PSYCH 371

midterm 1 cutoff: 214 midterm 2 cutoff: 437

Donald Hebb

neurons that fire together wire together

Eric Kandel

studied aplysia to understand habituation

learning

process of acquiring new information

memory

persistence of learning in a state that can be revealed at a later time

neurobiological approach

exprerience -> neural systems -> synapses -> molecules -> behaviour

Aplysia californica

sea slug model organism discovered by Darwin on his voyage

aplysia as a model organism (4 characteristics)

1. fewer neurons than most vertebrate species

2. soma are large and organized in ganglia

3. same neurons can be identified across experiments

4. can learn simple and reliable behavioural responses

non-associative learning

learning without a strong causal relationship (habituation, sensitization)

habituation

becoming less sensitive to a stimulus over repeated exposures, form of long-term memory

sensitization

becoming more sensitive to a normal stimulus in the presence of a noxious stimulus

associative learning

learning influenced by a causal relationship

classical conditioning

example of associative learning in which a neutral stimulus evokes a conditioned response

association by contiguity

natural organisms infer relationships between things that happen close together in space and time (proposed by Aristotle and Hume)

siphon-gill reflex

poking the siphon of an aplysia causes it to withdraw its gills, subject to habituation

siphon-gill reflex habituation circuit

~24 sensory neurons, ~13 motor neurons, excitatory and inhibitory interneurons, presynaptic inhibition, homosynaptic reflex

vesicle numbers ___ as a neuron becomes habituated to the siphon-gill reflex

decrease

homosynaptic mechanisms of learning

two cells, one synapse

tail shock reflex

small electric shock (noxious stimulus) to the tail sensitizes aplysia for days

heterosynaptic mechanisms of learning

multiple cells, multiple synapses; modulatory interneurons synapse onto terminals of sensory neurons

ionotropic receptors

neurotransmitters allows ions to flow through a channel

metabotropic receptors

neurotransmitters cause signalling cascade with enzymes or G proteins

modulatory interneurons release ___

serotonin

actions of modulatory neurons (5 steps)

1. serotonin released from modulatory interneurons activates G protein

2. ATP is converted to cAMP

3. cAMP allows calcium to flow into the cell

4. PKA causes phosphorylation cascade that leads to calcium influx and potassium outflow

5. neurotransmitters released from sensory neuron to open sodium channels in motor neurons

classical conditioning in aplysia

pairing a noxious tail stimulus with a neutral mantle stimulus eventually conditions a retraction response to mantle stimulation

CREB

cyclic response element binding protein; involved in transcription and translation of genes involved in long-term memory

NMDA receptors

coincidence detectors, require glutamate binding and depolarization to remove magnesium block

synaptic adaptation at the dendrite

calcium influx at NMDA receptors lead to long term potentiation

long-term changes in neural circuits require ___ protein synthesis

de novo

immediate early genes

genes that rapidly adapt to stimulation without de novo protein synthesis

arc protein

immediate early gene expressed with learning; functions as a memory snapshot

four Cs of memory research

connection, cognition, compartmentalization, consolidation

ecphory

retrieval cues reactive neurons to elicit memory retrieval

engrams

the pattern of neural activity that contributes to the formation of a memory

Sheena Josselyn

presented modern definitions for "ecphory" and "engrams"

The Encoding Specificity Hypothesis

memories are best recalled when retrieval cues overlap with training cues; proposed by Tulving

Godden and Baddeley experiment (1975)

scuba divers learned lists on land and in water to test The Encoding Specificity Hypothesis; found that retrieval is best in the same context as learning

neurobiological mechanism of recall

memories are stored in engrams, retrieval cues reactivate engrams (ecphory)

Engram Encoding Specificity Hypothesis

high congruence between encoding and retrieval conditions reactivates engrams and leads to successful recall

plasticity products

mRNA and proteins produced from nucleus and sent back to dendrites during a learning event

neuron ablation

"deleting" neurons to influence memory

Josselyn's fear conditioning

cause a fear response in a mouse, then ablate certain neurons to alter the response

optogenetic stimulation

exciting or inhibiting neurons by shining a specific frequency of light on them; allocates them to encode certain memories

non-mnemonic context

absence of conditioned stimulus

non-allocated context

presence of only conditioned stimulus

allocated context

presence of neutral and conditioned stimulus; tests for learned fear

state-dependent memory retrieval

recall is strongest when internal state is the same during encoding and retrieval (ex. having caffeine to study and then again during a test)

retrieval cue similarity

similarity of retrieval cue during learning and memory testing determines retrieval via engram reactivation

cFos staining

technique of staining recently activated neurons to visualize engrams (shows which neurons were active in a certain response)

memory recall (does / does not) depend on number of neurons active in the amygdala

does not

memory recall (does / does not) depend on number of neurons active during the memory test

does not

memory recall (does / does not) depend on the specific neurons activated in learning/ encoding/ retrieval

does

GFP tagging

using green fluorescent protein to visualize a gene of interest

hierarchy of neuronal organization

molecules -> single neurons -> neuron pairs -> neuronal ensembles -> brain systems -> behaving organism

connection

memory organization in cells, synapses, and circuits

compartmentalization

memory organization in brain systems

cognition

behavioural and psychological expression of memory

consolidation

storage and long-term transformation of memory

Hermann Ebbinghaus

discovered the forgetting curve and spacing effect

memory results from ___

changes in strength of synaptic connections at specific loci

hippocampus

large, segmented structure located in medial temporal lobe

dentate gyrus (DG)

one of two interlocking "C" shapes of the hippocampus

cornu ammonis (CA)

one of two interlocking "C" shapes of the hippocampus; composed of CA1, CA2, CA3

Terje Lomo

observed that repeated tetanus stimulation resulted in increased EPSP slope (LTP)

parallels between LTP and memory (5)

prominent feature of hippocampal physiology, develops rapidly, long-lasting, specific, associative

associative learning with LTP results from ___

sufficiently strong stimulation

in order for associative learning with LTP to occur from weak stimulation ___

it must be simultaneously stimulated with strong input

glutamate

primary excitatory neurotransmitter involved in LTP; high concentration in hippocampus

receptors that respond to stimulation with glutamate (2)

AMPA, NMDA

if you apply APV at the time of stimulation ___

LTP cannot occur

if you apply APV after the time of stimulation ___

LTP still occurs because NMDA receptors already opened and triggered signalling cascades

double gating of NMDA receptors provides LTP with the properties of ___ (2)

specificity, associativity

calcium entry is ___ but not ___ for LTP

necessary, sufficient

kinases stimulated in LTP (3)

PKC, CaMKII, MAPK

MAPK pathway in LTP

involved in protein synthesis

PKC and CaMKII pathways in LTP

involved in AMPA receptor trafficking

AMPA receptors have ___ phosphorylation sites

3

AMPA receptor P1

PKC; Ser 818 anchors GluA1 to PSD

AMPA receptor P2

CaMKII; Ser 831 changes GluA1 channel conductance

AMPA receptor P3

PKA; Ser 845 traffics GluA1 to extrasynaptic region

CaMKII causes conformational change in catalytic domains by ___

autophosphorlyation

consolidation hypothesis

memories require an extended period of time to be long-lasting

de novo protein synthesis hypothesis

memories require new protein synthesis to be long-lasting

phosphorylated ___ leads to new protein synthesis in the nucleus

CREB

long term depression (LTD)

opposite of LTP; eliminates unnecessary connections to not oversaturate memory

low frequency stimulation induces ___

LTD

high frequency stimulation induces ___

LTP

spike timing dependent plasticity

time between pre-synaptic and post-synaptic stimulation determines if LTP or LTD occurs

LTP is a ___ phenomenon

laboratory

downside of LTP in the lab

laboratory stimulation is significantly stronger than physiological stimulation, increasing prominence of results

how to observe LTP outside of the lab

observe and/ or interfere with molecular cascades when an animal is learning

ways to prevent LTP (2)

use APV to block NMDA receptors, use anisomycin to block protein synthesis

factors that increase difficulty of observing learning (2)

potential simultaneous positive and negative synaptic weight change, impossible to observe entire brain at once

mice/ rats learn better in an ___ environment

enriched

trace conditioning

form of classical conditioning in which conditioned stimulus and unconditioned stimulus are delayed for an interval of time

during trace conditioning, a conditioned response occurs during ___

the trace interval

rats/ mice cannot perform trace conditioning when their ___ is removed

hippocampus

there is a/ an ___ in dendritic spine density when animals perform trace conditioning

increase

if ___ are blocked, animals do not learn by trace conditioning

NMDA receptors

reaching tasks change synaptic efficacy via ___

motor learning

___ learning can occur unilaterally

motor