Psych 454 Exam 1

two main types of brain cells

-neurons
-glia

neurons

-signal changes in the environment internal states, action plants, etc.
-100 billion neurons in the brain

glia

-regulate chemical content of extracellular space (astrocytes)
-insulate axons of neurons (oligodendrocytes and Schwann cells)
-about 10 times more glia than neurons in the thalamus, midbrain, and brainstem
-about 1.5 times more glia than neurons in the cerebral cortex

other types of glial cells

-ependymal cells (line fluid filled ventricles and guide cell migration during brain development)
-microglia (remove debris from degenerating neurons and glia)
-vasculature (arteries, capillaries, veins)

parts of a prototypical neuron

-cell membrane
-dendrites
-axon
-cell body (also called "soma")

cell membrane (boundary of the cell)

-lipid bilayer (2 fat layers)
-contains proteins, e.g., receptors, channels

dendrites

-receive input from other neurons
-part of synapses (post synaptic)

synapse

connections between neurons

axon

-provides input to other neurons
-axon hillock: site of action potential generation
-axon terminal: part of synapses (pre synaptic)

cell body (soma)

-gene expression and transcription (nucleus)
-protein synthesis (rough ER, ribosomes)
-protein sorting (smooth ER, golgi apparatus)
-cellular respiration/enery (mitochondria)
-fluid inside cell called cytosol

electric field

-electric field in space around positive source and negative source
-positive ion naturally moves toward negative source of electric field
-negative ion naturally moves towards positive source of electric field

electric potential

-energy needed to move positive ions toward positive source of electric field
-positive ion has more stored energy (electric potential)
-positive ion loses potential energy when it moves towards negative source of electric field

potential difference

-difference in electric potential energy between two sites
-measured in volts (V), i.e. energy per unit charge (joules per coulomb)
-usual range in neurons on the order of millivolts (mV)

current

-movement of charged particles, e.g. Na+, K+

different concentration of ions inside and outside of neuron

-called "concentration gradient"
-ion flows from high to low concentration site

ion channels selectively permeable to particular ions

-channel spans the cell membrane
-channel provides conduit between inside and outside of cell

membrane potential

-electric potential difference between inside and outside of cell
-reflects charge separation across cell membrane

resting membrane potential

-at "rest", inside of cell more negative than outside of cell
-resting membrane potential commonly -65 to -70 mV

when channels open, ions move across membrane

-movement of ions depends on electric potential difference
-positive ions will move towards more negative compartment

depolarization

membrane potential becomes less negative (more positive)

hyperpolarization

membrane potential becomes more negative

when will ions diffuse evenly across membrane

-there are no other driving forces
-diffusion direction down concentration gradient

what is the movement of ions across the membrane determined by

-concentration gradient
-electrical potential difference (membrane potential)

equilibrium potential

electrical potential difference that exactly balances ionic concentration gradient

what is the key determinant of resting membrane potential

-K+
-leak currents through potassium channels at rest
-resting membrane potential close to Ek because it is mostly permeable to potassium at rest)

two classes of ion channels

-voltage gated ion channel
-ligand gated ion channel

voltage-gated ion channel

-channels open at particular membrane potentials
-charged protein subunits of channel change conformation based on membrane potential
-e.g. sodium channel, potassium channel

ligand-gated ion channel

-transmitter/messenger (ligand) opens channel
-binding of ligand changes channel conformation
-e.g. AMPA glutamate receptor (positive ion channel); GABA receptor (chloride channel)

Na+ channels open when membrane depolarizes

-sodium moves into cell
-channel stays open for brief period (1 ms)
-cannot be immediately opened again (1 ms)
-channel inactivated (called "absolute refractory period")

membrane potential threshold

-critical value of membrane potential at which Na+ channels open, generating an action potential
-e.g. around -45 mV

action potential

-rapid change in membrane potential, i.e. brief pulse (1 ms)
-"all or nothing" event, e.g. from -70 mV to +30 mV back to -70 mV
-carries information long distances along axon to connected cells
-after absolute refractory period, can generate more spikes if cell depolarized to threshold

depolarizing phase

-sodium channels open
-inward sodium current

hyperpolarizing phase

-sodium channels close
-(more) potassium channels open
-outward potassium current (resets potential)

concentration gradients reduced during action potential

-to continue generating action potentials, need to reestablish concentration gradients
-i.e. need to move sodium back out of cell, and move potassium back in

sodium potassium pump

-protein that transports Na+ and K+ back across the membrane against their concentration gradient
-consumes much energy (ATP)

action potential propagation

-sodium influx at start of action potential depolarizes membrane just ahead to threshold
-chain reaction, i.e. action potential generates and regenerates along axon
-action potential spreads along membrane with conduction velocity of, e.g. 10 m/s
-action potential can also travel towards cell body, i.e. back propagation (antidromic)

cell membrane separates ions

-more sodium outside cell
-more potassium inside cell

electrical potential difference across cell membrane

resting membrane potential: inside of cell more negative than outside

action potential generated when cell depolarized to threshold

-sodium channels briefly open causing Na+ influx
-membrane potential repolarizes when potassium channels open causing K+ efflux

intracellular recordings

-action potentials from targeted cells
-subthreshold membrane potential fluctuations

extracellular recordings

-action potentials (spikes) from nearby cell(s)
-sort spikes based on e.g. shape, to individual cells
-subthreshold fluctuations summed from nearby cells
-these are called "local field potentials" (LFP)

size and shape of electrode contact or tip is important

-a small exposed metal contact or tip of electrode has a high resistance (harder for currents to flow through)
-smaller the exposed metal contact or tip of electrode, smaller the brain area we sample

electrode impedance is an important property of electrodes

-impedance is a measure of resistance plus electrode capacitance (ability to store charge)
-e.g. fine metal tip with only a few microns exposed metal would have a high impedance (>1 megaohm) and be able to isolate spikes from individual neurons
-fine metal tip electrode needs to be within 10's-of-microns from neurons to record spike
-e.g. typical ECoG surface electrode with a larger exposed metal contact might have a lower impedance (around 0.25 megaohms) and not be able to isolate individual neurons

local field potential (LFP) recordings

-LFP from extracellular depth electrode: reflects e.g. up to 1000ish cells; derived mainly from within 250 microns of electrode tip
-LFP from electrocorticography (ECoG): intracranial recordings from epilepsy patients; performed to localize seizure activity (but also research); electrodes on exposed brain surface (subdural); derived mainly from superficial layers of cerebral cortex

electroencephalography (EEG)

-reflect e.g. 100s of thousands to millions of cells
-summation of synchronized activity of neurons with similar spatial orientation
-predominately derived from pyramidal cells in cortex
-electrodes above scalp (arranged in cap for ease of use)
-i.e. non invasive
-skull smears EEG signal, degrading source localization
-deep brain structures inaccessible to EEG
-poor spatial resolution, but good temporal resolution

functional magnetic resonance imaging (fMRI)

-excite hydrogen atoms with magnetic fields
-measure emitted radio frequency signal
-indirect measure of neural activity
-blood oxygen level dependent (BOLD)
-reflects subthreshold membrane potentials
-i.e. better correlated with LFP than spikes
-spatial resolution, e.g. 2x2x2 mm^3; better than EEG
-poor temporal resolution (e.g. sample every 2 s)

how does the brain code information

-spike rate code, i.e. number of spikes in a given interval: much, much evidence for rate coding across the brain; generally speaking, increasing stimulus intensity, increases the number of spikes (up to a point)
-pooled response code: number of spikes from multiple cells in a given interval; combining activity from many cells reduces "noise" from variability of individual cells

label-line code

-vector formed from joint firing of multiple neurons
-which neurons fire as well as the number of spikes is important here

potentially more information in spike train than just number of spikes?

-spikes do not always reoccur after a fixed time, i.e. there is variability in spike timing
-is it simply "noise" in the system?
-or could it be useful information?

spike timing codes (temporal codes)

-spike pattern code
-spike phase code

spike pattern code

-temporal pattern of spikes in a given interval
-each interval is divided into several smaller time bins
-binary code

spike-phase code

-spike timing relative to phase of oscillations
-network oscillations provide a temporal reference frame or clock
-subthreshold fluctuations

decoding neural activity

-patter classifier: algorithm using multivariate neural activity to predict what image category or class present at time of recording
-2 step process for decoding: training step, test step

training step to decode neural activity

-use subset of data to train classifier
-classifier learns relationship between pattern of neural activity and experimental condition (category or class)
-linear and non linear classifiers

test step to decode neural activity

classifier predicts category in which new data belongs

decoding spike rate

-N neurons and K images: only 2 (out of N) neurons and 2 (out of K) images shown for simplicity; each dot represents spike rate from one image presentation
-training step: red dots correspond to spider image; blue dots correspond to Tower of Pisa image
-test step: new data (gray dot) is assigned to the class of its nearest neighbor (Tower of Pisa predicted)

how well can we identify images based on spike rate

-in inferior temporal cortex
-results based on novel single image presentation

how can we identify images based on fMRI signals

-fMRI data are noisy: generally need to average over many trials; decoding fMRI data from a single image presentation significantly reduces accuracy

what neural signal to measure in neural prostheses

-spikes, but requires invasive technique
-LFP, but requires invasive technique
-fMRI is noninvasive but not portable
-EEG is noninvasive and portable (reduced decoding accuracy with EEG and fMRI)

what is required from a neural prosthesis

-stable long term neural recordings from large numbers of neurons
-efficient (real time) computational data analysis
-brain plasticity to incorporate feedback from effector (e.g. brace

what neural prostheses are being developed

-intracranial implants (recording spikes and/or LFPs)
-EEG based devices

frontal lobe

decision-making, planning, motor control

parietal lobe

touch, spatial transformations

temporal lobe

hearing, higher-level vision

occipital lobe

vision

first order thalamic areas

thalamic areas that receive major input directly form the sensory periphery (e.g. eye, ear, skin) are called these

pathways for sensory information to primary sensory cortex

-peripheral sensory organs (i.e. eyes, ears, skin)
-eye --> first order thalamic areas --> primary visual cortex (V1)
-ear --> first order thalamic areas --> primary auditory cortex (A1)
-skin --> first order thalamic areas --> primary somatosensory cortex (S1)
-all cortex areas present in the cerebral cortex

information is further processed in higher-order cortical areas

-direct pathways between cortical areas
-indirect pathways between cortical areas via higher-order thalamus
-feedforward and feedback routes (for both direct and indirect pathways)

cerebral cortex can be thought of as being hierarchically organized

-cerebral cortex contains primary sensory areas, secondary sensory areas, higher-order areas
-low level (i.e. simple) sensory information represented in primary sensory areas
-higher level (i.e. more complex/abstract) information represented in higher order areas e.g. objects in inferior temporal cortex; or goals in prefrontal cortex

feedforward pathways

-directed from posterior to anterior cortical areas
-feedforward pathways generally carry information about the sensory environment
-higher level information is processed more anteriorly along the pathway

feedback pathways

-directed from anterior to posterior cortical areas
-feedback pathways carry information about, e.g. goals, attention priorities, or predictions
-feedback tends to modulate (increase or decrease) neural activity in more posterior areas e.g., to amplify or filter out information based on behavioral context

direct pathways between cortical areas

carry detailed information about sensory stimuli

what is the role of the indirect pathways between cortical areas via the higher-order thalamus

hypothesis: indirect pathways facilitate processing of only the behaviorally relevant information in the cortex

parallel pathways across the cerebral cortex

-how (or where) pathway across dorsal cortex, enabling sensory guided actions
-what pathway across ventral cortex, enabling object perception

structural differences across the cerebral cortex

-neocortex has 6 layers: but different brain areas show different layering
-cytoarchitectonics: referes to arrangement of neurons in brain
-cytoarchitectonic map: for example, Brodmann map

vertical (radial) organization of neurons int he cortex

-if you move an electrode into the brain, perpendicular to the cortical surface, cells tend to share similar response properties
-e.g. cells may signal the same location and/or stimulus feature
-these cells are interconnected and/or share extrinsic connections

(at least) two scales of vertical organization in cortex

-cortical column (also called macrocolumn)
-cortical minicolumn (also called microcolumn)
-columns and minicolumns repeat across the cortex

cortical column

-extends down through cortical layers
-about 0.4 to 0.5 mm in diameter

cortical minicolumn

-column comprised of minicolumns
-minicolumn about 30 to 50 microns in diameter

cell types in the cerebral cortex (excitatory)

-depolarize (excite) the post synaptic cell
-pyramidal, stellate (excitatory in the cortex, but not everywhere in brain)

cell types in the cerebral cortex (inhibitory)

-hyperpolarize (inhibit) post synaptic cells
-double bouquet, small basket, large basket, chandelier, bi-tufted

canonical microcircuit of the cerebral cortex (feedforward)

-column A = primary visual cortex
-columb B = secondary visual cortex
-first order thalamus to layer 4 to layer 2/3 to layer of next column

canonical microcircuit of the cerebral cortex (feedback)

-column A = primary visual cortex
-column B = secondary visual cortex
-from layer 6 of column B to layer 2/3 of column A

differences in brains across species

-humans have much larger higher order thinking areas of the brain
-capable of much more complicated thinking than mouse or macaque

what type of tissue is the prefrontal cortex predominately

-granular frontal cortex
-granular cortex means (sizable) layer 4 present; agranular/dysgranular means no/little layer 4
-rodents don't have a granular frontal cortex
-granular cortex related to higher order thinking
-all three have the ability to make decisions based on rewards, but mice not capable of higher order thinking

what does the cell level afford in terms of functionality

-think about whether cell is excitatory or inhibitory
-think about size and orientation of the dendritic field
-larger dendritic field can integrate input from more cells over larger area

what does the circuit level afford in terms of functionality

-think about lamination pattern (layering) or other arrangement of cells
-think about whether connections are feedforward or feedback
-think about circuit connections and which are absent
-neurons can only operate on the information they receive

what does the systems level afford in terms of functionality

-think about which brain areas are connected and which are not
-are there reciprocal connections? unidirectional?
-unidirectional connection imposes constraints on processing

canonical microcircuit of the cerebral cortex

-layer 4 receives feedforward input from thalamus or another subcortical area
-layer 2/3 sends feedforward output to another cortical area
-layer 5 sends feedforward output to subcortical areas
-layer 6 sends feedback output to the thalamus or another cortical area
-layer 1 receives feedback input from another cortical area (and thalamus)

basal ganglia areas

-putamen
-caudate nucleus
-subthalamic nucleus
-substantia nigra
-globus pallidus

striatum

putamen and caudate nucleus

cortico-striatal-thalamic loop

-functional territories = limbic, associative, sensory, motor
-from all 4 functional territories, move to cerebral cortex, then striatum, then pallidum/nigra, finally to thalamus
-nearly all of the cerebral cortex projects to the striatum except for the primary visual cortex and primary auditory cortex

basal ganglia contribute to

-action selection
-reinforcement learning
-regulate information processing in the cortex
-increased striatal activity can disinhibit thalamus (via direct pathway)
-i.e. striatum inhibits GP internal segment, which removes inhibition of thalamus

hyperdirect pathway

cortex to subthalamic nucleus

direct pathway

-striatum to GP internal segment
-GP = globus pallidus

indirect pathway

-striatum to GP external segment to subthalamic nucleus to GP internal segment

cortico-cerebellar system

-cerebellum plays a role in more automatic execution during/after skill learning: cerebellum involved in both motor and cognitive functions
-cerebellum receives copies of commands from motor and prefrontal cortex: copies of commands called "efference copies"
-cerebellum may output predicted sensory consequence of movements: cerebellum may predict new state of body based on efference copy?
-prefrontal cortex to pontine nuclei to cerebellum to thalamus to motor cortex

hippocampus functions

-episodic memory
-spatial navigation
-parahippocampal areas to hippocampus to neocortex
-neocortex to thalamus to parahippocampal areas
-parahippocampal areas directly to neocortex

parahippocampal areas

parahippocampal cortex, perirhinal cortex, entorhinal cortex

six degrees of separation

idea that everyone can be connected in <6 steps