BIOL 216 Exam 2

How can we study the brain to determine behaviour?

by looking at the mechanisms and neurophysiology

What is methodological reductionism?

understanding a system by analyzing its constituent parts

what are the three components of methodological reductionism?

decomposition: taking something apart to understand what parts it has

internal causes: investigating relationships between parts while simplifying the broader environment

isolating components: studying the features and properties of the parts individually or in limited arrangements

what is the problem with methodological reductionism in neuroscience?

it can be mistaken for explanatory reductionism; interaction of components does not mean mechanism

what are possible explanations for phylogenetic trees having organisms that do not have nervous systems coming after ones that do have them?

nervous system evolved twice, evolutionary reversals, or the phylogeny is wrong

do you need a nervous system to have behaviour?

no, single-celled organisms can show behaviour too

organisms without brains

have less specialized neurons that can detect many things (instead of highly specialized neurons)

two principle cell types in brain

neurons and neuroglia

ways to define neurons

shape (unipolar, bipolar, multipolar), connectivity (sensory neurons, motor neurons, interneurons), neurochemistry (glutamatergic, dopaminergic, cholinergic)

what is the direction of signal flow in neurons?

from dendrite/soma to axon

is the inside of the neuron more positive or more negative than the outside?

negative

what is resting membrane potential of a neuron?

-70 mV

what is the threshold potential of a neuron?

-55 mV

what is the potential when the neuron repolarizes?

+40 mV

what are the cations that contribute to resting potential?

K+, Na+, Ca2+

what are the anions that contribute to resting potential?

Cl-, OA- (organic acids, proteins)

ion channels

Determine the permeability of the membrane to each ion:

Selectivity

• K+ channel

• Cation channel

Gating

• Leak channels (always open)

• Ligand gatedLigand-gated

• Mechanically gated

What are the forces that control the flow of ions?

diffusion and electrical force (and goes until the electrical force is equal to the diffusion force)

ion permeability and membrane potential

the ions that are more permeable have a larger effect on the membrane potential

Nernst Equation

used to calculate equilibrium potential

what do pumps and transporters do?

move ions against their electrochemical gradients to maintain resting potential

what are cotransporters?

membrane proteins that harness the energy of an ion moving in a direction that it wants to across the membrane to move another ion in a direction that it doesn’t want to

cotransporter example

K-Cl symporter, Na-Ca antiporter

where is the synaptic cleft?

between axon terminal and dendrites

example of neurotransmitter and receptor

excitatory: glutamate (neurotransmitter) and AMPA receptor

inhibitory: GABA (neurotransmitter) and GABA receptor

what is a graded potential?

local depolarization (positive charge) of the membrane

what is temporal summation?

when repeated inputs to the synapse give many graded signals, and they get added up (if EPSP). If there are enough they will trigger an action potential.

what is spatial summation?

when multiple dendrites add together spatially to reach threshold

voltage-gated sodium channels

closed when below threshold (-55mV), and open when above. Large increase in membrane potential (to +40 mV) from influx of Na+ ions

voltage-gated potassium channels

at +40 mV, voltage-gated sodium channels close and voltage-gated potassium channels open, bringing a large efflux of K+, and bringing the membrane potential below the resting potential (hyperpolarization)

absolute refractory period

period between opening of voltage-gated potassium channels and hyperpolarization

relative refractory period

period between hyperpolarization and return to resting potential

what is an EPSP?

excitatory post-synaptic potential: increases membrane potential

what is an IPSP?

inhibitory post-synaptic potential: decreases membrane potential

myelination in CNS

oligodendrocytes

myelination in PNS

Schwann cells

space between myelin sheaths

nodes of Ranvier

what does myelination do?

increases the speed of action potentials

voltage-gated calcium channels

rapid influx of calcium allows for vesicles to fuse with the membrane and transmit neurotransmitters. Calcium is in high density in pre-synaptic terminals

what does the calcium cause in a synapse?

it causes a conformational change that allows the vesicle (from readily releasable pool) to fuse with the membrane (slamming it)

what is exocytosis in a synapse?

recovering of vesicle proteins, reforming the vesicle

what is the recycling pool?

the vesicle pool that gets reused by inserting new neurotransmitters to vesicles that had just been used

frequency coding

magnitude of APs stays the same but the frequency of firing changes

Neurotransmitter removal

1. Re-uptake: neurotransmitter re-uptake occurs through membrane proteins, so they do not remain in the synaptic cleft and quickly clear out the cytoplasm. Calcium moves from the synaptic cleft into the axon terminal to close/recycle the vesicle. Drugs can block re-uptake to allow the neurotransmitter to remain in the synaptic cleft for longer (and diffuse more)

2. Degradation: enzymes like acetylcholinesterase will remove neurotransmitters from the synaptic cleft

3. Diffusion: neurotransmitters get diffused to various target receptors on the other side of the synaptic cleft

synaptic plasticity

when an axon of cell A is near enough to excite cell B, and repeatedly fires it, the efficiency of cell A will increase (to fire cell B more too)

what is channelrhodopsin?

a light-gated cation channel, and it stimulates activity when exposed to blue light

what is halorhodopsin?

a light-gated chloride pump that inhibits activity when exposed to yellow light

how to get specificity when studying neurons

• optogenetic excitation (as opposed to electrical stimulation)

• specific promoters (cell type)

• viral injections (spatial)

• drug-inducible expression (temporal)

what is GCaMP?

a calcium indicator used to study brain activity

phase trajectory

plot of how a system evolves in time

attractor

space that phase trajectory tends to evolve toward

dimensionality reduction

When highly correlated dimensions can be reduced to another new dimension, that is a better description of the variance in the data (principal component).

It allows us to describe the activity states of large populations of neurons

what is a manifold?

the shape of the structure when mapping the principal components. It can be coloured by behaviour to show specific parts of phase-based trajectory

it is a lower dimensional surface embedded in a higher dimensional space

what is membrane potential?

the difference in voltage due to the constant presence of ion gradients

small molecule voltage sensitive dyes

change fluorescence in response to changes in membrane potential

fluorescent protein fused to channel protein

fuse fluorescent protein to voltage-sensing domains, fluorescence changes based on membrane potential

fluorescent opsins

light sensitive channel proteins

ex vivo extracellular electrophysiology

electrodes placed near cell bodies of neurons to record the electrical signals. The electrodes can detect changes in the extracellular voltage and provide information about the rate and timing of spikes

ex vivo dual recording electrophysiology

electrodes placed near the cell body and axon of neurons to measure axonal fidelity (propagation of action potential down axon)

Ex vivo intracellular electrophysiology

Electrode inside the cell, allowing you to measure the membrane potential and ionic currents across the membrane. This provides information about a single cell’s electrical properties.

Patch clamp: intracellular activity of single neurons with a high signal-to-noise ratio

Sharp electrode: large leak currents, making voltage-clamp recordings difficult

Voltage clamp

clamps cell membrane at a desired constant voltage and records what currents are being delivered to achieve that voltage (measured in amps). can be used to study ion channel function

current clamp

electrode that records and injects current inside a neuron. You then measure the resulting voltage in response to the injected current. This is used for mimicking electrical signal coming from a synapse or neurotransmitters

Multi-electrode arrays

done while awake

measures:

• spiking activity from multiple neurons in a region

• local field potentials which reflect summed synaptic activity

• Network activity (synchronization and rhythmic patterns)

neuropixels probe

picks up readings of separate neurons

what can GFP be used for?

labelling specific aspects/proteins to focus on and ignoring the rest

what happens to calcium channels as the neuron is depolarized?

they open, causing a huge increase in calcium throughout the cytoplasm

NMDA receptor

when bound to Mg2+, it prevents glutamate from binding. If enough Na+ flows in from an AMPA receptor, NMDA changes conformation (in response to voltage change), removing Mg2+, binding glutamate, and allowing an influx of calcium

methods for large-scale neuronal activity data collection

multi-channel electrodes and calcium imaging

multi-channel electrodes

• measure action potentials from hundreds or thousands of neurons

• allows study of behaviour for large animals

• invasive

• too big for small brain animals

calcium imaging

• non-invasive

• slower time scales (able to detect single APs)

• Depth issues for imaging

Marr’s levels

computation (why), algorithm (what), implementation (how)

why do behavioural states not correspond to synaptic connections?

because the neurons receive input with many neurons, and because the same circuit structure can produce many outcomes

what do neuromodulators (like G-protein receptors and RTKs) do?

they alter the neural signalling properties to produce changes (on a slow time-scale) in circuit dynamics. When a neuromodulator enhances the activity of a synapse, it increases the number of docked synaptic vesicles, to allow for more neurotransmitter release

exafferent sensory input

input from outside world

reafferent sensory input

caused from our own movement

sensory filtration

inhibiting one part of body when doing one behaviour

ex: crickets chirping, desensitize the sound when chirping, when it isn’t chirping it can hear its surroundings

active sensing

create a copy of sensory input and differentiate between input from outside world and from within.

ex: bats; difference between its sound and echo to help with visualization

c. elegans circuit

integrates head position and sensory input to respond to the spatial distribution of the stimuli

sensory and motor signals converge on a single interneuron where they are encoded through separate calcium signalling pathways

“self” representations (corollary discharge) are fundamental to sensory perception