disease
Associated with a gradually progressive loss of memory, mostly occurring in old age
Affects 50% of people over 85, and 5% of people between 65-74 years old.
Early onset seems to be influenced by genes
99% of cases late onset
No drug treatment is currently (very) effective
End of life
Brain atrophy in Alzheimer’s
Big spaces were ventricles were, neuronal loss
AD and proteins
Alzheimer’s disease is associated with abnormal genes that lead to an accumulation and clumping of the following brain proteins:
Amyloid beta protein
Abnormal form of the tau protein clumps, producing tangles
Amyloid beta deposit in brain cause neuronal degeneration
Tau protein- cause take tangles- clumps of degenerated neurons
Breaks down an neurons degenerate
Cerebral Cortex of an Alzheimer’s Patient
Cell in prefrontal cortex, neuronal deteration
Plaque- all old stuuf and tangle has formed- cells alll tangled
Forming amyloid plaques
As it is being made, amyloid precursor protein (APP) sticks through the neuronal membrane
Enzymes cleave beta-amyloid protein, releasing it into the space outside the neuron
Clumps of beta-amyloid collect and begin to form a plaque
Betamyloid get formed form app
Small piece is logged in neuron rest is outside, enzymes clip off the beta amyloid- in normal it gets turned off and flushed with outer membrane
In alzeiimer- get snipped at wrong place- each beta- amyloid causing plaque and neuronal death
AD biological changes
Profusion of neurofibrillary tangles (Tau protein)
Caspase theory: Beta-amyloid stimulates caspase formation apoptosis
Both plaques & NFTs occur early in AD
Hippocampus & entorhinal cortex
Memory and retention of learned information Tau protein maintains stability of microtubule
In Alzheimer’s tau changes- cant support microtubules- get wound around each other, cause tangles, nerve cant communicate- die
Happens ealr in the process- progress substantially before see issue- progressing for years
Ad and the blood brain barrier
http://www.iflscience.com/health-and-medicine/slowdown-brain-s-waste-removal-system-could-drive-alzheimer-s/
BBB tight in young, healthy ppl
Gatekeeper, but also waste removal
β-amyloid movement slower in older people, builds up damages brain and BBB more β-amyloid. Also other toxins enter!
BBB ‘leakier’ in older people with MCI vs cognitively normal old people
Could be issue with blood brain barrier- keeps stuff out of brain and takes bad stuff out of brain beta amyloid- movement slower n older people- bbb should get it out, if damages bbb, cause it to be leaky, toxins get into brain
Memory problems- have leaky bbb
AD & ACh
Number of ACh cells declines with age
The final step in ACh synthesis catalyzed by the enzyme choline acetyltransferase (ChAT)
In AD, ChAT is less active
= The cholinergic hypothesis of AD Anti-AD medications: Preserve ACh by inhibiting acetylcholinesterase (AChE) less enzymatic degradation Nuclei in areas are main source of ach- get loss in alzeiherms \ In presynaptic area- Chat- regulation ach, in Alzheimer’s- chat is less active= less ach= less activity in brain Begins as deficiency in ach
Synapses
Synapse: describes the specialized gap that exists between neurons
Neurotransmitter binds to receptor- causes change- open channel, lead to secondary effects
When a drug binds to receptor may activate or inhibit it- have different effects n receptors
Some will bind to them but not activate
Bind to receptor= ligand(no matter what)
Natural ligand- neurotransmitter
Not alll act the same- don’t lead to same behaviour
Can you control Brain functioning
Neurons communicate via neurotransmitter transmission at the synapse(tiny gap)
Synapse exist between neurons(not touching) and neurons are interacting at synapse- have neurotransmitter release and receptor
Anxiety
Over active amygdala- causes specific reactions such as freezing
Control amygdala- control anxiety
In anxiety- overactive amygdala and underactive GABA- over activating some areas under activating other areas- case symptoms o anxiety
Anti anxiety- hack stress cycle- inhibit amygdala
Gaba agonist- increases gaba activity- inc gaba function, inc inhibition- decrease activity in other area
Rats with more musicinol gaba- did not learn fear response
2nsides of the synapse
Presynaptic neuron: neuron that delivers the synaptic transmission
Postsynaptic neuron: neuron that receives the message- has receptors
The Discovery of Chemical Transmission at Synapses
German physiologist Otto Loewi
The first to convincingly demonstrate that communication across the synapse occurs via chemical means
The great majority of synapses rely on chemical processes
Led to the development of psychiatric drugs
.nerves- axons stimulate muscles by releasing neurotransmitter(chemical)
Synaptic transmission can be both- most is chemical
Revoloutionized drug research- can give chemicals to alter brain functioning
Nerves Send Messages by Releasing Chemicals
1 vagus nerve of frog heart stimulates
2 fluid transferred to second container
3 both frogs heart rates decrease after stimulation Stimulated vagus nerve of heart- decrease in heart beat
Transferred fluid of heart to another frog- observed decrease in heartbeat (has to be chemical
Chemical Events at the Synapse
Otto Loewi’s (next) findings:
Stimulating the vagus nerve released something that inhibited HR; stimulating a different (accelerator) nerve released something that increased HR
Realized that he was collecting and transferring chemicals, not loose electricity
Neurotransmitters (NTs): chemicals that travel across the synapse and allow communication between neurons
Stimulate different nerve- accelerate heart- inc heart rate
Inhibition and excitation happening
Has to be chemical
Identify NT
Transmitter must be synthesized or present in neuron.
2 When released, transmitter must produce a response in target cell
Transmitter’
3 Same receptor action must be obtained when
4 There must be a
transmitter is experimentally mechanism for removal after placed on the receptor.
the transmitter’s work is done. To be neurotransmitter- made in neuron
Removed- diffuse, reuptake, diolved
Storage of NT
Vesicles: tiny spherical packets located in the presynaptic terminal where typical NTs are held for release
Exocytosis: bursts of release of NT from the presynaptic terminal into the synaptic cleft
Triggered by an AP
Most synthesize in presynaptic terminal- packed in vesicles- stay there until AP-
Vesicles- release neurotransmitter upon AP
AP reaches terminal- neurotransmitter releases
Chemical synapse
Transmission across the synaptic cleft by a NT takes fewer than 0.01 microseconds
Transmission floats across synaptic cleft
Attach to receptor most common synapse- at theaxon to dendrite
Importance of calcium
Step 2: The Importance of Calcium
1 When an action potential reaches the voltage-sensitive terminal, it opens calcium channels.
2 Incoming calcium ions bind to proteins, forming a complex.
3 This complex binds to vesicles, releasing some from filaments and inducing others to bind to the presynaptic membrane and to empty their contents by exocytosis. AP Combes- voltage activated channel open- forms complex with binding proteins of neurons lead to vesicle release
Calcium causes complex to form- vesicle release
NT Attaches to receptor and has effect on postsynaptic cell
Can have second messenger affects
Activating Receptors onthe Postsynaptic Cell
The effect of a neurotransmitter depends on its receptor on the postsynaptic cell
Transmitter-gated or ligand-gated channels are controlled by a neurotransmitter: These are ionotropic.
Ionotopic – ligan bind to receptor- ion Chanel open- ions flow through
Ionotropic effects
Occur when a NT attaches to receptors and immediately opens an ion channel to allow ions to move across the membrane
Most effects:
Occur very quickly (sometimes less than a millisecond after attaching) & are very short lasting
Happens immediately within Ms
Happening all the tike
Ion channel open and closes quickly
Metabotropic Effects and SecondMessenger Systems
Occur when NTs attach to a receptor and initiate a sequence of slower & longer-lasting metabolic reactions
Metabotroppic- slower- metabolic reaction
NT initiate sequence of reactions ]
NT binds to receptor, has intraceelur effect- G protein acticated( energy storing molecule)
Opens ion channels but is much slower
Or couples to ion- has many effect and can last longer- destroy dna
When neurotransmitters attach to a metabotropic receptor, it bends the receptor protein that goes through the membrane of the cell
Bending allows a portion of the protein inside the neuron (the G protein) to react with other molecules
NT attach- G protein receptor- bends protein- G protein can detach- go and has effect
G-Proteins
G-protein activation: coupled to guanosine triphosphate (GTP), an energy storing molecule
Increases the concentration of a “second-messenger” = chemical that carries a message to different areas in the cell
The second messenger communicates to areas within the cell
May open or close ion channels, alter production of activating proteins, or activate chromosomes
Proteins coupled to energy storing molecule gtp
Can go and have second messenger effect- activate protein or enzyme
Negative Feedback
Negative feedback in the brain is accomplished in two ways:
Autoreceptors: receptors that detect the amount of transmitter released and inhibit further synthesis and release
Postsynaptic neurons: respond to stimulation by releasing chemicals that travel back to the presynaptic terminal where they inhibit further release-retrograde neurotransmitter One transmission has happened – don’t want it to happen forever- negative feedback- tells it to stop
Autoreceptor- on presynaptic terminal- sense own neurotransmitter
Auto receptor activated- inhibit transmission release
Ppostsynaptic- respond to simulation of self- releases neurotransmitter- travels back to cell and inhibits activity at presynaptic terminal
Can be happening at anytime
Small-Molecule NT Receptors
Many have both ionotropic and metabotropic receptors
Gaba- open sodium- decreases membrane potential of cel
Typical neurotransmitter molecules
Neuropeptides
Metabotropic effects utilize a number of different neurotransmitters
Neuropeptides are often called neuromodulators
Release requires repeated stimulation
Released peptides trigger other neurons to release same neuropeptide
Diffuse widely and affect many neurons via metabotropic receptors
Use metabotropic receptors
Neuron synthesizes these in cell body and dendrites
Transported top other areas of cell
Released at dendrites, cell body, side of axon- anywhere
Modulate activity of nearby cells
Release needs multiple stimulation
Has cascade effect- activates other neurons triggering them to release same neuropeptide
Released- every thing around is effected
Distinctive Features of Neuropeptides
Neuropeptides
Neurotransmitters
Place
Cell body
Presynaptic terminal
synthesized
Place released
Mostly from dendrites,
Axon terminal
also cell body and sides of axon
Released by
Repeated depolarization
Single action potential
Effect on
They release the
No effect on neighbors
neighboring cells neuropeptide too
Spread of effects
Diffuse to wide area
Duration of effects
Many minutes
Effect mostly on receptors of the adjacent postsynaptic cell
Less than a second to a few seconds
Neurotransmitter- contain to synapses
Hormones & the Endocrine System
Chemicals secreted by a gland or other cells that is transported to other organs by the blood where it alters activity
Produced by endocrine glands
Important for triggering long-lasting changes in multiple parts of the body
Hormones are chemicals secreted by glands or neurons
Conveyed in blood stream- released in blood stream and travel throug it, influencing organ behaviour
Hormones convey message to any organ with receptors for it testosterone- in development- causes long term effect
Hypothamalams releases to posterior
Adrenal gland on top of kidney produce cortisol
Proteins and Peptides
Composed of chains of amino acids
Attaches to membrane receptors where they activate second messenger systems
Bind to membrane receptor- causes second messenger responses- metabolic
Stress response
Medical Student in 1925 (17 yrs old)
Noted similarities in symptoms of sick patients.
“Since these were my first patients, I was still capable of looking at them without being biased by current medical thought. Had I known more I would never have asked myself questions, because everything was handled just the way it should be.”
All suffering from different conditions but had similarities
Had sore muscles, increased tonsils
Why would they have similarities
Forward to the 1930’s
-working with ovarian extracts from cows.
Seemed to produce a sickness syndrome (Stress)
Injected rats with ovarian extracts
Made the rats sick
Developed symptoms from injections
Enlarged adrenal gland, loosing hair
More shots= more symptoms
Regardless of what they were injected with, they got sick
Took kidney extract- same thing happened
Sickness syndrome
Not the extract, injecting them repeatedly makes them stressed, causing them to experience sickness- non specific bodily response of stress demands
The General Adaptation Syndrome
Alarm
Body mobilizes to confront the threat
Resistance
Body copes with the threat by fighting or fleeing
Exhaustion
Physiological resources are depleted trying to cope with the threat
Some mechanism in body whos respinse to external stressors- general
Stress response- responds to anything that upsets homeostasis- severe enough= adapt to it
Alarm- body responds to stressor, get stressor
If it doesn’t go away- resistance- adapt to stressor
If it still doesn’t go waway- exhaustion= cant fight threat, no more resources- get sick
He thought only absence of stress- in death- have constant stressors
Body systems responsive to psychosocial variables
The endocrine system
The autonomic nervous system
The immune system
Other body systems respond to stress
All 3 interacting with each other and the brain
initiate stress- feel physical stress
Fight or flight response activated- primitive stress response- fight or run away- biological response to acute stress
Stress initiates a cascade of events
Acute stress response
Sam
Respond quick fight or flight
Chronic stress response
Hpa
Long term
High alert Fight or flight response activated- primitive stress response- fight or run away- biological response to acute stress
Onset of stress- associated with physical responses- fight or flight response
Part of an axis- many systems working together
SAM-
Acute not chronic
Respond quic, readies body fo fight vid flight
HPA-
Complex pathway interacting systems, help respond to constant stressor
Interaction of orans- influence many processes, digestion, immune system,
Mood and emotions affected by it
Energy depletes
2 main stress responses
Autonomic nervous system
Automatic
Amygdala- processes emotional significance of stimulus- mostly eye as negative
Limbic system- adds emotion, feel fear or stress or anxiety
Stress response- involves feeling not just physical
Amygdala sends signals to hypothalamus- control centre between brain and endocrine system- connected to Pituitary gland
Beginning of stress response- starts with perceptual response- what you think is stressful
Amygdala- gives meaning to event
Hypothalamus- has many nuclei and important connections to hormones galnds
Acute stress response
Body threatened by immediate danger
Physical response is immediate- followed by hr increase, sweating- cause by sympathetic nerves-stimulate nerves- release norepinephrine
The adrenal gland relaseing- adrenaline and cortisol
Sympathetic is faster
Hormone release is slower
Nervous system response faster than endocrine response
Happens within seconds
Adrenaline and cortisol- help with fight v flight
Chronic stress response
Stressful events that persist
Perceived by hypothalamus- releases crh acts on pituitary to release acth
Travels to adrenal glands- causes them to release cortisol
Hypothalamus- CRH to pituitary- releases ACTH- goes to adrenal- releases cortisol
Cortisol has negative feedback- continue stress- keep releasing cortisol
Adrenals
Adrenal gland cortex- releases cortisol
Medulla- releases adrenaline or epinephrine
Allostasis
Stress response allows for wide range of adaptive circumstances.
This is ‘allostasis’: achieving stability through change.
It occurs via the ‘stress response’.
Circadian rhythms
HPA activates in morning
Baseline-6
Afte eating goes up
Rises and falls of cortisol
Go back to baseline
Norwegian military during parachute training
How crisis changes during stressor
Studies recruits for military looked at stress response while jumping out of plane
Each days looked at cortisol anterior pituitary releasing hormones, cortisol eleveated before jump
Do more jump- get used to it- reduce cortisol secretion
Less activation of stress
After becoming less stressed to it- have less response
Testosterone and cortisol- antagonistic effect
Everyday stress
Less-dramatic real-life situations also evoke clear endocrine responses
Riding in train
Normal not crowded- a title inc in epinephrine
Crowded= more stressful= greater stress response- longer= more epinephrine
Stress may induce eating
Determine the influence of psychological and physiological variables in determining the eating response to stress
Stress respinse release energy store- chronic level of cortisol- influence eating behaviour
If we depleteenrgy storage in stress- do we tun to higher calories
Stress respinse release energy store- chronic level of cortisol- influence eating behaviour
If we depleteenrgy storage in stress- do we tun to higher calories
During 3 stress session- exposed to cognitive challenges - designed to be stressful- not enough time
Speeches, puzzled, math puzzels
On the stress day- had increased stress activity
Wasn’t instant- lots of cortisol release after test
Mood reactivity- had more negative mood and anxiety
On control day had Dec in negative mood
After stress and on rest day- given basket of snacks- left in room for 30 min- not pressured to eat, invited to
Ate more calories on stress days- relationship between cortisol release and more eating
Total calories consumed on the stress day was significantly related to change in cortisol
Stress response uses energy- need to inc intake
Role of Mother-Infant Interactions
Harry Harlow’s experiments on the effects of extended maternal separation.
Examined maternal separation effect, mother infant reaction is important to developing normal stress response
The ones who did not have access to mother- caged with other animals at time- when got to play with other animals- would not play- would sit together cautiously, seemed stressed
impact of handling
Neonatal handling impacts development.
Environmental manipulation occurring early in life resulted in changes in the adrenocortical axis that persist through the entire life of an animal.
High levels of stress hormones early in life manifest in many ways
Changes in adrenal cortex axis- higher levels of stresss hormones
Stress them by- holding them, seperate mother
If held- still had warmth
Used water maxe to test adults spatial memory- defects emerged as they were older- didn’t have good memory
In handled rats- didn’t show any difference- touch and warmth
In swim maze- hidden platform associate cues- remember where platform is
Differences in cortisol release in response to stress test
Not handled- released more cortisol- effects were delayed
Look at offspring stress hormone receptor
Had more glucocorticoid receptors in hippocampus- more effient negative response- lower levels of cortisol
Affects hippocampus size
Handled rats- don’t loose neurons or cell density
Not handled rats- Dec in hippocampus size- not enough feedback- kills cells in hippocampus
HPA-Axis in parental caring
Parental separation- inc stress response
Depends on the care given
University students described their parents
Those wit could/ unloving parents- more likely to develop illness, higher level of substance abuse and MDD
Experinestress in development has lasting impact on brain developement
Romanian orphanage
Government of Romanian- forced to pay dents of old government- stopped sending money to orphanages
Kids not taken care off- cold, grey dark spaces, many kids in bed
Interacted with kids but not caregivers
Showed us how it impacts the kids
Many of them adopte
Highest cortisol levels- had lowes scores later in motor and cognitive development
Less glucocorticoid receptors- causes changes in kids
Orphaned kids- had decrease rate of glucose metablixation
Had less brain activity overall- less neurons
The timing of deprecation- when it began and how long it lasted- linked to severity of problems
Lived in orphanage for 9 months at least
Compared to Canadian children and early adopted kids from Roman orphanage
In orphanage for long time- more problems
One girl- stayed 8 months then adopted- early child experiences led to abnormal adult behaviour- killed cats, fantasizes abt killing ppl
Diagnosed w conduct disorder then institutionalize
Chronic stress response
Cope with stress
Try to get chronic stress responses balanced- return to baseline- stress doesn’t go away reach exhaustion
Cortisol necessary for normal functioning- immune response, metabolic
Low cortisol can cause fatigue, dehydration
Actuate stress response not stopped- cause chronic stress repsone
Stress can’t be turned of cause secondary symptoms- ulcers, sickness
Antacids- help ulcer pain
Chronic stress- reduces gastric activity- acid secretion unbalanced-damages tissue
Cant turn stress off- not good for body, acute stress is okay- not prolonged
In humans- ruminate
Power of perspective
Researchers looked at stres– lots of stress inc risk of dying by 43%- only if they thought they couldn’t handle stress
Negative view of stress and chronic stress- kills many
Change perspective on stress-
Chronic stress- restrict blood vessels
When told stress is helpful response to threat- had less restricted blood vesssel
Human connection and stress
Stress= pituitary activated- releases oxytocin(social upport and bonding)
Compels you to seek support
Part of stress response- stimulated to bond.
Released into blood stream to act on target- released by hypothalamus activity- axon terminals release oxytocin from anterior pituitary- releases into blood stream
Human connection- mechanism to regulate stress
Oxytocin anti inflammatory- maintains blood cells(help recover from damage)
Stress and SoCal interaction
How much stress- ho much have you helped others in community, friends
Every major stress- inc risk of death but ppl who spent time with helping activities- showed no stress related. Inc In dying- being socially bonded creates resistance ]
harmful effect of stress— can be mediated by oxytocin
Active and stress
Additional support for the notion that more active responding leads to a diminished stress response
Serotonin neurons ost active with repetitive movement
Measured serotonin in cats
No firing when not moving
Walking on treadmill- can it stimulate serotonin release and mimic anti anxiety
Serotonin release reduceing stress respone
Sustained running exercise and HIT
Looked at hippocampus generation
Runners- had more new hippocampus neurons
Different types of exercise- had same effect
Controllability of stress
Stress can be controlled by exercise, connection and perception of stress
F we think we can control and manage it- less stressed
Happy make T cells
Uncontrollable- low T cells
Controllable- if push button may be able to stop shock sometimes- if they believe they had control- inc in T cells
Mindset of controlling stress- changes brain functioning
Belief that you will do things to achieve your goal
Self efficacy
Is thei a relationship between stress and depression- was it managed ny self efficacy
]those with higher self efficacy- believe in themselves- decreased depression.
PFC damaged-
PFC damaged- executive function impaired- cannot assign specific roles to pfc subregions- probably due to interaction of these regions and the communication via the rest of the body
Subdivision of PFC
Prefrontal cortex- frontal lobe anterior to motor cortex- universally decided have subregions-dorsolateral pfc, ventrolateral pfc, ventromedial pfc, dorsomedial pfc
Makes up a lot of the brain- linked to executive functions- process that function on short sided behaviour to acheieve a goal- self control, goal monitoring, problem solving- probably many areas of brain as it is very complex- distributed networks
Temporal
processes hearing, dedicated to language, has memory storage, many functions, hippocampus located here
Parietal
Parietal- interpret touch and somatic sensory info, touch sensations create movement and identify movement
PTSD and DLPFC
If have PTSD- have deficits in DLPFC- cognitive and memory problems, can cause lack of emotion, attention deficit problems
Cognitive flexibility and DLPFC
Lots of evidence links executive function to PFc
Cognitive flexibility- think of multiple things at once, strop task- hard for most people
Cog flexibility- crucial aspect of frontal lobe processing those with frontal lobe damage- mentally rigid
Wisconsin task- solution is constantly changing- have to not stick to what you think is role- have to be able to change thinking
Those with frontal lobe injury- cant change mental state or approach to problem
Associated to DLPFC
Cognitive Reflection Test
Right VLPFC- updates actions plans, controls attention
Left VLPFC- more important for attentional control, resisting temptations
Makes decisions based on connections from other areas, amygdala, hippocampus, temporal lobe, thalamus
VLPFC- connected to rest of brain
VMPFC- helps VLPFC in social decisions, social nctioningm suppressing negative emotions
CRT- measure tendenc to override problem solving processes that are incorrect- predicts how they can overcome cog biases
Schwann cell
Schwann cells: form myelin sheaths in peripheral nervous system (PNS); wrap only one axon; release growth factors and promote regeneration of damaged axons
Oligodendroglia
Oligodendroglia: form myelin sheaths in central nervous system (CNS); wrap many axons
Astrocytes
provide structural support for neurons and help maintain ionic balance in the extracellular environment; take up excess NTs- maintain homeostasis- take up excess transmitters
Microglia
Microglia: remove dying cells by phagocytosis at sites of nerve damage; responsible for immune response- waste removal, immune response
All glial cells important
May contribute to disorders
Cytoskeleton
cytoskeleton: network of microtubules and neurofilaments that provide shape and structure to the cell. Microtubules form a track that proteins travel along by the action of motor proteins.
Electrostatic pressure
Most ion channels are gated, but some K+ channels are not (=leaky); K+ moves freely
K+ moves into the cell because it is attracted to the negatively charged particles (electrostatic pressure)
Concentration gradient
K+ moves back out of cell when its concentrationrises (down its concentration gradient)
