Biopsychology Exam 3 (Final Exam)

how are memories stored in the brain?

synaptic changes (long-term potentiation - LTP)

where are memories stored in the brain?

it varies across and within domains (pavlovian & operant conditioning, declarative / representational memory)

learning

a modification in the behavior of an organism as a result of experience

memory

the retention of information / modifications over time

neural plasticity

the neural change underlying the behavioral change (aka the 'memory trace')

neural changes

changes in synaptic strength or connectivity

to alter protein synthesis, what do long-term memories use in addition to neural changes?

epigenetic changes

changes in synaptic strength

result of LEARNING, in order to release neurotransmitter more readily

- change can involve synaptic transmitters or interneuron modulation

changes in synaptic connectivity

neuron may 1. form new synapses (add conductivity) or 2. rearrange synaptic input (change 'who is talking to who')

how does synaptic strength change?

non-associative learning and associative learning

non-associative learning

one stimulus, habituation

habituation

repeated stimulus induces diminished response (initially pre-synaptic alterations)

associative learning

two stimuli; long-term potentiation (LTP)
- both PRE and POST-synaptic alterations
- pavlovian conditioning

habituation studied in Aplysia (a 20k neuron snail)

- siphon = part of snail that pulls in water to the gills (for organism to breathe)
- touching the siphon makes both the siphon and gill contract (both are sensitive tissue)
- contraction of the siphon and gill are controlled by two different motor systems
- repeatedly touching siphon causes diminished response

measured habituation in Aplysia

contraction response of touching siphon becomes increasingly weaker
- Ca2+ channel inactivates -> less Ca2+ coming into the cell -> reduction in release of nT of presynaptic neuron

how do we know the reduced contraction of the Aplysia's siphon is not due to muscle fatigue? what about sensory adaptation?

- NOT muscle fatigue: measuring the motor neuron of the siphon shows the habituated response
- NOT sensory adaptation: electrically stimulating the sensory neuron, showing that response is not weakened

alternative mechanism of non-associative learning

sensitization

sensitization

an increase in behavioral response after exposure to a stimulus

sensitization in the Aplysia

shocking its tail causes the organism to change its behavioral state & be more responsive to everything / amplify its response, even to gill withdrawal (which is unrelated to shock)

2 habituation mechanisms

short-term habituation and long-term habituation

short-term habituation

decreased neurotransmitter release from sensory to motor neuron
- inactivation of Ca2+ channels -> decrease in nT release
- does NOT alter gene expression

long-term habituation

post-synaptic changes involved; post-synaptic receptor down-regulation (LTD)

- protein synthesis dependent

- requires changes in gene expression

- days to weeks, eliminating long-term memory

Pavlovian conditioning

type of associative learning; involves pairing a biological stimulus with a neutral stimulus to elicit a response

original Pavlov experiment

- Food = unconditioned stimulus (UCS)
- Salivation = unconditioned response (UCR)
- Bell = conditioned stimulus (CS)
- Salivation = conditioned response (CR)

stimulus-stimulus association

the organism learns to associate the CS with the UCS, which is why the response is produced

example of S-S learning

- tone + sucrose -> response
- devalue sucrose
- tone alone -> diminished response

stimulus-response association

CS directly causes the CR to occur

types of S-R learning

primary association and secondary conditioning

primary association

- CS -> US -> UR
- So, CS -> CR

secondary conditioning

- CS2 -> CS1 -> CR1
- So, CS2 -> CR1
- CS2 associated with CS1 associated with response

sign tracking

a type of elicited behavior in which an organism approaches a stimulus that signals the presentation of an appetitive event

example of sign tracking in pigeons

- key light predicts food

- pigeons peck the key light (even though it does not deliver food itself)

- pigeons cannot NOT peck the key light

- in addition, beak shape will change depending on what UCS you choose:

- if trained with food, will peck with food-shape beak

- if trained with water, will peck with water-shape beak

psychological explanation of associative learning

Hebbian learning and temporal contiguity

Hebbian learning

if neuron A activity coincides with the activity of neuron B, it will be even easier in the future for A to activate B
- 'cells that fire together wire together'
- tldr: co-activation of 2 events leads to those events being 'paired up' in the nervous system

temporal contiguity

may be necessary, but is not sufficient

- blocking and truly random control demonstrates event needed

blocking

- tone -> food -> salivate

- tone + light -> food -> salivate

- if sufficient, turning on light alone would lead to salivation, but it does NOT!

- assigning all credit of food to the tone (we do not learn about the light)

- A -> US, AB -> US, B -> ?, we do not learn B

blocking and truly random control

instances of NOT learning just because 2 stimuli are paired

truly random control

- tone -> food (around 10x)

- but, giving food in between without sounding tone (food = 'free')

- in this case, tone alone does not produce salivation

- assigning all credit to chamber that releases food, not the tone

Pavlovian conditioning with FEAR

both CONTEXT (chamber) and CUE (tone) are related to expectations of a shock (fear response)
- fear response = freezing

what happens if we eliminate hippocampal neurogenesis in the Pavlovian fear conditioning experiment?

context conditioning is impaired, but not cued conditioning

- hippocampus mediates recognition of where you are

extinction

cues that were previously used to predict shock no longer predict shock, and behavior replicates this (by not freezing to tone)
- tone + shock in Context A -> freezing to tone
- tone + NO shock in Context A -> stop seeing freezing to tone

after extinction occurs, what happens when you put mouse in Context B (or in Context A after a delay of no shocks)?

we observe freeze response to the tone, indicating that association remains

does extinction cause forgetting?

NO! extinction does NOT cause organism to forget learned behavior

long-term potentiation (LTP)

an increase in a synapse's firing potential after brief, rapid stimulation. Believed to be a neural basis for learning and memory.

explanation of how LTP works

- ‘deliver a tetanus’ to A (aka drive the hell out of A neurons, causing B neurons to fire / have large response)

- after driving A neurons strongly (high frequency stimulation), deliver just a SINGLE stimulus to A neuron and see what happens in B

- larger response produced in B neurons (lasts for minutes to hours to days)

- INCREASE IN SYNAPTIC STRENGTH

- measuring through electrode: getting summed EPSPs using local field potentials

specific diagram of LTP case in a mouse

- Structure A = hippocampus

- Structure B = amygdala

- slice: small bit of neural tissue (without interference from other brain parts)

- stimulate A, record potential in amygdala (B)

- found that driving presynaptic neuron causes drive in postsynaptic neuron as well

typical response of a cell to a stimulus

- presynaptic neuron dumps out glutamate

- glutamate binds to ionotropic receptor AMPA, causes sodium (Na+) to enter cell (depolarization), causing EPSP

NMDA receptor

- has magnesium bound to it (which blocks glutamate binding)
- ligand-gated AND voltage-gated

what changes in the cellular response when an LTP occurs (when 'driving' presynaptic neuron)?

- presynaptic neuron dumps out a LOT of glutamate
- glutamate binds to AMPA, releasing a lot of Na+ and depolarizing the cell (more +)
- ball of magnesium 'pops' out due to depolarization of cell, so glutamate can bind to NMDA
- increased concentration of Ca2+

steps of cellular response to LTP once Ca2+ enters the cell from NMDA binding

1. increase in intracellular concentration of Ca2+ ions
2. protein kinases activate, cause phosphorylation of proteins
3. activated kinases bind to CREB, which triggers immediate early genes
4. IEGs code for transcription factors that enter the nucleus and regulate particular late-effector gene expression
5. transcription of LEGs leads to synthesis of proteins
6. proteins transported down axon and into dendrites

is protein synthesis produced from LTP?

yes

idealized learning curve

- increase in exposure to contingencies -> increase in learning
- amount of learning diminishes with additional training (curve flattens)

Rescorla-Wagner model

'classic' model of Pavlovian conditioning

- describes change in strength of association

- Equation: ∆V = a*b*(L-V)

∆V in Rescorla-Wagner model

change in associative strength

a in Rescorla-Wagner model

salience of CS

b in Rescorla-Wagner model

salience of UCS

L in Rescorla-Wagner model

maximal associability of CS and UCS (contingent relationship between these 2 events)

V in Rescorla-Wagner model

current strength of association between CS and UCS (what is predicted)

learning (∆V) primarily depends on...

the difference between what is expected (V) and what actually occurs (L)
- (L-V) part of equation = the 'surprise'

changes in salience (a & b) modify...

strength of learning to a lower degree

dopamine neuron activity during learning: do dopamine neurons report an error in the prediction of reward?

dopamine activation drops when reward does not come when expected

- when no CS, dopamine linked to surprise of the reward

dopamine playing role of error detector (L - V) in Rescorla-Wagner model

there is a temporal (time) expectation
- time is learned as a part of the association between the CS and UCS
- no role of time in Rescorla-Wagner

timing effects in eyeblink conditioning

timing between CS and USC increases (delay) -> synaptic/learning strength decreases (weaker and slower)

- matches LTP

- mediated by cerebellum - no dopamine input

- blink in anticipation of a puff

relationship between TIMING of presynaptic and postsynaptic activity & LTP/LTD (STDP)

maximum LTP/LTD when presynaptic activity is right before postsynaptic

- LTD = long-term depression

phases of learning

1. acquisition / encoding
2. consolidation
3. retrieval
4. reconsolidation

1. acquisition / encoding

short-term LTP
- NO protein synthesis
- happens within 1/2 hour

2. consolidation

long-term LTP
- protein-synthesis dependent
- after many hours
- change in synaptic strength (increasing gene expression)

3. retrieval

expression of learning
- test response to cue
- association between CS and UCS can fluctuate as a result

Anisomycin

a protein synthesis inhibitor, blocks learning when given at the time of learning (or immediately after)

protein synthesis inhibition (using Anisomycin) following initial learning or following retrieval impairs...

subsequent performance

- day 1: encoding and retrieval, no consolidation

- day 2: if given Anisomycin on day 1: do not freeze (association was not made). if given vehicle on day 1: freeze (association was made)

- day 3: if given Anisomycin on day 2: must re-learn, even if previously given vehicle; if given vehicle on day 2: learn, even if previously given Anisomycin;

- note: testing at 4 hrs after Anisomycin on day 1 will show all rats have learned via protein-synthesis independent short-term LTP-like processes

where is memory 'stored'?

distributed storage; depends on the system used for the process

the amygdala is memory storage for...

fear conditioning

the cerebellum is memory storage for...

eyeblink conditioning

the striatum (basal ganglia) is memory storage for...

sensory-motor habit

the cortex is memory storage for...

declarative memories

which structure acts as temporary storehouse or address book?

hippocampus
- also involved in spatial memory

different brain structures firing for different stimuli

operant conditioning

a type of learning in which behavior is strengthened if followed by a reinforcer or diminished if followed by a punisher
- habit (striatal) vs representational (cortical / hippocampal)

T-maze

maze type that involves an alley ending in a "T" shape, giving the animal two path choices to reach food in goal box
- over trials, animal learns to run up and go left

procedural (motor) learning in the T-maze is mediated by what structure?

the striatum

spatial (location) learning / making cognitive maps in the T-maze is mediated by what structure?

hippocampus / place cells

place cells

type of cells found in hippocampus whose activity becomes associated with particular parts of a familiar environment

grid cells

neurons that respond when an animal is in particular locations in an environment, forming a repeating grid-like pattern
- fire when cell goes into a new space (creating a map / spatial framework)
- picture you are standing on graph paper and moving around the different squares

head direction cells

neurons that fire based on which direction an animal is facing

do place fields shift?

yes, they shift with shifts in distal cues
- ex: shifting with black 'curtain'
- oriented in relation to various landmarks

place fields are ___ over time

stationary

basal ganglia as a non-pyramidal motor system

- bi-stable membrane potential in Striatal spiny neurons

- 10,000 - 30,000 separate cortical inputs

- DA-mediated LTP/LTD

- striatal neurons can function as “perceptrons” - encode sensory response characteristics

- Beiser and Houk (1998) proposed that this circuit could mediate sequential behaviors

what happens when you flip the T-maze 180 degrees?

- running to star = place-based response (hippocampus dependent)

- running away from star = stimulus-response based (Striatal dependent)

- note: previously reinforced behavior is up and left

why do rats use different strategies when flipping T-maze 180 degrees?

individual differences
- depends on SIZE of structures (hippocampus and striatum)

does response (habit) learning or spatial (place-based) learning take longer to achieve?

response / habit learning

which structure is used more in early training?

hippocampus (spatial, place-based learning)

which structure is used more in late training?

striatum (habit learning)

effects of lesions after different amounts of training: EARLY in training

- Lesion hippocampus = animal will drop to chance behavior (not know where to go)

- Lesion striatum= place-based response

effects of lesions after different amounts of training: LATE in training

- Lesion hippocampus = continue to see response-based path

- Lesion striatum = animal switches back to place-based strategy

which structure is involved in episodic memory?

hippocampus

- involved in general representation of self

- lesioning = cannot form new episodic memories

- where memories are processed in order to be stored, not where long-term memories are actually stored

patient H.M.

- had severe epilepsy

- lesioned hippocampus

- could not form new episodic memories, but did not lose memories he had stored before the surgery

anterograde amnesia

an inability to form new memories

retrograde amnesia

an inability to retrieve information from one's past

declarative memory

- learn fast, flexible, forget easily

- brain areas = hippocampus and medial temporal lobe

procedural memory

- longer to learn, specific, retain over time, motor & perceptual learning

- brain areas = cerebellum & basal ganglia