W1: Intro. to Cog. Neuroscience Flashcards
Bear et al. - Neuroscience: Exploring the Brain (60 cards)
1
Q
metaphor / analogy
Neuron + Glial Cell Relationship
A
Imagine a cookie where:
- neurons = chocolate chips
- glia = dough
2
Q
role and function in relation to change + sensations
Neurons
A
- sense changes in environment
- communicate these changes to other neurons
- command the body’s repsonses to these sensations
3
Q
made using what?
Nissl Stain
A
created using a class of basic dyes
4
Q
what does the Nissl stain show?
Nissl Bodies
A
Neuron nuclei + rough ER, stained a violet-blue colour
5
Q
made using what? what does it show?
Golgi Stain
A
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)
6
Q
as opposed to Neuron Doctrine (Cajal)
Reticular Theory
Golgi (the guy) and what he proposed given his findings
A
Golgi created the stain + championed that neurons formed a continuous reticular network
7
Q
as opposed to Reticular Theory (Golgi)
Neuron Doctrine
Cajal (the guy) and what he proposed given Golgi’s findings
A
Cajal argued neurites of different neurons NOT continuous; communicating by contact not continuity
8
Q
structure + composition
Soma
A
watery fluid (cytosol), a salty potassium-rich solution; within the soma are the membrane-enclosed organelles
9
Q
structure and composition, overview of processes (DNA)
Nucleus
A
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
10
Q
locations + summarise processes and outputs
Replication // Transcription // Translation
A
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
11
Q
other name, structure + composition
Rough ER
A
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
12
Q
structure, 2 types, protein synthesis + destinies, why neurons have lots
Ribosomes
A
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
13
Q
function, locations (2)
Smooth ER
A
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)
14
Q
location, structure, function
Golgi Apparatus
A
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)
15
Q
function and general structure
Mitochondrion
A
- Site of cellular respiration (Krebs cycles + ECT)
- Outer membrane + inner membrane folded in on itself (cristae) + matrix (space in-between the two
16
Q
role in neuron + general structure and composition
Neuronal Membrane
A
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)
17
Q
characteristic, 3 components
Cytoskeleton
A
scaffolding that gives neuron its characteristic shape HOWEVER: not static! they are dynamically reguated + in continuous motion
- microtubules
- microfilaments
- neurofilaments
18
Q
diameter, structure, composition, dynamic regulation (MAPs) + e.g.
Cytoskeleton: Microtubules
A
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
19
Q
diameter, structure, composition
Cytoskeleton: Microfilaments
A
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
20
Q
diameter, structure, composition
Cytoskeleton: Neurofilaments
A
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
21
Q
location, regions, branches, protein synthesis
Axon
A
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
22
Q
2 points of comparison
Axon vs. Soma
A
- 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
23
Q
3 components: sides, space, and info. transfer, learning/memory + drugs
Synapse
A
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
24
Q
what (2 words)
Neurotransmitter
A
chemical signal
25
# 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
26
Axoplasmic Transport: Anterograde Transport
kinesin (legs) moving material in direction from soma to terminal
27
Axoplasmic Transport: Retrograde Transport
dynein (legs) moving material in direction terminal to soma
28
# 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
## Footnote
no ribosomes in axon therefore cannot be sustained when separated from their parent cell body
29
# 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
30
# 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
31
# 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
32
# 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*
33
# 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 :))
34
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**
35
# 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
36
# 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
37
# 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
38
# define
Node of Ranvier
the sheath is interrupted periodically, leaving a short length where the axonal membrane is exposed
39
# 3 types, list
Other Non-Neuronal Cells
1. Ependymal Cells
2. Microglia
3. Brain Vasculature
40
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
41
# 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
42
Other Non-Neuronal Cells: Brain Vasculature
arteries, veins, capillaries that deliver essential nutrients and oxygen to neurons via blood
43
# 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
1. **Resting Potential**
2. **Depolarisation / Rising Phase / Overshoot**
3. **Repolarisation / Falling Phase / Overshoot**
4. **Refractory Period**
* **Absolute + Relative Refractory Period**
*pump sets the scene, channels perform*
44
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
45
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)
46
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)
47
AP: Refractory Period
* hyperpolarisation + resting state
* Na+/K+ pump maintains gradient
*Absolute + Relative Refractory Period*
48
# 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**
49
Absolute Refractory Period (ARP)
once an action potential is reached, it is impossible to initiate another for about 1msec -- cannot fire.
50
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
51
# 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+)
52
# 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
53
# 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
54
# 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.
55
# 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*
56
AP Conductance: Orthodrim Conduction
AP conduct (normally) only in one direction -- from soma to axon terminal
57
AP Conductance: Antidromic Conduction
backward propagation, elicited experimentally
58
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
## Footnote
NEED TO CLARIFY HERE!!!! balloon analogy??? and figure out the specific domain
59
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
60
# BOLD signal
Activity Measured by fMRI
* Blood Oxygen Level Dependent signal / measure, oxygen delivery to neurons via blood / brain vasculature
