W1: Intro. to Cog. Neuroscience Flashcards
Bear et al. - Neuroscience: Exploring the Brain
metaphor / analogy
Neuron + Glial Cell Relationship
Imagine a cookie where:
- neurons = chocolate chips
- glia = dough
role and function in relation to change + sensations
Neurons
- sense changes in environment
- communicate these changes to other neurons
- command the body’s repsonses to these sensations
made using what?
Nissl Stain
created using a class of basic dyes
what does the Nissl stain show?
Nissl Bodies
Neuron nuclei + rough ER, stained a violet-blue colour
made using what? what does it show?
Golgi Stain
soaking brain tissue in silver chromate solution, making a small percentage of neurons become darkly coloured in their ENTIRETY (rather than in clumps, bits of bodies)
as opposed to Neuron Doctrine (Cajal)
Reticular Theory
Golgi (the guy) and what he proposed given his findings
Golgi created the stain + championed that neurons formed a continuous reticular network
as opposed to Reticular Theory (Golgi)
Neuron Doctrine
Cajal (the guy) and what he proposed given Golgi’s findings
Cajal argued neurites of different neurons NOT continuous; communicating by contact not continuity
structure + composition
Soma
watery fluid (cytosol), a salty potassium-rich solution; within the soma are the membrane-enclosed organelles
structure and composition, overview of processes (DNA)
Nucleus
contained within double membrane (nuclear envelope), containing DNA
- (for replication + transcription to create messenger RNA as DNA can never leave the nucleus to then bind with ribosome –> translation, protein synthesis)
- DNA -(Transcription)-> mRNA -(Translation)-> Protein
locations + summarise processes and outputs
Replication // Transcription // Translation
NUCLEUS
Replication
- unwind coils (DNA helicase), breaking H-binds b/w bases
- DNA polymerase (I, III) create new strand using parent strand as template
Transcription
- Initiation: RNA polymerase binds to DNA at promoter region + double helix unwinds
- Elongation: mRNA becomes longer as nucleotides added to the 3’ OH group
- Termination: mRNA synthesis completed
CYTOPLASM
Translation
- Initiation: assembly of translation complex (mRNA + small ribosomal subunit; tRNA + larger ribosomal subunit)
- Elongation: A-site -> P-site -> E-site
- Termination: termination codon reached, release factor binds to A-site, disassembly of translation complex
other name, structure + composition
Rough ER
ID’ed as Nissl bodies
- ER: endoplasmic reticulum (stacks of membrane)
- Rough ER: ER to which ribosomes are attached; abounds in neurons far more than in glia or most other non-neuronal cells
structure, 2 types, protein synthesis + destinies, why neurons have lots
Ribosomes
dense, globular structures in cytoplasm to which mRNA bind
POLYRIBOS.: stacks of free-floating ribos., attached by what looks like a thin string (actually mRNA)
- Proteins synthesised on rough ER: destined to be inserted in membrane of cell organelles
- Proteins synthesised on free Ribos: destined to reside within the cytosol of neuron
it is not surprising that neurons have so much rough ER; special membrane proteins are what give neurons their remarkable info-processing abilities
function, locations (2)
Smooth ER
heterogeneous, performs different functions in different locations
- some is continuous with rough ER+ believed to be a site where the proteins that jut out from the membrane are carefully folded giving them their 3D structure
- other types regulate the internal concentrations of substances such as calcium (particularly prominent in myocytes where it is called the sarcoplasmic reticulum)
location, structure, function
Golgi Apparatus
lying farthest away from the nucelus
- stack of membrane-enclosed disks
- site of post-translational chemical processing of proteins
- sorting of certain proteins destined for delivery to different parts of the neuron e.g. axon + dendrites (neurites)
function and general structure
Mitochondrion
- Site of cellular respiration (Krebs cycles + ECT)
- Outer membrane + inner membrane folded in on itself (cristae) + matrix (space in-between the two
role in neuron + general structure and composition
Neuronal Membrane
barrier enclosing cytoplasm inside the neuron
- Important characteristic of neurons = the protein composition of the membrane varies depending on whether it is in the soma, dendrites, or axon
- “the function of the neuron cannot be understood without understanding the structure and function of the membrane, and its associated proteins”
more generally
- Phospholipid bilayer (hydrophilic/polar phosphate heads, two hydrophobic/non-polar lipid/fatty acid tails)
- protein types: integral, peripheral, transporter, channel (diffusion, along gradient), pump (active transport, against gradient)
characteristic, 3 components
Cytoskeleton
scaffolding that gives neuron its characteristic shape HOWEVER: not static! they are dynamically reguated + in continuous motion
- microtubules
- microfilaments
- neurofilaments
diameter, structure, composition, dynamic regulation (MAPs) + e.g.
Cytoskeleton: Microtubules
roughly 20nm in diameter
Structure + Composition
- relatively larger, run longitudinally down neurites
- straight, thick-walled hollow pipe
- wall of pipe composed of smaller strands braided like rope around hollow corre
- each smaller strand consists of protein TUBULIN (small + globular) + resulting string = polymer
Dynamic Regulation
- polymerisation + depolymerisation of microtubules + of neuronal shape can be regulated by various signals from within the neuron
- e.g. microtubule-associated proteins (MAPs),, changes in an axonal MAP (called tau) have been implicated in the dementia that accompanies Alzheimer’s disease
diameter, structure, composition
Cytoskeleton: Microfilaments
roughly 5nm in diameter
Structure + Composition
- about the same thickness as the cell membrane, found throughout neuron particularly in neurites
- braids of two thin strands that are polymers of the protein ACTIN - one of most abundant proteins in cells of all types (imp. for muscle contraction)
- run longitudinally down the core of neurites, anchored to membrane
diameter, structure, composition
Cytoskeleton: Neurofilaments
roughly 10nm in diameter
Structure + Composition
- exist in all cells of the body as intermediate filaments; only in neurons are they called neurofilaments
- consists of multiple subunits wound together into a rope-like structure
- each strand of the rope consists of individual long proteins, making neurofilaments mechanically very strong
location, regions, branches, protein synthesis
Axon
found only in neurons + highly specialised for the transfer of info. over distances in the nervous system
- Axon Hillock: region marking the beginning of the axon, tapering away from the soma to form the initial segment of the axon proper (beginning of AP)
- Axonal Collaterals: axon often brances off, communicating with different parts of the nervous system
- Recurrent Collaterals: occasionally, axon collateral returns to communicate witht he same celll it originated from
- no ribosomes, no protein synthesis in axon; all proteins in axon must originate from the soma
2 points of comparison
Axon vs. Soma
- No rough ER extends into the axon + there are few, if any free ribosomes in mature axons
- Protein composition of the axon membrane = fundamentally different from that of the soma membrane
3 components: sides, space, and info. transfer, learning/memory + drugs
Synapse
Structure
- Pre-Syn. + Post-Syn.: two sides of the synapes
- Synaptic Cleft: space b/w 2 sides of the synapes
- Synaptic Transmission: transfer of info. at synapse from one neuron to another
electrical-to-chemical-to-electrical transformation of info.
(down axon to terminal to post-sy. membrane)
Application
- learning + memory: modification of synaptic transmission process, involved in memory and learning, and its dysfunction accounts for certain mental disorders
- psychoactive drugs: the synapse is also the site of action for many toxins and most psychoactive drugs
what (2 words)
Neurotransmitter
chemical signal
define + list location, list 2 directional types, 2 speed types
Axoplasmic Transport
Along Microtubules
Movement of material down the axon, process fueled by ATP
Direction
* Anterograde Transport
* Retrograde Transport
Velocity
* Fast Axoplasmic Transport
* Slow Axosplasmic Transport
Axoplasmic Transport: Anterograde Transport
kinesin (legs) moving material in direction from soma to terminal
Axoplasmic Transport: Retrograde Transport
dynein (legs) moving material in direction terminal to soma
define
Degeneration of Axon: Wallerian Degeneration
the degenration of axons that occurs when they are cut - can be detected with certain staining methods and thus a way to trace connections in the brain
no ribosomes in axon therefore cannot be sustained when separated from their parent cell body
greek derivation, classif. method, function, structure, spine, cytoplasm
Dendrites
derived from Greek “tree” – dendrites of a single neuron collectively form a dendrite tree, each branch thus called a dendrite branch
the variety of shapes + sizes of dendritic trees used to classify different groups of neurons
Function & Structure
- antennae of the neuron, covered with thousands of synapses
- Receptors: specialised protein molecules located in the dendritic membrane under synapse (post-synaptic)
-
Dendritic Spines: some neurons covered with these specialised structures, receiving some types of synaptic input
a) believed to isolate various chemical reactions triggered by some types of synaptic activation
b) spine structure = sensitive to type + amount of synaptic activity; unusual changes in spines has been shown to occur in brains of individuals with cognitive impairments - Dendritic Cytoplasm: for the most part resembles that of axon, filled with cytoskeletal elements + mitochondria. One diff = polyribos. observed in dendrites, often right under spines
List Methods (2) and Subtypes (4, 1)
Classification of Neurons
Neuronal Structure
1. number of neurites (axons + dendrites)
2. shape / character of dendrites
3. number of connections
4. axon length
Gene Expression
1. neurotransmitter use
3 types
Classification Based on Neuronal Structure: Number of Neurites
number of neurites (axons + dendrites) that extend from soma
- Unipolar: a single neurite
- Bipolar: two neurites
- Multipolar: three or more neurites
2 types (overlapping)
Classification Based on Neuronal Structure: Dedritic Tree Shape
1) named according to shape or form of trees
2) name according to whether they have spines (SPINY) or not (ASPINOUS)
but these classification schemes can overlap
connection types (3)
Classification Based on Neuronal Structure: Connections
- Primary Sensory Neurons: neurons that have neurites in sensory surfaces of the body
- Motor Neurons: neurons that have axons that form synapses with the muscles + command movements
- Interneurons: form connection only with other neurons (this is most of them :))
Classification Based on Gene Expression
most differences between neurons now understood ultimately via explanations at a genetic level
- role of neurotransmitters: differences in neurotransmitters arises in differences in the expression of the proteins involved in transmitter synthesis, storage, use
- e.g. all motor neurons that command voluntary movements release acetylcholine at their synapses, thus classified as cholinergic
greek derivation, function (3) in relation to neurons
Glia(l Cells)
greek for glue, suspending neurons in appropriate locations
contribute to brain functioning by
a. insulating
b. supporting
c. nourishing
neighbouring neurons
how abundant, function/purpose general + specific (2)
Glial Cell: Astrocyte
most numerous glia in the brain, filling most of space b/w neurons thus most likely influencing whether a neurite can grow / retract
- regulate chemical content of the extracellular space (e.g. K+ concentration)
- have special proteins in their membranes that actively remove many neurotransmitters from the synaptic cleft
2 types, functions
Glial Cell: Myelinating Glia
the functions of the 2 are much clearer than that of astrocytes
- Oligodendroglial: ONLY CNS
- Schwann Cells: ONLY PNS
provide layers of membrane that insulate axons; because the axon fits inside the spiral wrapping like a sword in its scabbard, myelin sheath describes its entire covering
- Myelin is actually white thus mostly myelinated axons constituting the white matter thus there are no cell bodies
- cell bodies mostly making up the grey matter
define
Node of Ranvier
the sheath is interrupted periodically, leaving a short length where the axonal membrane is exposed
3 types, list
Other Non-Neuronal Cells
- Ependymal Cells
- Microglia
- Brain Vasculature
Other Non-Neuronal Cells: Ependymal Cells
live, fluid-filled ventricles within the brain + play a role in directing cell migration during brain development + involved in the production of CSF
general nature + function, microglial invasion significance
Other Non-Neuronal Cells: Microglia
class of cells functioning as phagocytes removing debris left by dead or degenerating neurons + glia
- appear to be involved in remodelling synaptic connections by gobbling them up
- they can migrate form the blood into the brain and disruption of this microglial invasion can interfere with brain function + behaviour
Other Non-Neuronal Cells: Brain Vasculature
arteries, veins, capillaries that deliver essential nutrients and oxygen to neurons via blood
other names + general definition, list 4 periods
Action Potential
spike, nerve impulse, discharge
sudden, fast, transitory, and propagating change of the resting membrane potential
the frequency + pattern of action potentials constitute the code used by neurons to transfer info. from one location to another
- Resting Potential
- Depolarisation / Rising Phase / Overshoot
- Repolarisation / Falling Phase / Overshoot
-
Refractory Period
* Absolute + Relative Refractory Period
pump sets the scene, channels perform
AP: Resting Potential
- stable electric charge across a neuron’s membrane when it’s not actively sending signals
- typically ranging from -75mV to -55mV
- Maintained by mixture of non-voltage-dependent conductances
- primarily K-selective channels like KCNK channel
- threshold at ca. -55mV
AP: Depolarisation / Rising Phase / Overshoot
- membrane voltage rapidly rises to approx. 40mV
- causes Na+ voltage-gated channels to open in the membrane
- Na+ diffuse into cell (Na+ influx, more positive inside relative to outside)
AP: Repolarisation / Falling Phase / Overshoot
- potential diference reaches 40mV
- Na+ voltage-gated channels close
- K+ channels open, large efflux diffisuion of K+ out of cell
- falling membrane potential (K+ efflux)
AP: Refractory Period
- hyperpolarisation + resting state
- Na+/K+ pump maintains gradient
Absolute + Relative Refractory Period
y/n, grounding, further elaboration (caveats)
Is it possible to generate multiple action potentials?
Action potential is like a fuse – except it regenerates,, of course, that regeneration also takes some time :)
yes, if we pass continuous depolarising current into a neuron via a microelectrode we generate many action potentials in succession
(still the rate of action potential generation depends on the mangitude of the continuous depolarising current)
HOWEVER: Note the ARP and RRP
Absolute Refractory Period (ARP)
once an action potential is reached, it is impossible to initiate another for about 1msec – cannot fire.
Relative Refractory Period (RRP)
occurs after ARP, possible to produce another action potential, but requires much greater stimulus / elevated amount of current to reach the threshold
simple, one-to-one (for sake of understanding)
Firing Frequency - Stimulus Relationship
Firing frequency directly related to the magnitude of the stimulus and thus how many neurotransmitters are released (ofc further mediated by e.g. presence of Ca+)
old, new
Method: How is the generation of multiple action potentials made possible?
OLD: Microelectrode
injecting electrical current to artificially control neural firing rates
NEW: Optogenetics
introduces into neurons foreign genes that express membrane ion channels that open in response to light
structure/composition, pattern of beh., role in AP generation, AP + NA
Voltage-Gated Sodium Channels
Structure + Composition
- the protein forms a pore in the membrane that is highly selective to Na+ & the pore is opened and closed by changes in membrane voltage
- 1 α subunit that forms the pore (accompanied by one or more auxiliary β subunits) > 4 homologous domains (I–IV) > 6 transmembrane α-helices (S1-S6).
- S4 segment within each domain = voltage sensor, responding to changes in membrane potential.
- S5 and S6 segments + a re-entrant loop between them, form the pore and selectivity filter, ensure high selectivity for Na⁺ ions.
- gate
Pattern of Behaviour
- they open with little delay
- they stay open for ca. 1msec then close (inactivate)
- they cannot be opened again by depolarisation until the membrane potential returns to negative value near threshold
Role in Action Potential Generation
- a single channel does not make an action potential
- the membrane of an axon may contain thousands of Na channels per square micrometer (µm^2) and the concerted action of all these channels i required to generate what we measure as an action potential
Properties of APs that can be Explained by Properties of NA channels (voltage-gated)
- the fact that single channels do not open untila critical level of membrane dep. is reached explains AP theshold; the rapid opening of the channels in response to dep. explains why the rising phase of the AP occurs so quickly
- the short time the channels stay open before inactivating partly explains why the action potential is so brief
- inactivation of the channels can account for the ARP: another AP cannot be generated until the channels are activated
structure/composition, pattern of beh., role in AP generation, AP + NA
Voltage-Gated Potassium Channels
leaky K+ channel
Structure and Composition
- tetrameric structures composed of 4 α subunits > 6 transmembrane segments (S1–S6).
- S5 and S6 segments, along with a pore loop (P-loop), form the ion-conducting pore highly selective for K⁺ ions.
- S4 segment acts as the voltage sensor, containing positively charged residues, detects changes in membrane potential, leading to conformational changes that open or close the channel gate.
Pattern of Behavior
- do not open immediately upon dep. (1msec delay)
- thus considered a delayed rectifier as it serves to rectify / reset the membrane potential
- Once opened, these channels often remain open longer than voltage-gated Na⁺ channels and do not inactivate as quickly. Some K⁺ channels exhibit inactivation, but this process varies among different types.
- After closing, voltage-gated K⁺ channels can be reopened by subsequent depolarizations without the need for the membrane potential to return to a specific negative value, unlike voltage-gated Na⁺ channels that require repolarization to near-threshold levels before they can reopen.
Role in Action Potential Generation
- The membrane of an axon contains a high density of K⁺ channels, and their coordinated action is essential for restoring the resting membrane potential after depolarization.
Properties of Action Potentials Explained by Properties of Voltage-Gated K⁺ Channels
- The delayed opening of K⁺ channels after dep. contributes to the rep. phase of the action potential, helping to terminate the peak of the action potential.
- The prolonged open state of K⁺ channels facilitates the efflux of K⁺ ions, driving the membrane potential back toward its resting negative value, which explains the falling phase of the action potential.
metaphor!, list 2 types of conduction, approx. velocity + duration of AP
Action Potential Conductance
AP intiated at one end of the axon propagates only in one direction; does not turn back on itself and without decrement – like a fuse ;)
this is because the membrane behind it is refractory, due to inactivation of sodium channels
- Orthodrim Conduction
- Antidromic Conduction
AP conduction velocities vary, but 10m/sec is a typical rate – start to finish AP last ca. 2msec
AP Conductance: Orthodrim Conduction
AP conduct (normally) only in one direction – from soma to axon terminal
AP Conductance: Antidromic Conduction
backward propagation, elicited experimentally
AP + Axonal Size and No. of Voltage-Gated Channels
axonal size + no. of voltage-gated channels also affect axonal excitability
- smaller axons require greater dep. to reach AP threshold and are more sensitive to being blocked by local anaesthetics
- therefore binding to the alpha-helices of the Na voltage-gated channel (of a certain domain) inside the pore, interfering within the flow of Na+ that nromally results from the dep of the channel
NEED TO CLARIFY HERE!!!! balloon analogy??? and figure out the specific domain
Activity Measured by EEG
- EEG will not pick up on an AP of a single neuron
- when there are more, then the EEG can pick up on this
BOLD signal
Activity Measured by fMRI
- Blood Oxygen Level Dependent signal / measure, oxygen delivery to neurons via blood / brain vasculature
