Chapter 2: Flashcards
Peripheral Nervous System
Grey Matter is in the middle: Cell bodies, the somas
Dorsal: Sensory
White matter: Neuron axons, the tracts.
Ventral root: Motor
31 pairs of spinal nerves
Spinal Reflexes
Spinal cord has two parallel pathways
Sensory Nerves: Dorsal Root
Motor Nerves: Ventral Root
Bell-Megendie Law of Neural Specialization
Sensory / Motor information segregated at level of PNS and CNS
Afferent:
projections to CNS, brain region, or neuron
Efferent
projections from CNS, brain region, or neuron
Autonomic Nervous System
Two divisions:
Sympathetic
Parasympathetic
Regulate 4 critical bodily states related to survival—i.e., the 4 Fs: Fighting Fleeing Feeding sex
FIGHT-or-FLIGHT
Sympathetic Autonomic Nervous System
REST-and-DIGEST
Parasympathetic Autonomic Nervous System
Neuron facts
Human brain ~ 100 billion neurons
More than 100 types of neurons
5,000 to 80,000 synapses per neuron
1,500 TRILLION synapses/human brain
Dendrites
Dendritic tree
Collection of dendrites from single neuron
Dendritic spines
Contact point between axon and dendrite
Low dendritic spine number is correlated with mental retardation
Elevated spine density correlated with autism
TYPICALLY synapses form at the spines
Spine Density in the Hippocampus Impacted by External & Internal Factors
Enriched environment leads to denser spines
High expression of dendrites during estrous.
Rodents learn better when they are ovulating.
More spines: more synaptic synapses, better for learning
The Soma
Cytoplasm: cytosol & organelles
Nucleus: contained in nuclear envelope
Gene expression
~23000 human genes
Transcription: mRNA assembly
Translation: Assembly of proteins from 20 amino acids
Some animals and plants have more genes than we do.
Cell Membrane segregates ions inside cell from ions in extracellular fluid
Channels provide a path for ions to cross back and forth across membrane
Ionic movement is influenced by:
Diffusion
An ion’s concentration gradient across the membrane
Electricity
The separation of ionic charge across the membrane
Seeking Equilibrium
Sodium
Na+
Higher concentration OUTSIDE of cell
Both Diffusion and Electrical Force attract Sodium INTO the cell
Depolarize
Potassium
K+
Higher Concentration on the INSIDE.
Diffusion pushes Potassium out; electrical force sucks Potassium in.
Hyperpolarize
Calcium
Ca2+
Higher concentration OUTSIDE of cell
Chloride
Cl-
Higher concentration OUTSIDE of cell
Diffusion pushes chlorine in; electrical force pushes chlorine out
In the case of chloride,
Diffusion is much stronger than the electrical force.
So Chlorine goes INTO the cell
Hyperpolarized
The inside of the cell is _____ charged.
The inside of the cell is negatively charged.
depolarization
As the sodium rushes back into the cell the positive sodium ions raise the charge inside of the cell from negative to positive.
Once the interior of the cell becomes positively charged, depolarization of the cell is complete.
MORE POSTIVE
Hyperpolarization
Hyperpolarization is a change in a cell’s membrane potential that makes it more negative.
Inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold.
Resting membrane potential
The difference in charge between the inside and outside of the membrane of a neuron at rest
AT REST, THE INSIDE OF THE NEURON IS AT______
AT REST, THE INSIDE OF THE NEURON IS AT -70 MV
The Axon
Axon hillock (beginning), Axon proper (middle) and Axon terminal (end) Relays action potentials when membrane potential depolarizes past threshold
All-or-none
Action potentials
All-or-nothing.
A binary event.
Rising phase:
Na+ enters neuron
Depolarization
Overshoot:
Neuron positive inside. Up to about 40 MV
Falling phase:
K+ exits neuron
Repolarization
Falling phase is due to opening of potassium channels that are opened but delayed just for a moment (enough to reach peak) and then potassium flows out.
The potassium channels are a bit delayed in closing, which gives us the after hyperpolarization period where another spike is impossible unless an incredibly strong stimulus is given.
AHP: After hyperpolarization. Needs a much stronger stimulus to activate it. Essentially a limit on temporal excitability.
STEP 1 of Action Potential
Rising phase
Na+ enters neuron
Depolarization
STEP 2 of Action Potential
Overshoot
Neuron becomes so depolarized that it’s positive inside
STEP 3 of Action Potential
Falling phase
K+ exits neuron, making cell more negative, hyperpolarizing the cell
Repolarization
Potential is just another word for ______
Potential is just another word for voltage
The membrane at the _____ depolarizes, then we reach _____, then we initiate an ____
The membrane at the axon hillock depolarizes, then we reach threshold, then we initiate an action potential
Action Potentials
Communication
Convey information over distance in nervous system
Neural information code:
Pattern (temporal code)
Frequency (rate code)
Saltatory conduction
From the Latin “saltare,” to hop or leap.
The propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials.
Synapse
point of contact between presynaptic axon terminal and another (postsynaptic) neuron
Information is passed directionally from presynaptic to postsynaptic cell
1897: Charles Sherrington coined term “Synapse”
Soups vs. Sparks Debate
Physical nature of synaptic transmission
Chemical vs. Electrical transmission
It is a chemical signal that is released at the presynaptic terminal.
At gap junctions, the signals are electrical and bidirectional.
These form a minority of the communication methods in the brain.
Chemical Synapses
Presynaptic terminals release
chemical signals.
Neurotransmitters regulate information transfer
Neurotransmitter Cycle
- Synthesis/Packaging of Neurotransmitter into Vesicles
- Exocytosis: fuse with membrane and spill contents
- Receptor Binding: neurobind to postsynaptic receptors.
What happens after the Neurotransmitter release? There are several possibilities:
Inactivation
Reuptake
Diffusion
Neurotransmitters:
Amino acids
GABA (inhibitory)
glutamate (excitatory)
Neurotransmitter Types
Small molecules, often called neuromodulators:
serotonin, norepinephrine, epinephrine, dopamine, acetylcholine
Amino acids:
GABA (inhibitory), glutamate (excitatory)
Neuropeptides (small protein):
secretin, oxytocin
*Soluble gases:
nitric oxide, carbon monoxide
*Typically, these Gases are Retrograde messengers: typically released from the postsynaptic terminal to the presynaptic.
Neurotransmitters:
Neuropeptides
small proteins
secretin, oxytocin
Neurotransmitters:
Soluble gases
nitric oxide, carbon monoxide
Typically, these Gases are Retrograde messengers:
typically released from the postsynaptic terminal to the presynaptic.
Too much excitement:
seizures
Too little excitement:
lethargy, drowsiness, coma
Synaptic Transmission
Neurotransmitter binds to postsynaptic receptor
Ionotropic receptor: opens and ions flow in or out.
Ionotropic receptors typically act very rapidly.
Chloride coming in is inhibitory; it hyperpolarizes.
Ionotropic receptor:
opens and ions flow in or out.
Ionotropic receptors typically act very rapidly.
Graded Potentials
EPSP: Depolarization
IPSP: Hyperpolarization
Influx of sodium –> Depolarization
Graded Potentials,
Synaptic Integration
Combining a number of individual signals into one overall signal
Two ways:
spatial summation
temporal summation
Spatial Summation: are they physically close together. Near in Distance
Temporal Summation: are the close together in time.
Summation of EPSP makes action potential is MORE likely
Summation of IPSPs makes action potential is LESS likely
Graded: There’s an infinite range. Analog
Action potentials are not Graded
If we want to inhibit neuron from firing, we want to put IPSPs close to the axon hillock
Neuromodulators
Serotonin
Epinephrine
Norepinephrine
Dopamine
S-E-N-D
NT that diffuses broadly; is not reabsorbed by the presynaptic neuron or broken down into a metabolite
Acts on G-protein coupled receptors, slow-acting receptors that trigger downstream changes in neuronal function
Alters how neurons exchange messages – i.e., change in gain or signal-to-noise.
Make it easier to decipher the signal from the noise
Neuromodulators usually work through Metabotropic Receptors or GPCR
Metabotropic Receptors are slow
signal-to-noise: any biological process has background noise.
Autism
Alzheimer’s
Parkinson’s
Synaptic Plasticity:
Synaptic Plasticity: different from synaptic transmission
Learning Effects brain function how??
Santiago Ramon y Cajal: The Neuron Doctrine
Cajal: Learning involves changes in synapses, strengthening or weakening information transfer
Donald Hebb: Hebbian Plasticity
Neurons that fire together, wire together!!!!
Cell Assembly:
group of interconnected neurons representing learned phenomenon (perception, memory, response, etc.)
Forms when cells are contiguously active, enhancing connections [i.e., synapses] between cells
Built on Cajal’s Ideas
contiguously = close together in space or time
When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.
Cell Assembly:
group of interconnected neurons representing learned phenomenon (perception, memory, response, etc.)
Long-term Potentiation
cellular mechanism for strengthening synaptic connections between neurons
Most commonly studied in hippocampal slices
First demonstration:
Lomo & Andersen (1968)
Repetitive high frequency electrical stimulation caused increase in the postsynaptic EPSP
Enhancement of the EPSP after the high frequency stimulation
Experience-dependent change
LTP = Synaptic Modification
In neuroscience, an excitatory postsynaptic potential (EPSP) is a postsynaptic potential that makes the neuron more likely to fire an action potential.
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential.
Generation of Post Synaptic Potential
[Excitatory] EPSP: Glutamate
High frequency stimulation increases postsynaptic EPSP
Glutamate receptors
AMPA receptors: allows sodium influx when channel opens (depolarizing)
NMDA receptors
AMPA receptors
Normal ionotropic
allows sodium influx when channel opens (depolarizing)
NMDA receptors
Dual-gated, ligand-gated and voltage gated
Dual-Gated:
Requires GLUTAMATE binding to postsynaptic receptor.
Requires postsynaptic depolarization —> removes Mg++ blockade
Coincidence Detection:
NMDA receptor activation signals coincident presynaptic activity (glutamate release) and postsynaptic activity (depolarization)
Calcium’s concentration gradients
Calcium is a second messenger
Action potentials briefly depolarize the entire neuron; including the soma and dendrites. So the spike starts at the axon hillock, but does just effect that local area
Postsynaptic glutamate
LTP expression responsible for enhanced EPSP
Increased presynaptic glutamate release
Insertion of new AMPA Receptors into postsynaptic cleft
Postsynaptic AMPA Receptors modified (phosphorylated), allowing the receptor channel to stay open longer
All 3 modifications result in more sodium influx (depolarization)
LTM (Long-Term Modifications): Formation of new synapses
At a synapse: Probability of release for most neurons .
Spine heads actually get bigger (to accommodate?) LTP
These 3 modifications don’t last forever. But they develop Anatomical Morphological changes…
Homosynaptic LTP
occurs at one synapse
Weak input: no LTP
Strong Input: LTP (see the increase in the response)
Weak and strong input must be activated near in time, in which case the weak input benefits from postsynaptic depolarization (provided by strong input) and is strengthened accordingly
If the weak and strong are done together, the EPSP is stronger afterward with just the weak
Long-term Depression
Generally occurs when presynaptic activity or postsynaptic activity occurs alone (i.e., it is not coincident)
FEAR CONDITIONING in MICE:
Weak Stimulus: Conditioned Stimulus (Tone)
Strong Stimulus: Unconditioned Stimulus (Shock)
Associative LTP: any synapse active at time of postsynaptic depolarization undergoes synaptic modification
Desynchronization weakens the synapse.
We can Remove AMPA receptors or de-phosporylate them to weaken synapse
Synaptic Plasticity:
LTP and LTD
LTP and LTD have now been demonstrated to occur in multiple brain areas, including the hippocampus, prefrontal cortex, amygdala, and cerebellum
Considered universal mechanisms for altering the efficiency of connections between neurons
LTP & Learning
Evidence good but not conclusive:
- LTP and LTM are both triggered rapidly and can last a very long time
- Learning produces synaptic physiology changes similar to those caused by LTP
Blocking LTP can prevent learning
Transgenic rat (Doogie) with enhanced LTP shows better learning
LTM : here means long-term memory
Strong Calcium pulse: changes in ampa receptors, triggers LTP
Weak Calcium pulse: sporadic, dribbling leads to LTD
long-term potentiation (LTP)
a persistent strengthening of synapses based on recent patterns of activity.
These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression (LTD), which produces a long-lasting decrease in synaptic strength.
It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.
LTP was discovered in the rabbit hippocampus by Terje Lømo and has remained a popular subject of research since.
Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still others try to develop methods, pharmacologic or otherwise, of enhancing LTP to improve learning and memory. LTP is also a subject of clinical research, for example, in the areas of Alzheimer’s disease and addiction medicine.
Each hemisphere divided into 4 lobes
Frontal: executive function
Parietal: sensory integration
Temporal: auditory, taste, smell, memory
Occipital: visual
Topographic map
Body information is systematically organized in sensory and motor cortices
Homunculus
Many sub-cortical structures engaged during L&M
Thalamus
Basal Ganglia
Amygdala
Hippocampus
Structural Imaging
CT: computerized tomography
MRI: magnetic resonance imaging
Functional Imaging
PET: positron emission tomography
fMRI: functional MRI
Basic Principles:
Detect changes in regional metabolism and blood flow within the brain.
Active neurons demand more glucose and oxygen, more blood flows to active regions
Computerized Tomography (CT)
Structural Imaging
Uses multiple x-rays to construct a 3D image
X-rays penetrate body and are absorbed by various “radiopaque” tissues
Digital reconstruction within plane of slice
CT is just fancy a x-ray
Forms 3D image of brain by combining X-rays of cross sections of brain; images structure and damage
Magnetic Resonance Imaging (MRI)
Structural Imaging
Uses a magnetic field and radio waves to produce high-resolution structural images of the brain
Particularly hydrogen atoms are lined up
Measures variations in hydrogen concentrations in brain tissue; images structure and damage
Positron Emission Tomography (PET)
Functional Imaging
Injection of a radioactive substance (e.g., 2-deoxyglucose) into the bloodstream, which is taken up by parts of the brain according to how active they are
Baseline measure subtracted from activity during task
Image produced by emissions from injected substances that have been made radioactive; tracks changing activity, detects receptors, etc.
Functional Magnetic Resonance Imaging (fMRI)
Functional Imaging
Changes in blood flow and blood oxygenation in the brain (i.e., hemodynamics) are closely linked to neural activity
Ratio of oxyhemoglobin to deoxyhemoglobin determines areas of brain activation
Detects increases in oxygen levels during neural activity; tracks changing activity
Brain Stimulation
In vivo Stimulation
Transcranial Magnetic Stimulation (TMS)
Brain Stimulation
Pass small current to activate particular brain regions
Clarify role of particular substrates prior to surgery
Transcranial Magnetic Stimulation (TMS)
Applies strong and quickly changing magnetic fields to surface of skull that can interrupt or induce brain activity
Neurophysiology
Electrical activity of neurons:
Electroencephalography (EEG)
Neuronal Recording
Electroencephalography (EEG)
Scalp electrodes provide information about the activity of large populations of neurons
Used to study sleep and diagnose seizures
Described in amplitude and frequency
Aroused vs. Deep Sleep: opposite trends
Evoked Potentials /
Event Related Potential (ERP)
Series of EEG responses to environmental stimuli
Useful in studies of perception, cognitive processes
Neurophysiological Recordings
In vitro Recording
Brain slice removed from dead animal.
Individual neurons can be studied for several hours
Stimulating electrode causes Action Potentials in presynaptic neurons
Recording electrode measure EPSP/IPSP in postsynaptic neurons
LTP Example
Neurophysiological Recordings
In vivo Recording
Record multiple units (neurons) from awake animal.
Unit responding correlated to external stimuli / events
Each electrode can pick up signal from 1-4 neurons
Using mutliple electrodes allows you to locate and quantify the neurons that are being picked up
Neuropharmacology
Drug Infusions
Microdialysis
Understanding how drugs affect neuronal function
Receptor antagonists:
Inhibitors of neurotransmitter receptors
Reduce synthesis
Prevent storage
Block release
Activate presynaptic
autoreceptors
Block postsynaptic receptor
Receptor agonists
Mimic actions of naturally occurring neurotransmitters
Increase synthesis Promote release Block reuptake or degradation Block presynaptic autoreceptors Activate postsynaptic receptor
Methamphetamine is a _____ agonist
Methamphetamine is a dopamine agonist
Drug Infusions
In animals, drug infusion can be localized through use of guide cannula
Drugs can be infused into specific brain regions, activating or inhibiting neuronal activity
Microdialysis
Procedure for analyzing chemicals (e.g. drugs, neurotransmitters) present in the extracellular fluid
Small piece of tubing made of semipermeable membrane implanted in the brain, allowing CSF from subject to flow into probe for collection and analysis
Immunocytochemistry
Uses antibodies attached to a stain or dye to identify the presence of particular proteins, including: Receptors Neurotransmitters Hormones Enzymes
In immunocytochemistry, an antibody attaches to antigen in fixed, mounted, brain tissue
Antibody Binding
In immunocytochemistry, an antibody attaches to antigen in fixed, mounted, brain tissue
- Protein injected into animal so that it makes antibodies
- Blood containing antibodies to the protein formed are removed
- Antibody applied to tissue slices and tagged to make visible
- Only neurons containing antigen are labeled
Biochemistry
Quantifies the amount of gene, mRNA, or protein in a sample
PCR: Detects specific genes in tissue sample
Western Blots: Detects specific proteins in tissue sample
Genetic Methods
Twin studies
Genetically modified animals
Optogenetics
Twin Studies
Compare variable of interest between identical (monozygotic) and fraternal (dizygotic) twins
Contribution of heredity is stated as Concordance Rate
The higher the Concordance rate, the higher role that genes are assumed to play.
If its low, than environment had more influence, presumably
Genetically Modified Animals:
Knock-out or knock-in genes
Protein production blocked or added
Knock-out: removing a gene
Can also inactivate genes, even inactivate genes in a specific location or at a specific time (like waiting until they are adult) by using certain drugs
Optogenetics
Been around for about 10 years
Offers a high degree of specificity on which neurons are activated
The firing characteristics of Hippocampal neurons?:
immunocytochemistry
The role of a particular gene or protein?
Knockout
Localization of function
Phrenology
Franz Josef Gall: 1758-1828
Johann Casper Spurzheim: 1776-1832
Thought that he brain grows and changes the shape of the skull
Making inferences about bumps on the skull
The Localtity of function is an important important, but the whole phrenology thing is completely false
Gage’s Personality
Before the Accident:
- responsible
- intelligent
- socially well-adapted
After the Accident:
- intelligence, speech, learning, movement remained intact
- no sense of responsibility
- no respect for social conventions
- profane
- irreverent
Paul Broca
1824-1880
Post-mortem examination related to language production impairment
“Tan, tan, tan…..” Intact comprehension
Carl Wernicke
1848-1905
Post-mortem examination related to language comprehension impairment
Brains composed of multiple systems specialized in collecting, processing, and storing particular kinds of information
One brain area may a play role in many functions; one function may rely on many brain areas
Brain Lesions in animals allow a precision not possible in human studies
What about learning and memory function?
Karl Lashley: 1890-1958
Maze Learning
Simple task that may allow specific brain regions to be associated with successful learning and memory
Karl Lashley
Lashley intended to find evidence for:
Engram: Neurophysiological locus (physical location) of a specific memory
Instead he settled on:
Theory of Equipotentiality: Memories not stored in one area; brain operates as a whole to store memories
Maze Learning
Simple task that may allow specific brain regions to be associated with successful learning & memory
The animals were compensating with their still funtioning abilities.
As Lashley (1950) put it himself: “This series of experiments has yielded a good bit of information about what and where the memory trace is not. It has discovered nothing directly of the real nature of the memory trace. I sometimes feel, in reviewing the evidence of the localization of the memory trace, that the necessary conclusion is that learning is just not possible. It is difficult to conceive of a mechanism that can satisfy the conditions set for it. Nevertheless, in spite of such evidence against it, learning sometimes does occur.”
Most people don’t agree on theory of E. and the Engram is still up in the air
Is there an Engram??
Eyeblink Classical Conditioning in rabbits. rabbits can’t condition without a certain area
