• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/175

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

175 Cards in this Set

  • Front
  • Back
how to confirm the existence of a drive state?
- test multiple ways to deprive
- are there many independent responses to deprivation?
What is drive theory (4)?
- animals have innate drives: hunger, thirst, sex
- when homeostasis for these is disturbed animals become tense
- motivation is to satisfy these drives, then they return to baseline
- there is no learning in the S-R paradigm. it is simply drive that influences behaviour
What is incentive theory ?
- animals do things based on the current value of the reinforcer (in its specfic context)
- the value of the reinforcer is changed by motivation

- how to test this?
1) reward devaluation (pre-feeding animals)
2) change the value of an outcome, and let allowing the animal to re-engage actions
Balleine and Dickinson 1995 (incentive learning)
- With limited instrumental training (120 presses), re-exposure to the food (incentive learning) in a sated state devalues the food during testing ONLY IF the rat is sated when tested. If the rat is hungry when tested, he will press for food a lot whether he was hungry when re-exposed or not. Re-exosure to the food in a hungry state will also "overvalue" the food, and a rat that is sated when tested will press a lot for it.

- This devaluation / "overvaluation" effect is not observable with extended instrumental training (360 presses). In this case, the main effect seems to be from the drive state at the moment of testing.

- The devaluation / "overvaluation" effect is also not observable with normal isntrumental training (120 presses) + 240 non-contingent exposures to the food. It thus only works after limited exposure to the outcome during training (whether it is contingent or not).

- If you give extended re-exposure to the food (incentive training) before testing, the rats become susceptible to the incentive training even after extended instrumental training (360 presses).

- There was no difference in the magnitude of this effect whether the rats were re-exposed to the food in the operant chamber or in another location, which means that incentive learning generalizes to different contexts.
What is the central motive state?
its part of the S-(CMS)-R paradigm that explains how an animal values a stimulus.

- CS doesn't only predict S
- after training, CS evokes CMS in response to S. Therefore, CS becomes an incentive

- the motivation that an instrumental performance provides can be controlled based on the state that the animal learns the outcome in.
habits (2)
habits form when goal directed behaviour over many trials leads to the same outcome

- once a behaviour has become a habit (controlled by striatum) then changing the value of the outcome doesnt change the behaviour
Tony Dickinson: the value of food must be learned separately under every motivational state (t/f)
true. so if you learn the value of chicken wings when hungry, you still dont know the value of the chicken wings when you're full.
the role of different brain parts in motivational behaviour: striatum, NA, amygdala, hippocampus, MPFC
SM cortex > dorsolateral striatum = habit formation

MPFC >dorsomedial striatum = goal driven behaviour

VTA > NA = codes the value of a behaviour (rewarding/aversive)

amygdala - real time comparison of motivational value based on previous experience

hipp - important for coding the context of a reward (where, how, etc)
motivational control of instrumental performance depends on ______________________
incentive learning
how dickinson (1987) shows support for incentive theory (4)
- pre-feeding before the test and not feeding before the test result in the same # of level presses during the test.

-if drive theory were true, the animals would have more motivation when hungry

- saccharine is non-nutritive so it didnt have impact on motivational state

-pre-feeding an animal who learned a task in a hungry state made the instrumental response lower (because the animal doesnt know the value of the food in this pre-fed state)
what is incentive learning influenced by? (dickinson 1995)
- amount of instrumental training (how many trials)

-amount of preexposure incentive learning (how many trials in that state)
2 process theory (4)
1) escape/avoidance response learning phase

2) removal of a conditioned fear (through the avoidance response) is rewarding
> this is an example of reinforcement without the US reinforcer

- if you block the avoidant response, stress increases

- the world is composed of aversive and rewarding stimuli
Bolles SSDRT (3)
- species specific defensive response theory

- different levels of imminent threat lead to different behaviours (escape, avoidance, etc.)

- increased fear means an increased change in response

- certain species evoke fear at sub-threshold stimuli compared to other species (ex: snakes vs. dogs)
2 pathway thepry of amygdala
inputs:

Thal > lateral amygdala (subcortical pathway, quick and undetailed sensory info)

Thal > Hippocampus > lateral amygdala (memory to serve fear, longer term, more detailed)

outputs:

- leave via central nucleus
- to stress hormones, parasympathetic, emotional behaviour, reflex activation
urbach wiethe disease (2)
- calcification of amygdala
- cant recognize facial expression of fear
gaze direction and amygdala activation
- averted gaze increased activation
areas implicated in response to face and body expressions of fear, fear vocalizations,
FFA and EBA (extrastriate body area)
amygdala response is best to which emotions? (2 points). support from where (4)
it responds to strong facial emotional expressions whether positive or negatively oriented.

HOWEVER
it responds across all modalities to exclusively fear, probably because fear is one of the most evolutionarily useful memories

support from:
- face recognition studies
-body language
-vocalization
-music
why cant people stop their addictions (2 models)
model 1
- drug use leads to tolerance and withdrawal making abstinence unpleasant
- fits with drive theory

model 2
- addiction develops without experiencing withdrawal and vice versa, so it cant be just due to withdrawal symptoms
- deprivation can make cues more salient
- fits with incentive theory
dopamine
VTA to:

- NA (ventral striatum)
- frontal cortex
- dorsal striatum
-
symptoms of PD (5)
- impaired initiation of movement (akinesa)
- reduced amplitude and velocity of movement (bradykinesa)
- micrographia
- muscular rigidity
- tremor

*50% more frequent in men
-age of onset (~60), 1%
parkisonian personality
- due to lack of DA in some areas
-
anhedonia hypothesis, low and high dose DA
dopamine mediates feelings of pleasure

1) low dose DA - causes incremental increases in behaviour that stay steady

2) high dose DA - quick increases in behaviour, followed by down regulation that makes you want more
dopamine functions
- response to sensory stimuli

- facilitates response to rewards
APTD
acute phenylalanine/tyrosine depletion
- these are the AA that make DA

- reduces catecholamine synthesis
-decreases DA levels in the brain
3 locations of drugs of abuse impact on DA
1) INHIBIT GABA cells and synapses that inhibit DA cells in the VTA
2) EXCITE DA cell bodies in VTA
3) EXCITE DA synpases in NA (coming from VTA)
summary of drugs impacts (3)
1. increased DA in NA
2. DA increases behaviours when rewarded
3. BUT the rewards themselves are not more pleasurable
drug euphoria & dopamine
decreased dopamine does not have any effect on drug euphoria (how good the drug makes you feel)
reward seeking behaviours & dopamine (2)
decreased dopamine causes people to work less hard for rewards.

- it doesnt change the value of the reward itself.
fMRI (2) vs. PET (1)
fMRI
- shows oxygen take up (less indicative)
- more blood flow, more oxygen consumption, weaker BOLD signal

PET
- shows glucose metabolization (more indicative)
functions of the basal ganglia (4)
1) select appropriate actions (reward learning)
2) inhibit inappropriate actions (punishment learning)
3) learn to match actions to context
4) set the current level of motivation/drive
parallel pathways of basal ganglia (4)
motor, cognitive, visual, affective
connections b/w BG and cortex (3)
association cortex -caudate head
sensorimotor cortex - putamen
limbic cortex - NA
implicit v. declarative learning locations in brain
declarative - hippocampus

procedural - striatum
DA's function as a signal / relation to reward
error signal for reward. it predicts rewards (ie. after S-R pairing, DA only released with the CS, not with juice anymore). it is NOT an indicator of reward having occurred.

- is a learning signal that shapes behaviour and promotes motivation
Parkisonian personality (6) vs. Novelty seeking personality (7)
Parkisonian personality
- rigid
- introverted
- compulsive
-slow-tempered
- dont usually smoke or drink
- dont seek out novelties

vs.

Novelty Seeking Personality
- impulsive
- fickle
- excitable
- quick-tempered
-extravagant
- linked to impulse control disorders and addiction
- elevated DA is what causes the impulsivity
impulse control disorders (5)
- high DA levels (sometimes in people being treated for Parkinsons)
- patholigcal gambling
- hypersexuality
- compulsive eating
- compulsive shopping
DRG neuron
- carries
first vs. second pain
- first pain: A delta fibres: sharp, pricking pain

- second pain: C fibres: slow, burning, pain
how does sensitization happen? (3)
- inflammatory soup: histamine, bradykinin, 5-HT, prostaglandin, ATP, and H+ act on nerve endings at primary afferents (sensitizing them)

- this acts through build up of 2nd messengers that initiate transcription of recptor protiens and pphylate ion channels

- substances such as Substance P, and CGRP are released from the nerve endings, acting on mast cells and blood vessels to produce neurogenic inflammation
what is projected pain?
when you hit your funny bone, it activates neurons along their axons, so the brain interprets the pain as coming from the place where the axon comes from (your hand). this is why you
3 types of efferent neurons for pain
1) A beta - only input from somatosensory > synpase onto WDR neurons and activate interneurons that inhibit them. also synapse non-nocioceptive projection neurons.

2) C fibres > synapse onto WDR neurons exciting them, and inhibit interneurons that would stop the projection neuron from firing.

3) alpha delta fibres (conduct quick sharp pain)
3 pathways of the anterolateral tract (3)
LATERAL GROUP

- spinothalamic (sensory pain)

MEDIAL GROUP

- spinoreticular (arousal)

- spinomesencephalic (emotional, affective pain)
wind up
- high intensity, high freq nerve stimulation leads to bursting activity that outlasts stimulation in WDR neurons

- WDR neurons are responsible to graded response to stimuli of increasing intensity
pain inhibition pathways
1. PAG > brainstem > spinal cord (inhibit projection neurons)
the order of testing effect is a type of _____________________. explain it
- socially mediated contagious pain hypersensitivity
> has behavioural synchrony, and increases overall pain
> through vision

- mice showed more pain after watching the others go through the same effects
> mice alone in a holding cage did not
stress & empathy
stress blocks empathy, reduces pain

- this is why stranger mice show less pain than mice alone, cause stranger mice cause stress in each other

- stress induced analgesia
social approach/ prosocial behaviour
is a behaviour that happens from a mouse not in pain to a mouse in pain. it is analgesic

- mice will untrap other mice that are locked in a cage.
cross-species pain mediation
- happens through olfactory cues
- it is stress related hormones
- mixed opid and non-opiod
the six reasons why mice are subject to anthropodenial
1. social communication before/after testing can affect pain sensitivity (“order-of-testing effect”)

2. social communication during testing in mice tested simultaneously can affect pain sensitivity (“empathy”)

3. female mice will approach cagemates in pain

4. social approach appears to be analgesic in and of itself

5. points 3 & 4 together could be construed as “prosocial behaviour”, and this has now been shown directly in rats

6. pain can be affected by chemosignaling, even cross-species
reality is constructed under 3 different time frames
1) memory - past
2) perception - present
3) simulation - future

-same type of stimulus (ie. pain) will engage similar brain regions for all 3
schemata
- an organized set of past reactions/experiences that you fit your memories of things to
- exist in animals

ex: verbal labels influence differential recall of the same stimuli (ie. gun vs. broom recall based on same picture)

- distortions caused by schemata:
- omission
-rationalization
- transformation
script
an episodic schemata

ex: eyewitness testimony
ex: hindsight bias (anchoring, adjustment)
spreading activation concept
- you remmeber one thing and other things that are semantically linked to that are also brought up in your working memory (but to a lesser degree)
reconsolidation
- The process by which a LTM becomes labile
again after reactivation, and undergoes another consolidation process
reminder induced updating
the fact that memories can only change if they are recalled, and require time to consolidate after the intrusion
three component reminder
1) context
2) stimulus (ie. a MC question)
3) partial cue (ie. experimenter theyve seen before)
repeated testing of a memory causes what?
schematization
hipppocampal plasticity after L
TM reactivation could go one of 3 ways in retrieval loss:
1) widespread memory deterioration

2) the loss of the hippocampal memory component

3) a disconnect between the hippocampal memory and cortical memory paths
imagining the future vs. prospective memory (as well as disorders, brain areas involved)
imagining the future
- facilitated by episodic memory

prospective memory
- remembering to do something at ta time in the future
- facilitated by semantic memory

DISORDERS
- korkasoffs amnesia
- MTL amnesia
- depression (less detail)
- schizophrenia
- older adults

*MTL, MPC and precuneus are involved
Hebb's STM-LTM cellular consolidation model (3)
1. a pattern of activity between neurons
2. this stays active after the experience (STM)
3. recurrent activity leads to changes in synapses so that the pattern can be created at a later time (LTM)
spine dynamics (3)
- part of the cellular consolidation model
- many new synaptic spines during learning
- only a few survive during consolidation
principle assumptions of systems consolidation theories (5)
¢ Anatomical position of hippocampus (central)

¢ Type of input the hippocampus receives (highly processed sensory input)

¢ Learning processes in hippocampus (impt for learning)

¢ Pattern separation in hippocampus

¢ Off-line interaction between hippocampus and neocortex
systems consolidation definition (4)
- process of a memory trace becoming reliant only on neocortical regions (HC independnet)

- STM > remote

- weeks-yrs

- memory traces shift from HC-dependent and neocortical dependent to just neocortical dependent
evidence for sytems consolidation (2)
- no impairment to memory if HC lesion is given several days after training for fear conditioning (kim & fanslow 1992)

- HM had intact procedural memory (skills) and semantic memory (facts)
theories of systems consolidation (3)
1) standard model
2) multiple trace theory
3) connectionist model
standard model of sys consolid (3)
1) encoding and cellular consolidation happens, making lots of connections within HC and between HC and cortex

2) most connections are labile during system level consolidation

3) systems level consolidation is complete, hippcampus is no longer connected, INTRAcortical connections form.
multiple trace theory (3)
1) encoding and cellular consolidation happens, making lots of connections within HC and between HC and cortex

2) some new connections are formed cross-cortically

3) systems level consolidation is complete, hippcampus is even more strongly connected, INTRAcortical connections form.
trace reactivation theory
- during sleep, recent memory indices are spontaneously reactivated in HC

- causes synchronous reactivation

- gradual formation of horizontal connections
connectionist model ()
- HC teaches neocortex over time since it forms connections faster, neocortex slower (has a lot of semantic info in conneections)
PR-STM
post-retrieval short term memroy.

NOT impaired by anisomycin injections
ACC in memory
ACC is incolved in consolidation and reconsolidation of recent and remote contextual fear memory
without hippocampal contribution, what happens to old memories over time? when reactivated>?
lose detail and vividness, become more semantic and gist-like

- when reactivated, become transiently dependent on HC again
allocentrism vs. egocentrism
allo: locations given based on external framework, independent of viewers POV
- task: morris water maze (can you cant tell left from right, but there are cues on the wall)
ie. using external cues


egocentric: locations are given based on viewer's POV:
task: radial arm task (cause all arms look the same)
ie. using left, right directions
place cells
- fire when the animal is in a specific location
- remap in a new context
path precesssion (3)
- animals enter a place field, place cells fire at peak of the natural HC oscillation (theta rhythm)

- future movements lead to earlier and earlier firings, matching pattern of theta rhythm but at a higher freq

- this codes temporal location (freqency of cells firing)
pattern separation (2)
- prevents interference in HC processing and allows us to discrimination between similar experiences

- similar info is stored in distinct, separate areas
pattern completion (2)
- degraded representations are filled in with previous knowledge

- allows generalization when given incomplete of noisy stimuli
attractor states (3)
- a network of neurons that are relatively stable, build from place cell networks

- cue info and the system responds with its most similar states (or identifies which states are different)

- these let pattern completion happen, or pattern separation
path integration (3)
- finding current position based on knowledge of previously know locations or cues

- uses both grid and place cells together

- grid cells provide a map for place cells to identify locations and therefore estimate distances
grid cells (3)
- found in hippocampus, fire when an animal moves around an area

- form a pattern of activation in the entire map that is polygonal (ie. like a grid)

- combine linearly to form PLACE FIELDS
why does the brain evolutionarily turn off regeneration?
- because its so difficult to copletely rewire, so some neurogenesis would probably cause more damage than it would repair
dolly's cells age and implication (2)
- same age as her "mother", so she died at the same time as her mother

- cellular aging is represented in the DNA
where are the two spots where neurogenesis happens?
dendate gyrus (for pattern separation)

and olfactory bulb (neurons come from lateral ventricle)
functional purposes of neurogenesis in memory (4)
neurogenesis allow us to show an improvement (causally, since destruction of neurons could be attributed to complex circuitry changing)

- learning and memory
-depression
-affilial attachment
- alcohol relapse
- etc.

BUT: THE NEW CELLS ARENT NECCESSARILY BEING PREFERENTIALLY USED IN NEW MEMORIES
different biochemical traces of memory, most volatile to least volatile (6)
- changes in PPHY state
(kinase/phosphotase)

- insertion and removal of membrane proteins
(requires some energy to reverse this)

- persistent activation of protein kinases
(different kinases are reversed differently)

- production of new protiens
(requires constant energy and persists based on lifetime of protein or mRNA)

-morphological changes at existing synapses

- new synapses
different ways how biochemical traces represent memory (4)
- diff trace in diff cells for diff memories

- particular traces for particular memories

- diff trace in same cell for diff memories

- diff trace in same cell for same memories (parallel)
STM maintenance & protein kinases (2)
CAMK2 - activated by Ca++, pphylates AMPA receptors

PKA (cAMP activated protein kinase), activated through G-protein coupled receptors, pphylates K channels for short term facilitation
different stages of protein kinase activation
1) inactive: catalytic domain is bound to the regulatory domain through a pseudosubstrate

2) active: regulatory and catalytic domains are held apart by 2nd messengers, anchoring proteins, and pphylation

how: cAMP pulls domains in PKA apart

3) persistently active: regulatory domain is detacted from catalytic domain, catalytic domain only regulated by anchoring proteins and pphylation

how: (ubiquitin-mediated degradation of regulatory subunit)
what does PKA do when persistently active? (2)
- catalytic subunit is a TF in the nucleus, and activates CREB

- at the synapse: maintains changes in synaptic strength by increasing transmitter release
PKA is important in which type of memory?
STM, because PKA inhibitors block memory for about 12 hours after learning but no more
CAMKII activation, persistent activation
- calcium + calmodulin bind to CAMKII and activate it

- persistent activation: done by pphylation, by a subunit (autoppphylation). only done for 2 (CANT be done for all 12). quickly afterwards, autopphylation site is attacked by phosphotases

-
FRET
used to measure conformational shifts in proteins (must put flurophores on measure points)

- low FRET in active CAMKII
- high FRET in inactive CAMKII (units close together)

SHOWED THAT CAMKII IS ONLY ACTIVE FOR 2 MINUTES AT A TIME
what does CAMKII do? (3)
- its translocated to dendritic spines

- CAMKII is bound to NMDA receptors (GluN2B subunit) and made constitutively active there

- general inhibitors of CAMKII are not good models for disruption of CAMKII cause of this special bond with NMDA

- CAMKII inhibitors block induction of LTP, not maintenence. once LTP is there, inhibiting CAMKII does nothing
>>> therefore AMPA receptors are the ones that make synapse stronger, NOT NMDA receptors.
CAMKII: impt in early LTP or late LTP?
NMDAr that cant bind CAMKII:

1) early LTP is BLOCKED
2) late LTP is reduced

- no CAMKII in spines
- no spine stabliization (new synapses do not stay)
- small reduction in LTM
CAMKII activation main effect
- insertion of AMPA receptors containing GluA1 (through a complex mechanism)

- knock-in mutations against CAMKII make learning more difficult, but once learning occurs, memory is not effected
why do memories persist over long periods of time? (3 models)
- memories are contiually being reinforced (sleep, recall, but if this were the case, why are some of our strongest memories the oldest ones?)

- memories are stored at new synapses that become stable over time
but: not only this, because molecules can mess with memory

- memories are stored by active memory traces
but: can molecules really last that long?
early vs. late LTP
EARLY LTP
- early LTP is after 1 train of stimuli
- GluA1 is important
- conserves LTM but not STM (in navigation)

LATE LTP
- late LTP is after multiple trains of stimuli
- uses GLuA2 receptor

BOTH
- may be antagonistic to each other
- have separate pathways
correlation of LTM with which LTP? (3)
late LTP induction (two forms: one that requires protein synth vs. prot synth + transcription)

- this was found by using anisomycin to block protein synth and actinomycin to block transcription
>> these only block the initiation of LTP
ZIP is a _______ inhibitor which blocks _________
PKMz

- MAINTENENCE of late LTP (24hrs)
- erases memory (conditioned avoidance)

NOT due to deficit in recall because PKMz could be injected and washed out before a memory was tested
PKC vs. PKM
- PKC is found in two forms, zeta and ioda.

- PKMz looks the same as the catalytic unit of PKC, but does NOT come from the same mRNA
> the mRNA of PKMz is preferentially upregulated after LTP

- PKMz accompanies the PKCz NOT PKCi
which memories are sensitive to ZIP? (7) which arent (
SENSITIVE:
- taste aversion
- auditory and contextual fear conditioning in LA
- Morris water maze: some loss
- Radial arm maze: reference memory affected
- neuropathic pain
- cocaine: potentiation
- sensorimotor

NOT SENSITIVE:
- identification of a novel taste
- contextual fear conditioning in HC
- radial mrm maze: no problem in STM
how does PKMz work? (3)
- increases AMPAr in membrane (not same mechanism as CAMKII)

- blocking endocytosis (with GluR23Y), cancels out effect of ZIP

- increasing levels (through injection) can increase strength of memories
Is ZIP specific to PKMz? (3)
- we dont know, cause knocking out PKMz didnt stop/erase memories

- ZIP could be targeting something else

- mice could show compensation through another memory molecule that can also be blocked by ZIP
how is PKMz made in Aplysia? (2)
- through the cleavage of other aytpical PKC into PKM during plasticity

- maybe compensation in vertebrates (after loss of PKM) is mediated by other atypical PKC cleavage
> this coudl explain why ZIP and other inhibitors block memories in cells without PKMz
Memory phases in sensorymotor neuron plasticity (4)
short term facil - (0-30mins): cAMP driven PKA activation that increases transmitter release

intermediate facil (30mins - 3hrs): independent of gene expression, depends on persistence kinases, require protein synth

long term facil (3h-1day): needs gene expression at induction, but not during expression

late long term facil (more than 1 day): formation and stabilization of new synapses

**DRIVEN BY 5-HT STIMULATION
LTM morphological changes (2)
larger active zones, more docked vesicles (go away after a while)

more synapses (dont go away)
serial vs. parallel memory formation
- serial traces:
- fits the consolidation model, building on top of the last method

parallel traces:
- three little pigs model
- start all 3 houses at the same time
- straw house is good while you are building the brick house
** would predict that you can make long term memory in the absence of short term memories
gene expression in LTM
- needed as a source of material for synapses

- but is not itself directive for formation of synapses, because transcription happens centrally and synpases form in localized places
what is CREB, what does it do (3)
- is a TF that is cAMP dependent
- blocking CREB blocks LTF without blocking STF
- CREB is normally bound in (with CREB repressor) >activated by 5-HT > causes gene transcription for synapse forming proteins

- creates LTM
what regulates CREB?
- pphylation (active with kinase = multiple exposure)
- diamerization with CREB repressor (active with removal of repressor = spaced training)

**So spaced trainign and multiple exposures both create LTF and allow CREB to bind genes and initiate transcription
CREB is important for which memories? (6)
- odour avoidance,
- faster LTM
- fear avoidance
- water maze tasks
-social recognition
- taste aversion
- water maze consolidation
making LTMs (and gene expression) has two qualifications
1) coincidental synaptic activation
2) modulation by NTs like DA, NE, ACh (ie. this is why we dont remember our dreams)
what happens when 5-HT is injected to the cell body vs. a specific synapse in Aplysia?
1) cell body: all synapses undergo LTF (even without STF or ITF)

2) synapse: the specific synapse undergoes LTF, new synapses are formed, and induces late LTF
morphological changes and central injection of active CREB
- you only need 5-HT pulses for 5 minutes at the synapse where you want to form a new spine
is the synaptic tag the memory itself or a general independent process? (2)
- in the PKMz model it is the memory itself

- in the Aplysia system, the synaptic tag is an independent general process

- late LTF requires consolidation (new growth, synaptic tag, nascent synpase formation, local translation of mRNA at the synapse) but NOT of the earlier memory traces
are there LTM without STM in vertebrates?
- SOME transgenic mice show deficiency in short term but not long term memory
gluA1 vs. gluA2
both are AMPAr subunits

gluA1 - impt for early LTP
>> mice without GluA1 have no LTP as adults
>> can still learn water maze (LTM w/o STM), but not tone conditioning (no STM OR LTM)

gluA2 - PKM-dependent late LTP (has tag for endocytosis)
radial arm maze to test LTM and STM
STM: food is only available the first time you enter an arm

LTM: food is only available in certain arms (spatial map)

STM & LTM: food only in certain spaces and only there once
Y maze to test LTM and STM
STM: put the animal in the maze 1 min after one of the arms was blocked off, if it goes to the one that used to be blocked off, you know they remember

LTM: same task but 24 hrs later after a lot of trials the day before
trace vs. delay conditioning (2)
trace conditioning (>100ms)
- period of time between end of tone and puff
>> requires hppcamus and PFC

delay conditioning (<100ms)
- puff is coincident/shortly after the tone
> doesnt require the hppcampus or PFC
input of info to cerebellum
TONE: A1 > pontine nuclei > cerebellar cortex (granule cells parallel fibres) > interpositus nucleus

PUFF: trigeminal nucleus > inferior olive (climbing fibres) > cerebellar cortex > interpositus nucleus
interpositus nucleus during eye blink conditioning
neurons increase in firing:

during learning
- the puff makes these cells fire

after learning:
- the cells fire before the puff
purkinje cells
- inhibitory GABA cells that prevent interpositus nucleus neurons from firing

- combination of CS-US arriving at same time in Purkinje cells causes depression from granule cells (CS) and decreasing firing of Purkinje cells
purkinje vs. interpositus cells function in eye blink
- purkinje: important in timing of response after stimulus

- interpositus: facilitates the actual S-R coupling
3 models for purkinje-IPN cell communication
1) inverter: more P cell activity, less interpositus nulceus (IPN) activity

2) t-type rebound: as soon as inhibition stops, IPN cells rebound

3) synchrony code: p firing in sync leads to firing of IPN cells
parallel fibres represented in culture
- represented by glutamate
- glu activates mGluR (g protein coupled)
- g protein causes Ca to enter the cell
- Ca entry and 2nd messanger from receptor activates PKCalpha
how LTD happens
- glu activates mGluR (g protein coupled)
- g protein causes Ca to enter the cell
- Ca entry and 2nd messanger (DAG) activates PKCalpha
- PKCalpha pphylates AMPAr
- pphylated AMPAr bind less to PDZ (scaffolding protein)
- AMPA receptors endocytosed
- AMPAr in purkinje cells are Glu 2 and Glu 3
regulation of endocytosis by PKCalpha (3)
1) PDZ is bound to specific AA acids at GluA2 terminal

2) PKCalpha pphylates the serine in AA residue

3) PDZ dips and GluA2 can be pulled out of the membrane
LTD in slices vs. culture
CRITICAL STEP IS THE SAME: pphylation of GluA2 at serine residue

culture:
- not much needed: calcium + gluatamate

slices
- SIDE REGULATORS: NO (inhibits phosphotases), requires more prolonged pairing of climbing & parallel, pphytase activity, calcium input,
why isnt Purkinje cell LTD a memory trace???
- you'd think that mGluR1 knockouts and others related to this pathway impair both eye-blink conditioning and LTD

- HOWEVER: LTD was blocked in P cells, but eye blink conditioning was perfect
used in which memory process?? : AMPA receptor insertion vs. removal vs. PKMz
- AMPA receptor insertion (E-LTP) (STM)
- AMPA receptor removal (LTD)
- PKMz (late-LTP) (maybe involved in spatial memory?)
according to mccaugh, do you define consolidation?
the period after learning in which retention can be:

- impaired by compomised neuronal/brain functioning
-impaired by interference from new learning
- enhanced by "memory enhancer"
draw systems consolidation flowchart map.

compare to extended model of HC memory consolidation map
well do it
amygdala circuits mediating emotional responding
CS+US > LA

LA > basal nucleus > basal ganglia (fear actions)

LA > central nucleus (fear reactions)
testing reconsolidation in LA (paradigm, conclusion)
paradigm:

CS-US x1 ------> CS |------> PR-STM -----------------> PR-LTM

- anisomyosin injection impairs LTM after reactivation, but not STM
- same result as anisomyocin under consolidation (after learning)
does reconsol need reactivation of memory? (paradigm, conclusion)
1xCS-US -----------> No CS |-----------> Test 2

- reconsolidation is predicated on reactivation
what happens if you inject anisomyosin 6hrs after reactivation?
very little prot synth is still going on, so the memory reconsolidation is not impaired as much as if you injected it right after activation
what is the control for making sure reactivation is neccessary for reconsolidation?
do the same paradigm that you used for the consolidation, but without the CS to reactivate it
hipppocampus & reconsolidation
CELLULAR
-undergoes cellular reconsolidation in dHC for contextual fear memories

SYSTEMS
-lesions to HC after 30 days of learning a memory do not impair that memory if recalled later
- but lesions tp HC 45 days after learning a memory DO impair the memory if it is reactivated on the 45th day
- if that is due to it being HC dependent still, then the lack of reactivation will still damage it after 45 days
how long does systems consolidation take? how about reconsolidation?
weeks vs. 2 days (each time)
cue induced amnesia
- Lewis' term for the field of reconsolidation back in the day
lewis' memory model
active memory
- s to hrs
- labile
- doesnt need RNA and protein synth

inactive memory
- days to wks
- consolidated
- requires RNA and protein synth

**FULFILLS SAME REQUIREMENTS AS MCGAUGH'S REQUIREMENTS FOR CONSOLIDATION**
ECT & reconsolidation
- reactivating a memory/emotion/thought and then doing ECT can get rid of or weaken those thoughts (we dont know the mechanism)
storage vs. retrieval problem
- is amnesia caused by a problem in storage, or a problem in retrevial?

- different for different memory systems
what is needed to express a LTM? (4)
- learning
- consolidation (reconsolidation)
- memory maintenance
- memory retrieval & subtle processes that this requires
traditional parradigm for amnesia

why retrieval failure cant be disproved with this
CS-US ---> amnesia induction ---> LTM ----> reminders (to test retrival's impact) ---- > test

retrival failure
- if there is recovery: this means that the cue brought the memory back, and so it was a retrieval failure all along

- if there isnt a recovery: maybe this is not the right cue to bring it back, but can't disprove retrieval failure on this basis
storage failure and spontaneous recovery
- spontaneous recovery was initially thought to be proof that storage failure didnt exist

- but amnesia NEVER completely destroys a memory

- and it is shown that spontaneous recovery can be based on external cues, that help REBUILD memories
- ie. reminders are not only recall signals, but they are learning signals
new paradigm for testing amnesia needs (2)
1) positive prediction for absence of memory
2) makes different predictions for storage and retrieval impairment
theory behind new paradigm for testing amnesia
- in HC, NMDAr are required for acquisition of a task the first time. if acquired again in a diff context, it doesnt need NMDAr. if it is retrieval failure, then the reminder cue shouldnt need NMDAr becuase memories aren't being "formed" theyre just being able to be retrieved.

if its a storage failure, blocking the NMDAr in the 2nd learning task should also block rebuilding of the memory, and result in the amnesiac not being able to recall.
new paradigm for amnesia (6)
1) allow first learning to happen
2) block consolidation with anisomycin
3) wait 5 days, then block NMDAr (with AP5)
4) start 2nd learning immediately while NMDAr are blocked
5) allow memory to consolidate
6) test memory
replicating the basic effect of NMDAr blocking (4)
- blocking NMDAr during first learning and NOT second, impairs the memory of A

- blocking NMDAr during second learning and NOT first does NOT impair memory for either A or B

- blocking NMDAr during BOTH impairs BOTH
results for the amnesia new paradigm experiment (4)
- NOT inducing amnesia or stopping NMDAr in 2nd learning results in no impairment

- NOT inducing amnesia but stopping NMDAr in second learning results in no impairment (since NMDAr are not needed in second learning)

- inducing amnesia but NOT blocking NMDAr during second learning impairs the first memory (duh), but the second one can form

and the key one:
- inducing amnesia AND blocking NMDAr during second learning impairs first AND second learning
- so NMDAr are important for second learning
Post-hoc caveat to new amnesia paradigm, how to test it, and results
can a retrieval impairment shift the system from NMDA dependance to NMDA independence?

paradigm: try extinction learning (retrieval impairment) between LTM A and context B instead of amnesia. block NMDAr before second learning

- results: blocking NMDAr had no impact on the results, because although retrival was imapired by extinction, the memory was sill fully stored, so NMDArs had no purpose
constraints of reconsolidation
- there is no universally effective reconsolidation procedure

-reconsolidation does not happen all of the time (boundary conditions: strength of training, pure space, sometimes extinction, age of memory, predictability)
theoretical implications of reconsolidation (2)
- bridges cognitive psychology perspective of memory with physiological psychology perspective

- after a couple of recalls of a memory, wouldn't all info be radically changed?
2nd order conditioning. is it serially or parallel connected to US? implications
1. CS1-US
2. CS2-CS1
3. CS2 is connected to US

SERIALLY
- impairment of CS1-US also destroys most of CS2-US
- impairment of CS2-US doesnt destroy CS1-US

THEREFORE
- only directly activated memories and their serial connections (if only connected to 1 thing) return to labile state
memory destablization define
- the process of making a consolidated memory labile again
- maybe its based on NMDA/AMPA receptors, because they are important for making learning > labile memory (before consolidation)
memory destablization & NMDAr
- ifenprodil (NMDA-NR2B blocker) BEFORE the CS will prevent reconsolidation, but after the CS, cant stop reconsolidation

- found that it is done by NMDA (NR2B subunit) receptors

- provides further evidence for lack of NMDAr involvement in conditioned freezing response (otherwise the NMDAr block would have affected the behavioural memory)
memroy destablization & AMPAr
- CNQX is an AMPAr inhibitor

-CNQX is applied right before memory reactivation

- it blocks the expression of freezing, but not the long term memory's sensitivity to anisomyocin
memory destablization vs. expression of a conditioned response (mechanisms)
In amygdala:

- done by NMDAr

vs.

-done by AMPAr
strength of training and memory destablization
- strong memories reactivated 2-7days after training are insensitive to anisomycin changes

- but reactivation 30-60 days after learning causes reconsolidation

- strong training is a boundary condition to memory destabilization

- more training downregulates NMDA receptors with NR2B in them

- this is mediated by dHC. lesions to dHC make reconsolidation of strong memories happen within only 2 days. so the hippocampus protects strong memories from reconsolidation for a while by downregulating NR2B subunits
clinical implications of understanding memory destablization
we can give NMDAr agonists to facilitate bringing back those bad memories (but then we would have to localize the agonists to those memories)
what is PTSD?
- trauma leads to release of stress hormones
- these hormones strengthen consolidation of the emotional memory of the event
- excessively powerful and persistent memory is too easily activated with consequent anxiety & dysfunction

PREDISPOSITION:
- lower function and volume of HC, lower volume of PFC
propanolol
- is a beta blocker (beta-andrenergic antagonist)

- has differential effects on emotional vs. non-emotional memories

-systemic propanolol blocks the consolidation of emotional aspects of memories by acting on beta-andenergic receptors in amygdala, but doesnt block contextual and episodic memories
ways to measure conditioned fear responses (3)
heart rate, skin conductance, corrugator EMG
drugs of abuse and reconsolidation
- maybe cravings can be reduced by extiction training when someone gets cues for a drug(reactivation)

- lowered mean craving, heart rate, and bP
forgetting curve
- done by ebbinghaus
- sketch it
theories of forgetting (3)
1) erasure
- direct destruction of memory

2) retrieval failure
- memory there but not accessible

3) decay
- memory is smeared (interference?) or broken up (trace decay?)

**95% of people believe in interference theory as of right now
novel location preference
- rats prefer to be around training objects that are in new locations (treat them as novel)

- this is a good way to study memory because if they dont remember, then everything is novel

- time the anmials spend moving around needs to be controlled for

- PKMz into hippocampus leads to memory loss if injected up to 34 days after sample
gluR23Y
a peptide that prevents memory erasure by binding to the tyrosine cluster in GluR2 tail, preventing it from being endocytosed
does forgetting facilitate new memories?
no

- there is usually not much interference between old and new memories
decay as an active mechanism
- blocking NMDAr during retention PREVENTS forgetting
- so NMDAr serve a function in forgetting

*specifically, its the NMDAr NR2B subunit ---- SAME ONE IMPLICATED IN MEMORY DESTABLIZATION
what is a cellular correlate of forgetting?
de-potentiation of LTP

- so the endocytosis of AMPAr is important to forgetting (mediated by NMDA NR2B subunit somehow)

- Chronic treatment with this peptide could retard onset of Alzheimers
alzheimer's is CAUSED BY forgetting
- forgetting is NOT A SYMPTOM of alzheimers. but maybe it is the root cause

- chronic treatment with peptide (GluR23Y) slows the onset of Alzheimer's dementia