Midterm #1 Flashcards
What is Consciousness
State or quality of awareness – awareness of our thoughts, perceptions, memories, and feelings
What is a Frontal Lobotomy
Outdated surgical approach for treating seizure disorder (epilepsy) that involves cutting the corpus callosum: the bundle of nerve fibers that connect the left and right sides of the cerebral cortex.
Generally effective, but it has unacceptable side effects.
Why can’t we do frontal lobotomy anymore?
Our cerebral hemispheres are critical for our ability to consciously process sensory information (sights, sounds, touch, etc).
What is the left brain responsible for?
The left brain is largely responsible for the right side of the body.
Left brain processes right side of the eyes
Consciousness must be located in the left part of the brain
Language is on the left side as well
What is the Right Brain responsible for?
The right brain is largely responsible for the left side of the body.
Right brain processes left side of the eyes
What is the corpus callosum?
Enables the two hemispheres to share information so that each side knows what the other side is perceiving and doing.
What happens if we cut the corpus callosum?
If it is cut – the hemispheres can’t talk to each other but can talk to the spine
Left hand sometimes seemed to have a mind of its own
What happens if a Slpit brain patient has his eyes closed and touches an object with his LEFT HAND
Cannot identify the object out loud - left hand = right brain
Left brain is responsible for language
What did the sperry lab prove?
When the command ‘laugh’ was directed to the right hemisphere of one patient, he laughed. When asked why he was laughing, he said “you guys come up and test me every month – what a way to make a living!
what is the interpreter theory
Behavior is fully controlled by unconscious processes, and that the function of our left-brain consciousness is create narratives in an attempt to make sense of the world.
What is mind-body dualism
If our intuitions and perceptions are misleading, if the earth is actually spinning and hurtling through space, what can we trust? After doubting everything, even existence itself, Descartes eventually drew a line in the sand and famously stated, “I think, therefore I am.”
What is an ion
If a molecule or single atom has an electric charge, it is called an ion.
Ions form ionic (electric) bonds with each other.
What happens if ionic bonds go in water
Ionic bonds typically break apart (dissolve) in
what is a salt
Molecules held together by ionic bonds
what represents the six most important chemical elements whose covalent combinations make up most biological molecules on Earth.
CHNOPS
carbon, hydrogen, nitrogen, oxygen, phosphorus, sulfur,
what is a ribosome
RIBOSOME – When RNA can catalyze a reaction
Consists of strands of RNA and strands of amino acid (i.e. proteins)
what is an enzyme
When a protein can catalyze a chemical reaction
what is a phospholipid bilayer and what does it do?
Phospholipid are a long strand of fat (lipids) with a phosphate cap
Lipids prefer the company of other lipids – phosphate caps prefer to interact with water
Phospholipids often form bilayer sheets if left undisturbed
When shaken, phospholipids form micelles (soap bubbles)
If your hands are greasy water just bounces off – when you wash your hands…
Prokaryotic cell
Cell membrane filled with cytoplasm
Very long, loose strands of DNA (strings of nucleic acids) and shorter loose strands of RNA
Ribosomes (which are made of strands of RNA and strands of amino acids)
The function of ribosomes is string together the amino acids held by tRNA in the order dictated by the genetic code. Thus, ribosomes make proteins.
Eukaryotic cell (that prokaryotic does not have)
The mitochondria – digest sugar and can grow into ATP molecule
Extract energy from nutrients
Create ATP molecules by digesting sugar molecules
Nucleus
Safely imprisons the cell’s long strands of DNA.
Compacted strands of DNA within a nucleus (Chromosomes)
What is a genome
Provides information necessary to synthesize all cell’s proteins
Sections of the genome that gets transcribed into RNA and translated into proteins
what is a gene
Section of DNA that codes for a specific protein
When a gene is read, that segment of DNA is transcribed into RNA.
After RNA leaves the nucleus; ribosomes translate RNA to create proteins.
What is the basic structure of a neuron
soma/cell body
dendrites
axon
axon terminal
synapse
What is the resting membrane of a neuron
-40mV to -90mV
What are ions and what are they called when they are negative or positive?
charged atom or molecule
Cations are positively charged
Anions are negatively charged
What is electrostatic pressure
Attractive force between molecules that are oppositely charged
OR repulsive force between molecules that are similar charged
what are ion channels vs leak channels
Ion channels
Specialized protein molecules that sit in the cell membrane.
Pore (hole) in them through which specific ions can enter or leave cells
Leak channel
An ion channel protein that is in the membrane and has a pore that is always open (e.g., potassium leak channel – only potassium is comfortable using this).
Monovalent cations and divalent cations
Monovalent cations: sodium (Na+) (more in extracellular space), potassium (K+) (more in intracellular space)
Divalent cations : calcium (Ca2+)(more in extracellular space), magnesium (Mg2+)(more in intracellular space)
What are the two proteins are responsible for setting up and maintaining the resting membrane potential of neurons
Sodium-Potassium transporter
Leak-Potassium Channel
What is Sodium-Potassium Transporter
Requires ATP, concentrates sodium and potassium outside and inside the cell, respectively
Pump Na+ atoms out of the cell and K+ atoms in.
Concentration gradients
K+ ions to be 30x more concentrated inside the cell than out
Na+ ions to be 15x more concentrated outside the cell than in.
These concentration gradients never change, ever, unless the cell dies
Membrane potential = 0 (no electrical charge difference)
What is a Leak-Potassium Channel?
Always open, the number of these channels largely determines the resting membrane potential
The cell membrane of neurons contains K+ leak channels, which are selectively permeable to K+.
If K+ was the only ion that could cross the membrane, the electrical potential of the membrane would settle at -90 mV, because this is when the force of diffusion encouraging K+ to leave is equal and opposite to the electrostatic pressure driving K+ in.
The resting membrane potential of most neurons is less negative than -90 mV because other ions can move across the membrane through other types of leak channels.
The more K+ leak channels a neuron has, the more permeable it will be to K+ relative to other ions and the closer its membrane potential will be to -90 mV.
Potassium leak channels are always open. Potassium can always flow through them (in either direction).
What are the three Proteins (Voltage-gated ion channels) that the action potential involves?
Voltage-gated sodium channel
Voltage-gated potassium channel
Voltage-gated calcium channel
What is the Voltage-gated sodium channel?
To initiate and propagate the action potential
These ion channels are found all over the axon, along its entire length.
Open – The gate opens whenever the membrane potential becomes less negative than -40 mV. The initial cause of this depolarized state is usually the activation of receptor protein ion channels that let in sodium
Have electrical charges on their doors, such that they open or close when the charge difference across the membrane is greater or smaller than some number
What is the Voltage-Gated potassium channel?
To restore the resting membrane potential
Ending the Action Potential
Voltage-gate K+ channels open when the membrane potential is more positive than 0 (no difference in charge between inside and outside of the cell).
The opening of the voltage-gated K+ channels helps bring the membrane potential back down to -70 mV
Voltage-gated potassium channels open in the middle of an action potential, when the membrane potential is around 0 mV.
What is the Voltage-gated calcium channel?
Located in the axon terminal, triggers the release of neurotransmitters
Synaptic transmission
Voltage-gated calcium channels open when the axon terminal becomes depolarized (i.e., in response to an action potential).
Calcium is 1000x more concentrated outside the cell than in.
The calcium that enters through these channels activates vesicle release machinery
When an action potential reaches the end of an axon (the axon terminal), it causes voltage-gated calcium channels to open. The influx of calcium into the axon terminal triggers the release of signaling molecules (neurotransmitters) into the synapse.
What is diffusion?
If there is a concentration gradient and no forces or barriers to prevent free movement of molecules, then molecules will move, on average, from regions of high concentration to regions of low concentration
Balancing Diffusion and Electrostatic energy
Neuronal membranes are filled with K+ leak channels. Given the ability to travel freely, K+ ions leave the cell on account of the force of diffusion
What are receptors?
All cell membranes are full of proteins that act as sensors (receptors). These proteins are sensitive to specific features of the extracellular environment.
For example, cells use proteins to detect and pull in nutrients from the extracellular space. (Nutrients include proteins, fats, sugars, vitamins and minerals.)
Neurons put receptor proteins on their dendrites to sense the external world.
What are sensors for detecting?
The presence of certain molecules (e.g., neurotransmitters)
Physical pressure (movement, touch)
Electrical pressure (voltage)
Temperature
pH (acidity, basicity)
Electromagnetic radiation (light)
What is depolarization?
Membrane potential of a cell becomes less negative than it normally is at rest
When positive sodium ions enter a cell through a receptor protein ion channel, they might depolarize a neuron from -70 to -60 mV
If this happens – they immediately close back up
Potassium leak channels are always open - potassium can flow in either direction through them
Action Potential
The opening of one Na+ channel allows Na+ ions to rush in, propelled by both diffusion and electrostatic forces.
This influx of Na+ depolarizes the membrane further, which in turn causes additional voltage-gated Na+ channels to open.
Soon there is an avalanche effect as all voltage-gated Na+ channels open causing the membrane potential to shoot up to +40mV
At the peak of the action potential, the membrane potential is +40 mV. All voltage-gated Na+ channels are now inactivated.
When voltage-gated potassium ion channels open, the outflow of K+ ions driven now by diffusion and electrostatic forces restore the resting membrane potential in about a millisecond.
What is the threshold for excitation?
The value of the membrane potential that must be reached to produce an action potential
What is synaptic transmission?
transmission of messages from one neuron to another via the release of signaling molecules (neurotransmitters) into the synapse. These signaling molecules activate receptor proteins on downstream neurons
What is a promoter
Region of DNA that initiates transcription of a particular gene
They indicate what kind of cells should read the gene and when
Typically located just before the gene
What are Neuroglia – or Glial Cells
Found al around neurons and physically encapsulate some parts of them
They help traffic nutrients and maintain molecular (ionic) stability in extracellular space
Support any functions of the Nervous system
Glial : Neuron = between 2:1 and 5:1
What is the glial cell astrocyte?
Glial cell providing physical support and cleans up debris in the brain through phagocytosis
Control chemical composition of surrounding environment and help nourish neurons
What is the glial cell microglia?
Smallest of glial cells
Provide immune system for the brain
Protect the brain from invading microorganisms
What is the glial cell oligodentrocyte?
Produce the myelin sheath that encapsulate axons
Sheath is a series of segments – not continuous
Exposed axon – Node de Ranvier
During the development of the CNS, oligodendrocytes form processes shaped something like canoe paddles
Each of the paddle-shaped processes then wraps itself many times around a segment of an axon and, while doing so, produces layers of myelin that make up part of the axon’s myelin sheath.
what is Saltatory conduction
The conduction of action potentials by myelinated axons
Action potential appears to jump from one Node of Ranvier to next – at each one the strength of the signal is regenerated with additional voltage-gated Na+ channels
Slow processing of pain and temperature
What is the impact of myelination
The only place where a myelinated axon comes into contact with extracellular fluid is at nod of Ranvier, where the axon is naked
In myelinated areas there are almost no ion channels and those that are there are of no consequences because there is no extracellular fluid outside the membrane
What are synapses/
Junction between axon terminal of the sending neuron and the cell membrane of the receiving neuron
Communication across the synapse is achieved by the release of a molecule from an axon terminal
What are neurotransmitters?
A molecule that can have a simple excitatory or inhibitory effect or a complex modulatory effect on the receiving neuron.
Synaptic vesicle
Contain molecules of neurotransmitter. They attach to the presynaptic membrane and release neurotransmitter into the synaptic cleft
synaptic cleft
The space between the pre- and postsynaptic membranes. It is filled with an extracellular fluid.
pre-synaptic membrane
The membrane of the terminal button (the sending cell). This is where neurotransmitter is released from.
post-synaptic membrane
The membrane of the receiving cell that is opposite the axon terminal.
What is electron microscopy
Allows us to see small anatomical structures (e.g. synaptic vesicles and details of cell organelles) using a special electron microscope.
What are ligands
Signaling molecules that bind to protein receptors
Most cell signaling and cell communication occurs through ligand-receptor interactions.
What are ionotropic receptors? (Neurotransmitter receptors)
ion channels
What are metabotropic receptors? (Neurotransmitter receptors)
G protein coupled receptors that can open ion channels through an intracellular signaling cascade.
Receptors can be found on the cell membrane (surface receptors) or inside the cell (intracellular receptors).
where are post-synaptic receptors located
on postsynaptic membrane
where are pre-synaptic receptors located
on presynaptic membrane.
where are extrasynaptic receptors located
near to but outside the synapse
Comunication between neurons
ligands
binding sites
post-synaptic receptor
ligand-gated ion channel/ionotropic receptor
what is a ligand
General term for a signaling molecule (chemical) that binds to the binding site of a receptor. Neurotransmitters are ligands
what is a binding site
Location on a receptor protein to which a ligand binds
what is a post-synaptic receptor
Receptor protein in postsynaptic membrane of a synapse that contains a binding site for a neurotransmitter
what is a Ligand-gated ion channel/Ionotropic receptor
A receptor that is an ion channel. The ion channel opens when the ligand (e.g., the neurotransmitter) binds to it
what is Enzymatic deactivation
Destruction of a neurotransmitter by enzyme after its release (example: destruction of acetylcholine by acetylcholinesterase
what is reuptake
Reentry of a neurotransmitter just liberated by a terminal button back through its membrane, thus terminating postsynaptic potential
what is a postsynaptic potential (Excitatory vs. Inhibitory)
Alterations in the membrane potential of a postsynaptic neuron, produced by neurotransmitter release into the synapse and receptor activation.
Excitatory – influx of positive sodium ions depolarize the cell
Inhibitory – influx of negative chloride ions hyperpolarize the cell
what is depolarization
Less negative than normal
Excitatory
When the membrane potential of a cell becomes less negative than it normally is at rest
influx of positive ions (Na+) can depolarize a neuron from -60 to -50 mV
what is hyperpolarization
Less positive than normal
Inhibitory
When the membrane potential of a cell becomes more negative than it normally is at rest
influx of negative ions such as Cl- can hyperpolarize a neuron from -60 to -70 mV
what is EPSP
Excitatory postsynaptic potential (EPSP)
Excitatory depolarization of postsynaptic membrane caused by neurotransmitter binding to a postsynaptic receptor protein.
Mediated by receptor proteins that open ion channels permeable to sodium. (Making the membrane more permeable to sodium will depolarize the cell.)
Brief depolarization of the membrane potential, typically caused by neurotransmitter activation of ionotropic receptors that let in positively charged sodium ions.
What is IPSP
Inhibitory postsynaptic potential (IPSP)
Inhibitory hyperpolarization of postsynaptic membrane caused by neurotransmitter binding to a postsynaptic receptor protein.
They are mediated by receptor proteins that open ion channels permeable to chloride (Making the membrane more permeable to chloride will hyperpolarize the cell.)
Brief hyperpolarization of the membrane potential, typically caused by neurotransmitter activation of ionotropic receptors that let in negatively charged chloride ions
What is neural integration
The interaction of the excitatory and inhibitory synapses on a particular neuron
When EPSPs and IPSPs occur at the same time, the influx of negatively charged chloride ions diminish the impact of the positively charged sodium ions. IPSPs decrease the likelihood that the cell will fire.
What is a postsynaptic potential
Can be depolarizing or hyperpolarization
Receptor – determines the direction of the postsynaptic potential
Ex. Some serotonin receptors sauce exhibitory and others cause inhibitory potentials
what is an ionotropic receptor
A neurotransmitter receptor that is an ion channel.
The properties of the pore of the ion channel (the hole) will determine if it causes EPSPs or IPSPs (i.e., if it lets in sodium or chloride ions)
what is a receptor protein
Protein that is sensitive to and capable of communicating some signal.
what is an ionotropic receptor protein
Neurotransmitter binds and can change shapes to accept/bind
Turn towards IONS to mediate their effect
A receptor protein that is an ion channel.
The properties of the pore of the ion channel (the hole) determine if it will produce EPSPs or IPSPs (i.e., if it lets in sodium or chloride ions).
The direct effect of ionotropic receptor activation is always an immediate change in the permeability of the membrane to specific ions (i.e., whatever ions pass through the receptor).
what is an metabotropic receptor protein
Proteins but not ion channels – they also change shapes but they don’t have automatic reaction like the ionotropic receptors
Turn towards METABOLISM to mediate their effect
A receptor protein that is not an ion channel. These receptors typically trigger an intracellular signaling cascade that involves g proteins, which can produce a variety of cellular effects such as a change in gene expression or the opening/closing of g protein-gated ion channels. The effects of metabotropic receptor signaling can be quite large, but they are often delayed (because they rely on signaling cascades and diffusion).
Metabotropic receptor activation can cause the opening of many ion channel
what is a g protein
G proteins are a family of intracellular proteins that are involved in intracellular signaling cascades.
All G protein coupled receptors are METABOTROPIC
“G proteins” are proteins that use GTP molecules instead of ATP molecules for their energy to perform chemical reactions
what happens when a g protein binds to GTP
it turns it “ON” and can trigger chemical reactions
A g protein turns GTP into GDP. This process turns the protein “OFF”
G proteins have a hard time letting go of GDP
how do they do it?
They do so by finding an activated metabotropic receptor and use the intracellular side of an activated metabotropic receptor to pry off their GDP molecule.
After prying off the GDP molecule, they bind to another GTP molecule and the process starts over again
What is a g protein-gated ion channel and how does it work
Some ion channels are gated by g proteins. They all use the GTP molecule for energy.
Generalized illustration of a metabotropic GPCR receptor causing ion channel opening
Neurotransmitter binds to a metabotropic receptor.
Activated g proteins transmit the message intracellularly.
Some ion channels are gated (directly or indirectly) by activated g proteins.
G protein signaling cascades can affect multiple downstream processes including
opening g protein gated ion channels
changes in gene transcription
secretion of substances from the cell
really anything the cell wants.
Where do synapses form
Between axon terminals
Dendrites (dendritic shafts) - cause action potential
Dendritic spines – cause action potential
The soma (cell body) - cause action potential
Other axon terminals (axoaxonic synapses)
What are axoaxonis synapses
Regulate amount of neurotransmitter that the second neuron will release when it has an action potential
what is presynaptic inhibition
Axoaxonic synapse can HYPERPOLARIZE the axon terminal of the downstream neuron, so that its voltage-gated calcium channels WILL NOT OPEN at all or for very long when an action potential arrives.
The net effect is to REDUCE neurotransmitter release from the red cell when it has an action potential.
what is presynaptic facilitation
Axoaxonic synapse can DEPOLARIZE the axon terminal of the downstream neuron, so that its voltage-gated calcium channels are MORE LIKELY TO OPEN when an action potential arrives.
The net effect is to INCREASE neurotransmitter release from the red cell when it has an action potential.
what are autoreceptors
A receptor located on presynaptic membrane that gets activated when the cell releases its own neurotransmitter.
They are gated by the neurotransmitter that the cell releases.
They are generally metabotropic and inhibitory.
Main source of presynaptic inhibition.
what is a post-synaptic receptor
A receptor located on the receiving neuron (the one that is not releasing the neurotransmitter).
Anatomical directions
neuraxis
anterior
posterior
superior
inferior
rostral
caudal
dorsal
ventral
lateral
medial
transverse plane
sagittal plane
horizontal plane
Neuraxis – imaginary line that runs along the length of the CNS
Animals and Human head
Anterior – in front
Posterior – behind
Superior – above
Inferior – below
Rostral – towards the beak
Caudal – towards the tail
Dorsal – towards the back
Ventral – towards the belly
Human spinal cord
Lateral – away from the midline
Medial – towards the midline
“Geography” of the brain
Transverse plane (frontal section, cross section, coronal section)
Sagittal plane – A mid-sagittal cut means the exact middle (between the eyes)
Horizontal plane – looking down at horizontally cut brain
Contralateral
Ipsilateral
Superfacial
Deep
Proximal
Distal
Brain Nuclei
Contralateral – structures on the opposite side of the body
e.g., the motor cortex controls movements of the contralateral hand.
Ipsilateral – structures on the same side of body
e.g., taste information is processed ipsilaterally, which means that taste receptors on the left side of your tongue are processed by your left cerebral hemisphere. Taste and smell are the only sensory systems that do not have contralateral organization.
Superficial – located close to the surface, close to the exterior of the animal
Deep – located far away from the surface, deep in the interior of the animal
Proximal – nearby
Distal – far away
Brain nuclei – in the brain, the word nuclei means a collection of neurons that are clustered together that all work together to serve some function.
E.g., there are many different brain nuclei in the hindbrain. One controls breathing, another controls vomiting, etc.
Central Nervous Systen
CNS
Everything in the brain AND spinal cord
Myelin created by oligodendrocytes
A neuron located in the CNS is considered an interneuron
Interneuron is only used for CNS neurons whose axon STAYS LOCAL (it only makes synapses on nearby neurons).
The term projection neuron to used when the axon of a cell goes outside the area where its soma is located
Peripheral Nervous system
PNS
Any part of the nervous system outside the brain and the spinal cord
Myelin created by Schwann Cells
PNS communicates with the rest of the body with NERVES (cranial and spinal nerves)
Axons of motor neurons:Efferent or Afferent? (What does that mean)
EFFERENT fibers – fibers that bring information AWAY from (the CNS), the OUTPUTS
Motor neurons control muscle contraction and gland secretion. The soma of motor neurons is located within the spinal cord (the CNS).
Axons of sensory neurons: Efferent or Afferent? (What does that mean)
AFFERENT fibers – fibers that bring information TOWARDS… (the CNS), the INPUTS.
Sensory neurons detect changes in the external and internal environment. They send this information to the CNS.
These nerves are part of PNS, which sends sensory information to the CNS and effector information away from the CNS (targeting muscles and glands throughout the body). How many are there
31 pairs of spinal nerves attach to the spinal cord (like 1 pair per vertebrae)
12 pairs of cranial nerves attach to the ventral surface of brain
What is the job of cranial nerves
All the cranial nerves (except the 10th) serve sensory and motor functions of head and neck region
what is the job of the 10th cranial nerve
The 10th cranial nerve is called the vagus (“wandering”) nerve because its branches wander throughout thoracic and abdominal cavities. It regulates functions of the heart, lungs, upper digestive track, and other organs in that area.
what are the two systems within the PNS
Somatic NS and Autonomic NS
Describe the Somatic NS
Interacts with external environment
Afferent nerves – carry sensory signals from eyes, ears, skin, etc TO CNS
Efferent nerves – carry motor signals FROM CNS to skeletal muscles
Describe the Autonomic NS
Regulates body’s internal environment
Afferent nerves – carry sensory signals from internal organs, etc TO CNS
Efferent nerves – carry motor signals FROM CNS to internal organs
The efferent ANS consists of two anatomically separate systems:
Sympathetic and parasympathetic divisions
What is the Sympathetic division of the Autonomic NS
Part of efferent autonomic nervous system that primes the body for action, particularly in life threatening situations (e.g., it mediates the flight-fight-freeze response when animals are threatened).
What is the Parasympathetic division of the Autonomic NS
Part of efferent autonomic nervous system that supports activities that occur when the body is in a relaxed state and all is well. It is generally involved with increasing the body’s energy stores (i.e., digestion).
Its functions also include sexual arousal, defecation, urination, and salvation.
For simplicity, people often say the parasympathetic system is involved in “feed and breed” and “rest and digest” activities.
What is the blood-brain barrier
Semipermeable barrier between the blood and the brain
The blood capillaries that pass through the brain and spinal cord do not have gaps in them. This property is known as the blood brain barrier.
Interstitial fluid in the body and brain
Outside the brain and spinal cord, all extracellular fluid comes from blood.
Blood vessels in the body have small holes in them, which allows the liquid part of blood (blood plasma) to continually leak out.
What is Lymph? What does it do?
The blood that leaks out becomes lymph
Lymph – the extracellular fluid of the body.
Flows around cells providing nutrients and collecting waste.
It is then collected into lymph vessels and brought to lymph nodes / lymph organs.
These structures detect and destroy any invading organisms or foreign particles, and then they return the lymph back to the blood to start the process again.
Rather than letting blood leak out, the brain simply makes its own extracellular solution by actively picking out exactly what it needs from the blood. The solution it makes is called cerebrospinal fluid (CSF).
What are Meninges? What are the three types of meninges
Tough, protective connective tissues that surround the brain
dura matter
arachnoid membrane
pia matter
what is dura matter
The outer layer: thick, tough, unstretchable tissue
what is the arachnoid membrane
The middle layer: soft and spongy and has a web-like appearance
what is the pia matter
The third layer that sits closest to the brain: This layer and the space above it has blood vessels in it.
What is the subarachnoid space (between the arachnoid membrane and pia mater) filled with?
cerebrospinal fluid (CSF) and blood vessels.
What is the spinal cord
A long conical structure approximately as thick as an adults little finger.
Principle function – collect sensory information to be passed on to the brain and distribute motor fibers to effector organs throughout the body (glands and muscles)
Has a certain degree of autonomy from the brain: various reflective control circuits are located there.
What is Neurogenesis
Production of new neurons
Neural progenitor cells produce neurons (and glia) when they undergo asymmetrical cell division.
Human neurogenesis largely stops four months after conception when neural progenitor cells undergo apoptosis.
What is apoptosis
Process of programmed cell death that occurs in a multicellular organism
Apoptosis is a highly regulated and controlled form of cell suicide that ensures a dying cell does not cause problems for its neighbors.
Human neural progenitor cells undergo apoptosis 125 days after conception
Anatomical divisions of the brain
What are the three major divisions in the brain
Forebrain
Midbrain
Hindbrain
Anatomical divisions of the brain
What are the five principal structures of the Forebrain
Cerebral cortex
Basal ganglia
limbic system
Thalamus
Hypothalamus
Anatomical divisions of the brain
What are the two Principal structures of the Midbrain
Tectum
Tegmentum
Anatomical divisions of the brain
What are the threeprincipal structures of the Hindbrain
Cerebellum
Pons
Medulla oblongata
What is the cerebellum
Known as the “LITTLE BRAIN”
Plays an important role in motor control.
The cerebellum does not initiate movement, but it contributes to its coordination, precision, and accurate timing.
Integrates sensory information and motor commands to exert a coordinating and smoothing effect on movement (and cognition).
Plays an important role in motor learning, particularly when parts of the body grow and change (which necessitate adjustments in sensorimotor integration).
What is the result of Cerebellar damage
Cerebellar damage primarily results in jerky, poorly coordinated, exaggerated movements. Extensive cerebellar damage makes it impossible even to stand.
What is the pons
Large bulge in the brain stem that relays information between the cerebrum and cerebellum.
Contains part of the reticular formation as well as several cranial nerve nuclei, which participate in hearing, balance, taste, and sensations and movements of the face.
What is the medulla oblongata
Most caudal part of the brain stem. It contains a collection of brain nuclei that regulate different autonomic (involuntary) functions, such as heart rate and blood flow, breathing, vomiting, sneezing, etc.
Area postrema is a famous part of the medulla, as the blood–brain barrier is noticeably weak here.
The medulla also contains part of the reticular formation, which plays an important role in sleep and arousal.
What is the tectum
“roof”
Appear as two pairs of bumps on the dorsal surface of the midbrain
Top 2 bumps – superior colliculi
Involved in orienting the animal to things seen in peripheral vision
Bottom 2 bumps – inferior colliculi
Involved in orienting to unexpected sounds
What is the tegmentum
Several structures that coordinate and motivate complex species-typical
Some areas process pain and orchestrate behavioral responses to threats
What is the Cerebral cortex
Sensory information enters conscious awareness.
It is where our understanding of the world is formed and where we decide how to purposefully move in the world.
The cerebral cortex is not made up of distinct nuclei (except in birds). Rather, it is a multi-layered structure (6 layers in mammals, 3 layers in reptiles).
Neurons are interconnected between layers in a way that gives rise to cortical columns, which are thought to be partially distinct functional units.
The cerebral cortex is the surface of the brain, which is highly convoluted with what?
sulci (small grooves)
fissures (large or major grooves)
gyri (ridges between sulci or fissures).
These convolutions increase the surface area of the cerebral cortex.
The outermost portion of the cerebral cortex is called gray matter. The color is because of the high concentration of cell bodies there.
The white matter (beneath the gray matter) has a large concentration of myelinated axons. There are very few neurons in this area
What are different view of the cerebral cortex
Dorsal, Lateral, Ventral and Medial view
Longitudinal fissure - separates the two hemispheres
Lateral fissure - separates frontal from temporal lobes
Central sulcus - provides a good landmark separating the rostral and caudal divisions of the cerebral hemisphere
Although cerebral hemisphere have different functions, perceptions and memories are unified. This is because of what
The corpus callosum
large band of axons connecting corresponding parts of association cortex for left and right hemisphere.
What are the 4 lobes in the cerebral cortex
Frontal lobe
Parietal lobe
Occipital lobe
Temporal lobe
What is the frontal lobe in the cerebral cortex responsible for?
controls movement
What is the parietal lobe in the cerebral cortex responsible for?
touch information
What is the occipital lobe in the cerebral cortex responsible for?
visual information
What is the temporal lobe in the cerebral cortex responsible for?
auditory information
What does the insular cortex in the cerebral cortex focus on
taste
what does the piriform cortex in the cerebral cortex focus on
smell
What are the primary cortical areas in the cerebral cortex
primary motor cortex
somatosensory cortex
primary auditory cortex
primary visual cortex
What is the primary motor cortex in the cerebral cortex in charge of
Frontal lobe
Motor neurons synapse in the spinal cord
What is the somatosensory cortex in the cerebral cortex in charge of?
Parietal lobe
Touch information enters cerebral cortex
What happens if somatosensory cortex is damaged?
If this damaged - you know you are touching something but you do not know what
What is the primary auditory cortex in the cerebral cortex in charge of?
Temporal lobe
Auditory information enters cerebral cortex
What happens if primary auditory cortex is damaged?
If this damaged - you hear something but do not know what (ex. You hear a dog barking but don’t recognize it is a dog)
What is the primary visual cortex in the cerebral cortex in charge of?
Occipital lobe
Visual information enters the cerebral cortex
What happens if the primary visual cortex is damaged?
If this damaged - you do not recognize faces (not even family)
What is the sensory association cortex in the cerebral cortex
Perception takes place and memories stored
Areas of sensory association cortex nearest to primary sensory areas receive information from one only sensory system
What is the premotor cortex in the cerebral cortex
Adjacent to sensory association cortex
Where movements are planned
What is the basal ganglia and what does it do?
Previously called the primitive « reptilian » brain
Collection of nuclei in the forebrain
Regulate intentional movements, motivation, reinforcement learning and habits
Where do inputs to the basal ganglia come from
Come from all over the forebrain especially the frontal lobe
Where do outputs to the basal ganglia come from
Some descend to midbrain and hindbrain nuclei that regulate movements
Others descend in cerebral cortex (via thalamus) that regulate sensory processing and decision making
Many neurological disorders (classical « movement» disorders) are associated with basal ganglia dysfunction - True or False
TRUE
What is the limbic system
Collection of subcortical brain areas that regulate emotions and the formulation of episodic memories
what are the principle areas of the limbic system
Hippocampus
Critical for explicit memory formation
Hidden in the temporal lobe
Amygdala
Critical for emotional processing especially for fear
Hidden in the temporal lobe
Cingulate cortex
Large area that overlies the corpus callosum
Cingulate = encircling
This region interconnects with many lambic areas of the brain
What is the thalamus and its functions
Bilateral structure that is divided into several nuclei, many of which relay ascending sensory information to different regions of the cerebral cortex.
Ex; visual information from the eye passes through the thalamic lateral geniculate nuclei, whereas sound information from the ear passes through the thalamic medial geniculate nuclei.
Many nuclei of the thalamus have widespread cortical projections.
What is the hypothalamus and its functions
Bilateral structure made up of several nuclei that regulates ANS activity
Involved in behaviors that directly relate to survival (i.e. the four F’s: feeding, fighting, fleeing and mating)
Involved in behaviors that directly relate to survival (i.e. the four F’s: feeding, fighting, fleeing and mating)
One of the most important functions of the hypothalamus is to link the nervous system to the endocrine system (release of hormones into the blood stream) via the pituitary gland.
What is a hormone
chemical substance that is released by an endocrine gland and that has effect on target cells in other organs
What is the endocrine gland
gland that secretes chemical signals (hormones) into the bloodstream. Much of the endocrine system is controlled by hormones produced by cells in hypothalamus
What is a receptor protein
A protein that senses some signals
What is an ionotropic receptor protein
A receptor that is an ion channel
Activation has an immediate consequence on the membrane potential, causing a depolarization or hyper polarization (more or less spiking)
What is an metabotropic receptor protein
A receptor that is not an ion channel
Typically signal through G proteins on the intracellular side.
Activation can produce any effect from a change in the membrane potential to a change in gene expression
What is Glutamate neurotransmitter and its functions
Main EXCITATORY neurotransmitter
All ionotropic glutamate receptors let sodium in
Typically excitatory - the gas pedal
Ionotropic glutamate receptors let in sodium ions causing excitatory post-synaptic currents (ESPCs) and membrane depolarization
what are agonists and antagonists of glutamate
Agonists
Often cause seizures and excitotoxicity
Antagonists
Dissociative anesthetic (ketamine, PCP)
What is GABA neurotransmitter and its functions
Main INHIBITORY neurotransmitter
All ionotropuc GABA receptors let chloride in
Typically inhibitory - the brakes
Ionotropic GABA receptors let in chloride ions, causing inhibitory post-synaptic currents (IPSCs) and membrane hyper polarization
what are agonists and antagonists of GABA
Agonists
Anaesthetics, anticonvulsants, muscle relaxants, sleeping pills, anti-anxiety (alcohol, barbiturates, benzodiazepines)
Antagonists
Often cause seizures
What are main neuromodulators and what do they do
Dopamine
Norepinephrine
Acetylcholine
Serotonin
These neurotransmitters primarily act on metabotropic receptors and tend to exert a modulatory influence on cell activity *in contrast to glutamate and GABA, which often causes fast EPSPs or IPSPs via their respective ionotropic receptors)
Are released from small collections of neurons that send their axons out widely
Why are they called neuromodulators
Most of their receptors are g-protein coupled receptors, not ion channels
They typically don’t produce simple excitatory or inhibitory effects in CNS
They can diffuse short distance outside of the synapses and influence the activity of neighboring neurons.
What are types of neurotransmitters
conventional neurotransmitters
neuropeptides
lipid-based signaling molecule
What are conventional neurotransmitters? Where are they synthesized and held? Ionotropic or metabotropic?
Mostly amino acid derivatives (modified amino acids)
Main players - glutamate, GABA, Dopamine, Norepinephrine, Acetylcholine, Serotonin
Synthesized locally in axon terminals
Usually secreted from small synaptic vesicles that dock very close to the site of Ca+ entry in axon terminal
Generally active ionotropic AND metabotropic receptors
Typically recaptured after secretion and REUSED
Usually binds receptors directly across the synapse. Even when they diffuse, they only influence activity of neighboring neurons
What are neuropeptides? Where are they synthesized and held? Ionotropic or metabotropic?
Short string of amino acids (ex. A protein formed with only 10-30 amino acids)
Ex. Of >70 : oxytocin, vasopressin, enkephalin, prolactin, NPY, ghrelin, CRH
Synthesized in cell soma, transported down axon while undergoing additional processing and release just once
Usually secreted from large dense core vesicles that dock a ways back from the site of Ca2+ entry in the axon terminal
Only activates METABOTROPIC receptors
No synaptic recycling occurs of either the neuropeptides or their immediate precursors
May diffuse long distances long distances and exert action at a distance (non-synaptic communication)
What are Lipid-based signaling molecules? Where are they synthesized and held? Ionotropic or metabotropic?
Ex. Cannabinoids, anandamide, arachidonoyl glycerol
synthesized and released on demand as needed
Secreted in non-vesicular manner, typically from postsynaptic neurons
Only activates METABOTROPIC receptors, typically located on the presynaptic axon terminal
Monoamine Neuromodulators
Serotonin, dopamine, norepinephrine and epinephrine are all monoamines
catecholamines
Dopamine, norepinephrine and epinephrine are further classified as catecholamines as they have exceptionally similar chemical structures
epinephrine and norepinephrine are synthesized from dopamine
indolamines
serotonin
How does venom in animals, like snakes or spiders, cause paralysis or excessive muscle contrations?
contain substances that interfere with neurotransmitter signaling.
Many interfere with neurotransmitter signaling at the neuromuscular junction
What is Acetylcholine?
Neurotransmitter
What does Acetylcholine do in the CNS?
Primarily acts as a neuromodulator often as axoaxonic synapses
What does Acetylcholine do in the PNS? Describe it in terms of motor and sensory neurons
Released by motor neurons at the neuromuscular junction where it activated the fast excitatory ionotropic receptors on muscle cells that cause muscle contraction.
Motor neurons
Generally release ACETYLCHOLINE as their main neurotransmitter
Sensory neurons
Generally release GLUTAMATE as their main neurotransmitter
What is the difference between Black Widow Spider venom and Botulinum toxin (Botox)
BWSV
Poison triggers the release of acetylcholine
Botox
Produced by bacteria that grow in improperly canned food.
Acetylcholine system agonist since it prevents the release of acetylcholine
Causes muscle paralysis
What is Neostigmine ?
Drug that inhibits the activity of acetylcholinesterase
Acetylcholinesterase – enzyme that breaks down acetylcholine in synaptic cleft
Causes acetylcholine to stay around longer in synapses causing more muscle contraction
What is Myasthenia Gravis?
Hereditary autoimmune disorder
Your own immune system attacks their healthy acetylcholine receptors
What is a receptor AGONIST?
INCREASES activity of postsynaptic receptor protein
What is a receptor ANTAGONIST
DECREASE activity of postsynaptic receptor protein
What is a direct (angonist or antagonist)
Drugs that affect postsynaptic receptor activity by directly binding to postsynaptic receptors
What is a indirect (angonist or antagonist)
Drugs that affect postsynaptic receptor activity in an indirect manner (proteins they bind to are not postsynaptic receptors)
Describe an Antipsychotic (neuroleptics)
Direct dopamine receptor antagonists (receptor blockers)
Class of drug used to treat psychosis
What is Psychosis
Psychosis is an abnormal condition of the mind that results in difficulties determining what is real and what is not real
Affects approximately 1% of the population
Do antipsychosis drugs bind to more than one recpetor?
YES
What receptors does an antipsychosis drug affect and how?
They all directly block dopamine D2 receptors
Inhibitory metabotropic receptor expressed by neurons all over the brain
What are Direct serotonin receptor agonists (receptor activators)
Some drugs are use to treat mental illnesses and others are used recreationally
Most popular drugs are the ones that directly activates serotonin 2A receptors (inhibitory metabotropic receptors expressed by neurons all over the brain)
Not all drugs that activate serotonin 2A receptors cause hallucinations
Some 5HT-2A receptor agonists cause massive hallucinations
What 4 drugs directly activate serotonin 2A receptors
Mescaline (hallucinogen)
Psilocybin (hallucinogen)
LSD (hallucinogen)
Lisuride (not a hallucinogen)
What do the 4 drugs that directly activate serotonin 2A receptors do when they bind to a metabotropic receptor? What activates this? What is activated?
When these agonists bind and activate this metabotropic receptor, they launch an intracellular signaling cascade that starts with the g protein
Serotonin normally activates this receptor in this manner
When hallucinogenic drugs bind to this receptor, we also see activation of the g protein
Hallucinations result from serotonin 2A receptor activation of G proteins. But we do not yet know why this g protein signaling cascade causes hallucinations
What is biased Agonism
Metabotropic receptor ligand causes receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
What is competitive binding? Describe it in terms of competitive agonist and antagonist.
A competitive AGONIST acts similarly to the endogenous neurotransmitter.
It activates the receptor by binding where the neurotransmitter normally binds.
Direct receptor agonists can be full agonists or partial agonists
A competitive ANTAGONIST attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor.
Competitive antagonists are full antagonists.
What is non-competitive binding? describe it in terms of non-competitive agonist and antagonist
When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand it is called non-competitive binding. It is possible for a neurotransmitter to bind on one site of a receptor while a drug binds on another.
Non-Competitive AGONIST
Fully or partially activates the receptor
Non-Competing ANTAGONIST
Fully blocks receptor activation.
It doesn’t compete for the neurotransmitter binding site.
It “wins” without competing by binding to an alternative site
What is an allosteric modulator?
Non-competitive drugs that only influence receptor activity when the neurotransmitter is also bound to the receptor.
What is the difference between a negative allosteric modulator and a positive allosteric modulator
Negative
Reduce the effect of the primary ligand.
Positive
Amplify the effect of the primary ligand.
What is Parkinson’s disease
Neurological disorder
Characterized by tremors, rigidity of limbs, poor balance, and difficulty initiating movements.
Caused by the degeneration (death) of dopamine neurons in the midbrain.
What is used against Parkinson’s diesase
The amino acid L-Dopa is often used as a drug to treat Parkinson’s disease because it increases dopamine production in the brain and thus acts as an indirect dopamine receptor agonist.
Where are conventional neurotransmitters made?
in the axon terminals
made from precursor molecules (generally from amino acids).
What are precursor molecules
Can be administered as drugs since
They can increase the amount of neurotransmitter that is made and released. In such cases, the precursors acts as receptor agonists.
The synthesis of neurotransmitter from precursor molecules is controlled by enzymes. How do some antagonists work?
Some antagonists work by blocking these enzymes, thus reducing production of the neurotransmitter so there is less in each vesicle
Once made, neurotransmitters are packaged into synaptic vesicles. How do some antagonists work?
Some antagonists work by blocking the transporter proteins that package neurotransmitter into vesicles. When this occurs, the synaptic vesicles can remain empty, so nothing is released when they fuse with the presynaptic membrane
Many proteins in the axon terminal regulate synaptic vesicle exocytosis (i.e., vesicle fusion with the presynaptic membrane). How do some antagonists and agonists work?
Some antagonists work by blocking the vesicular release machinery, so no neurotransmitter is ever released (e.g., botox).
Some agonists work by activating the vesicular release machinery, causing neurotransmitter release (e.g., black widow spider venom).
The clearance of neurotransmitters from the synapse is controlled by reuptake transporter proteins and enzymatic deactivation. How do some angonists work?
Some agonists block the enzymatic deactivation of neurotransmitter in the synaptic cleft (e.g., neostigmine).
Some agonists block neurotransmitter reuptake proteins. Some agonists can even reverse the reuptake transporters, so that neurotransmitter is pushed into the synapse as soon as it is made (without ever getting packaged into a synaptic vesicle).
What are the drugs that block the reuptake of catecholamine neurotransmitters and the dopamine & norepinephrine reuptake transporters?
Methylphenidate, Cocaine
What are the drugs that reverse catecholamine reuptake transporters, causing dopamine and norepinephrine to flow out of the axon terminal before being packaged into a vesicle (action potential-independent, non-vesicular release)?
Adderall, Crystal meth
[Ecstasy (MDMA) does a similar thing to all the monoamine reuptake transporters (i.e., causes them to run backwards).]
What are drugs and how can they be categorized?
Drugs are exogenous chemicals that at low doses significantly alter the function of certain cells.
Drugs can be categorized in different ways:
According to their behavioural effects (e.g., upper, downer, stimulant)
According to their physiological effects (e.g., action potential blocker)
According to their actions on specific proteins (e.g., serotonin reuptake blocker)
According to their effects on postsynaptic receptor activity
Heroin
Easily crosses the blood-brain barrier
An enzyme in the blood makes it VERY LIPID/ fat soluble
Morphine
Less easily crosses the blood-brain barrier
Less lipid soluble
Does Imodium Anti-Diarrheal cross the blood brain barrier
Does not cross the blood-brain barrier
What do
Heroin
Morphine
Imodium Anti-Diarrheal
have in common
All very strong opiates (opioids)
All cause constipation
3 main types of opioid receptors
All inhibitory, metabotropic receptors found throughout the body and the brain
Normally get activated by endogenous opioid peptides that function as hormones in the body and as neuropeptides in the CNS
What is tolerance
When a drug effect gets smaller with repeated administration.
The body becomes used to the drug and actively counteracts its effects.
After tolerance develops, in the absence of the drug the user will suffer withdrawal symptoms, which are opposite the effects of the drug (e.g., euphoria vs dysphoria; constipation vs diarrhea).
what is sensitization
Occurs when a drug effect becomes larger with repeated use
what is placebo
Occurs when a drug effect becomes larger with repeated use
describe computerized tomography (CT) Scan
STEP 1
Relatively cheap and fast
The resolution is not great for soft tissue like brain.
A computer assisted X-ray procedure used to take a “photograph” of the brain.
Patient lies with his or her head positioned in the centre of a large cylinder.
X-ray beam (i.e., high energy electromagnetic radiation) is projected through the head to an X-ray detector
X-ray beam is delivered from all angles.
A computer translates the information received from the X-ray detector into a series of pictures of the skull and brain.
Describe Magnetic Resonance Imaging (MRI)
STEP 2
Uses strong magnetic fields (instead of X-rays).
The patient lies in the centre of a large cylinder (like CT Scan)
When a strong magnetic field is applied to the body, the spin of every hydrogen atom proton assumes a particular direction inline with the magnetic field.
Radiofrequency waves (i.e., low energy electromagnetic radiation) are administered to the body.
This energy is absorbed by protons, changing the direction of their spin.
These protons then emit their own radio waves when their spin immediately flips back to that determined by the magnet
By triangulating where the emitted radio waves came from, the scanner can provide an estimate of the relative density of protons (hydrogen atoms) in each area of the body.
describe Diffusion Tensor Imaging (DTI)
STEP 3
A variation of the MRI technique
Measures the direction and speed of the diffusion of water molecules
Used to identify axon tracts
Colors indicate the direction of water molecule diffusion
describe Functional Magnetic Resonance Imaging (fMRI)
fMRI uses a rapid series of MRI scans
The amount of oxygen in blood distorts the local magnetic field.
With a series of MRI scans, it is possible to detect changes in blood oxygenation, which reflects blood flow and correlates with neural activity.
When a brain area is active, blood flow to that region quickly increases (~5s lag).
Popular BECAUSE:
Doesn’t involve needles
Doesn’t involve surgery
Doesn’t involve radioactivity
It provides both structural and functional information with decent spatial resolution (1 to 5 mm) and temporal resolution (several seconds).
Describe Positron Emission Tomography (PET)
PET scans involve injecting a person with a radioactive compound.
Radioactive sugar molecules (like 2-DG) are commonly used to detect changes in energy use in the brain.
Sugar broken down too quick and used by cells so was hard to track (slightly modified sugar)
2-DG is similar to glucose, in that it is taken up by energy consuming cells in the body.
However 2-DG is not broken down as easily as sugar is, so it stays around for hours.
Disadvantages of PET scans
The scanner identifies where radioactive 2-DG molecules are located over time.
The MAIN DISADVANTAGE of PET scanners is their operating COSTS
For safety reasons, the radioactive molecules are designed to decay rapidly (over hours), thus they have to be made on site the morning of the experiment.
PET images of radioactive L-Dopa given to healthy people and people with Parkinson’s disease.
Radioactive L-Dopa is picked up by dopamine neurons, converted into dopamine, and released as normal. There are fewer dopamine neurons in the brains of people with Parkinson’s disease.
PET is also used to measure changes in the expression levels of neurotransmitter receptors across weeks. These studies use radioactive agonists/antagonists.
What is a Macroelectrodes (EEG)
An electroencephalogram is a measure of electrical activity in the brain that uses macroelectrodes (metal discs) attached to the scalp.
Records the summed population-level activity of millions of neurons
Can be used as a diagnostic tool – specific patterns of
EEG activity are associated with different states of:
Consciousness
Stages of sleep
Types of cerebral atrophy
Lesion study
If you want to know what an area of the brain is good for, lesion it in an animal and see how their behavior changes
Involves the removal or destruction of a portion of the brain
Presumably, the functions that can NO LONGER be performed following the surgery are the ones the brain region NORMALLY controls.
How do scientists create lesions in the brain
Radiofrequency Lesions
Excitotoxic lesion
SHam lesion
reversible lesion
What is Radiofrequency Lesions
Radiofrequency Lesions
Small lesions can be made by passing radiofrequency current THORUGH A METAL WIRE that is insulated everywhere but the tip.
This ELECTRIC CURRENT produces heat that burns cells around the tip of the wire.
The size and shape of the lesion is determined by the duration and intensity of the current.
A DOWNSIDE to this approach is that axons just passing through will also be burned.
What is sham lesion
“Placebo” procedure that duplicates all steps of producing brain lesion except for one that actually causes extensive brain damage
what is excitotoxic lesion
Brain lesion produced by intracerebral injection of a glutamate receptor agonist, such as kainic acid.
These drugs cause so much excitation (and calcium influx) that the affected neurons often undergo apoptosis, while axons passing through (fibers of passage) are usually spared.
What is a reversible lesion
A temporary brain “lesion” can be achieved by injecting drugs that block or reduce neural activity in a given region.
Common drugs include
Voltage-gated sodium channel blockers (stops all action potentials)
GABA receptor agonists (which hyperpolarize cell bodies)
What are microelectrodes
Most direct measurements of neural activity
Made with thin metal wires placed in the brain
They have a fine tip that can record electrical activity of individual neurons (single-unit recordings)
Record every action potential from a given neuron
What are CHRONIC electrical recordings
made over an extended period of time
what are acute recordings
Made over a relatively short period of time
Often during surgery when the animal is anesthetized
What is electrical stimulation
Involves passing an electrical current through a wire inserted in the brain.
Affects EVERYTHING in the area
Cell bodies and fibers of passage
Some electrical simulation patterns
Often very high frequencies
Tend to produce the same behavioral effects as lesioning in the area
What is chemical stimulation
Achieved with DRUGS
In rodents: Drugs administered through guide cannula (hollow tube) implanted in particular brain area
Anesthetics can be injected to shut down all neural activity
Receptor agonist/antagonist can be used
Should not affect fibers of passage since there are no neurotransmitter receptors on the membrane in the middle of an axon (axons passing through)
What is optogenetics
The use of light to control neurons which have been made sensitive to light through the introduction of foreign DNA.
Foreign DNA encodes light-sensitive proteins known as opsins
What are opsins
Proteins that are sensitive to light
Opsins in our eyes are metabotropic receptors that operate with a 30-millisecond delay
Opsin used for optogenetics are often ion channels that open and close instantly in response to light
Original ones were discovered in bacteria in different parts of the world
Can design and modify opsins for research purposes
What is the point of optogenetics and using opsins
Lots of different photosensitive ion channels evolved in bacteria and algae.
POPULAR EXCITATORY one named channelrhodopsin-II (ChR2)
Permeable to sodium ions
Depolarizes neurons
Causes spiking when activated by blue light.
Other opsins, like IC++
Designed by humans
Inhibitory
Light sensitive ion channels (pass chloride and hyperpolarize neurons when activated by blue light)
what is a virus
Type of DNA delivery system
Normally replicate by injecting viral DNA into a host organism
Contains instructions on how to make more virus.
We know how to remove the DNA from a virus – renders the virus “replication-deficient”. Can add foreign DNA to the virus (DNA that encodes – ex. fluorescent proteins or optogenetic proteins.)
Once the virus gets its DNA into the infected cell’s nucleus, that cell will start to transcribe it and make the foreign protein.
We can target opsin expression to specific neurons in the brain according to what?
Where their soma are located (e.g., neurons in the amygdala)
Where their axons are located (e.g., neurons that form synapses in the amygdala)
The proteins they express (e.g., neurons that make serotonin or dopamine)
Whether they recently had more action potentials than normal (e.g., active neurons)
Almost all lab-made viral constructs contain a section of DNA that encodes a fluorescent protein (e.g., GFP).
Fluorescent proteins are used to later identify the infected cells.
What is green fluorescent protein
Discovered in Jellyfish
They modified it
Causing it bind calcium and fluoresce much brighter when it does.
This protein is called GCaMP. Since a little calcium influx always occurs during action potentials (even in the cell body), monitoring GCaMP fluorescence is GOOD WAY TO MEASURE NEURAL ACTIVITY (in cells made to express GCaMP protein).
WHat is retrograde labelling
Tracing AFFERENT axons
What brain areas send their axons here? Retrograde labeling is used to label the cells that innervate (project to) a given region.
Various chemicals, such as fluorogold can be used as a retrograde tracer.
Fluorogold molecules are taken up by axon terminals and transported back to the cell body.
What is Anterograde labelling
Tracing EFFERENT axons
Where do the axons from these cells go? Anterograde labeling is used to label where axons from a particular location go to.
Various chemicals, such as PHA-L, can be used as an anterograde tracer.
PHA-L molecules are taken up by cell bodies and transported down to axon terminals.
WHat is Stereotaxic Surgery
Surgical intervention
Uses stereotaxic apparatus
Device that permits a surgeon to put something into a very specific part of the brain
Used to inject things into the brain, such as Drugs and Viruses
Tracer molecules (dyes)
Used to permanently implant things like Cannula and Electrodes
What is a bregma
The junction where pieces of skull fuse together
Often used as a reference point in stereotaxic surgery
Common reasons for stereotaxic surgery
Lesion a brain area
e.g. excitotoxic lesion
Lesion a specific type of cell in a particular brain area
e.g. inject a compound that specifically kills dopamine neurons
Change gene expression
e.g. to remove a gene needed for serotonin synthesis or to deliver DNA that encodes a foreign protein
Typically accomplished with viral-mediated gene delivery.
what is Microdialysis
Used in behaving animals to measure changes in neurotransmitter levels in a given brain region
what is dialysis
refers to the use of a semipermeable membrane to either deliver molecules to or measure the amount of molecules in some solution or brain area.
what is a microdialysis probe
Small metal tube that holds dialysis tubing.
These can be placed in the animal’s head
what is immunochemistry
Histological method that is used to label proteins and peptides in biological tissue
Classify neurons by the protein they possess
Only serotonin neurons express serotonin reuptake proteins.
Only glutamate neurons express vesicular glutamate transporter proteins.
Most common technique for identifying cells that make a specific protein (takes advantage of antibodies - proteins made by the immune system of mammals
Where specific neurotransmitter receptors are located
What neurons in the amygdala express serotonin receptors?
Where are dopamine D3 receptors located in the brain?
fluorescent antibodies
Antibodies, by nature, are designed to selectively bind to a single type of protein.
Researchers have made fluorescent antibodies that selectively bind to all different types of proteins.
When these fluorescent antibodies are washed over a brain slice, the protein of interest will become fluorescently labeled, and under a microscope it is easy to identify which cells contain these proteins.
what is immunochemistry usually used for?
Often used to IDENTIFY PROTEIN EXPRESSION PATTERNS, which in turn tells us WHERE neurotransmitters are RELEASED and WHAT RECEPTORS are there.
To identify cells that make and release classical neurotransmitters
often use antibodies against the enzymes that make these neurotransmitters.
For example, cells must first make serotonin if they plan to release it.
In order to do so, they must express the enzyme tryptophan hydroxylase, which converts the amino acid tryptophan into serotonin.
Therefore, the antibodies that label tryptophan hydroxylase are used to identify serotonin neurons.
