PSYCH 371 MIDDY ONE

behaviour vs mind

behaviour is observable actions

mind consists of thoughts, feelings, etc. (subjective experiences)

study mind through observation of behaviour

neurobiology

study of structure & operation of the nervous system

behavioural neuroscience

study how the brain operates to produce behaviour

cognitive neuroscience

how the brain operates to produce mind/cognition

learning

interactions with the environment alter our behaviour

memory

retention of changed behaviour (learning)

first premise of neurobiology of learning and memory

the nervous system is entirely responsible for behaviour and mind

second premise of neurobiology of learning and memory

any modification of behaviour must be reflected in structural changes of the nervous system

connection

how units of the nervous system (neurons) are connected and interact

memory is in the synapse

cognition

memory is constrained by psychological aspects

you can exhibit knowledge without expressly behaving it

ex. Tolman’s rat mazes - rats were acquiring knowledge unknown to tolman

consolidation

process of memories becoming more permanent/long term

compartmentalization

different brain systems are responsible for different types of memory

aristotle

psych approach, associations are important

greeks used method of loci

ebbinghaus

forgetting, savings (relearning previously known info takes less time), massed (cramming night before) vs spaced repetition

used self as subject

psych approach

muller and Pilzecker

observed the importance of space after learning for consolidation - retention was lessened when that space was interfered with

rehearsal, interference and consolidation

psych approach

William james

different types of memory

habits vs memories

psych approach

pavlov

conditioned reflexes, S-R learning

driving force of behaviourism movement

psych approach

dualism

mind and body are entirely separate entities, the study of the mind is impossible because it is unobservable

materialism

current view, recognize the mind can be studied through behaviour

Ramon y Cajal

neuron theory

used Golgi stain to identify individual units

determined synapse the site of communication

neurobiology approach

Ribot, Alzheimer, Korsakoff

brain related memory disorders

recent memories more susceptible to loss than remote memories

neurobiology approach

Hebb

neuronal association

cells that fire together, wire together

neurobiology approach

Kandel

solidified theory that memory is the result of long-lasting synaptic changes

neurobio approach

Brenda Milner

studied H.M and memory systems

separation of declarative and procedural memories (compartmentalization)

neurobiology approach

soma

cell body of neuron

contains nucleus

controls protein manufacturing and directs metabolism

receives input

dendrites

input structure of neuron

if input large enough to reach threshold, AP generated

axon

output of neuron with 3 parts:

axon hillock where AP initiated

main axon: main tube part

axon branches connect to dendrites of next cell

synaptic button/terminal

at end of axon

contains neurotransmitters packed in vesicles which are released in communication with next neuron

Sherrington’s neuronal subtypes

sensory (receptors), motor (effectors) and interneurons (processors)

how is the resting potential maintained?

uneven distribution of ions across membrane-more negative INSIDE cell generates difference of -70mV

passive dispersion of ions (K, Na, Cl and Ca channels)

describe events of action potential

at resting membrane until electronic depolarization to threshold triggering opening of Na channels

lot of Na floods in, depolarizing cell

cell depolarizes by closing Na channels and opening K to let K out

brief hyper polarization when gates delay closing and too much K slips out

resting potential restored as ions passively redistribute

Ca role in synaptic transmission

Ca enters cell at synapse (triggered by AP)

acts as charge carrier and 2nd messenger

Causes ntmtr vesicles to fuse with membrane

ntmtrs release into cleft

ntmtr binds to post syn receptor, opening ligand gated channels

ionotropic transmission

fast, not as long lasting results

act via ligand-gated channels

excitatory: open depolarizing channels

inhibitory: open hyper polarizing channels

metabotropic transmission

slow but produce changes on cell that have longer lasting effects

changes metabolism of cell

temporal summation

multiple APs from SAME presyn cell occurring close together in time

spatial summation

multiple APs from DIFFERENT presyn cells occurring close together in time

simplest reflex circuit\`\`

sensory neuron > motor neuron

ex. patellar tendon reflex

next simplest reflex circuit

sensory neuron > interneuron > motor neuron

used when a decision needs to be made

ex. holding very hot but valuable item, decision to not immediately drop item

non-associative learning

habituation and sensitization

habituation

repetitive stimulation gradually produced less and less of a response

gradually learn not to respond to irrelevant stimuli

ex. perfume smells strong at first and then you become habituated

sensitization

strong stimulus increases amplitude of response to any other stimulus

ex. ptsd? - loud noise/fearful stimulus startles you and then you are more easily startled the rest of the day

classical conditioning

neutral stimulus elicits conditioned réponse after having been paired with unconditioned stimulus

ex. pavlov’s dogs

why is aplysia used as model?

simple adaptive behaviours

small number of CNS neurons (easily traceable)

soma are large for easy of manipulation and recording

identifiable neurons

gill withdrawal reflex

gill and siphon withdraw when provoked

when relaxed. aplysia extends gill and siphon

40 sensory neurons trigger release of glutamate to stimulate 6 motor neurons

habituation in GWR

GWR becomes reduced when stimulated multiple times

can be rapid (15 minutes) or lasting (up to four weeks when stimulated over four days)

modification presynaptic → reduction in amount of NTs released

homosynaptic depression

cellular circuit of GWR

sensory → interneuron → motor neuron → gill

but also sensory → motor neuron

homosynaptic depression mechanism

changes in number of ntmtrs reflect changes in presyn entry of Ca

isolation of Ca currents led to reduction in width of spike and Ca currents reduced

result: decrease in EPSP in motor neuron

also fewer sensory → motor synapses and docking of vesicles (anatomical change)

sensitization of GWR

tail stimulated with electric shock leading to increased response to additional stimulation

same cells as habituation (presynaptic)

heterosynaptic facilitation

how did Kandel know habituation/sensitization was presynaptic?

pharmacological receptivity did not increase between motor neuron and ntmtrs therefore not postsynaptic

mechanism of heterosynaptic facilitation

isolation of Ca currents lead to increase in width of spike, increase of Ca currents

result: increase EPSP in motor neuron

more sensory → motor synapses & docking of vesicles

tail sensory neurons facilitating interneurons

serotonin activates metabotropic receptor to increase post syn effect on motor neuron by:

inactivate K channels, activate Ca channels, mobilize NT vesicles

steps in heterosynaptic facilitation in GWR

1. serotonin release
2. Gs protein
3. ATP → cAMP
4. PKA


1. decrease K current by closing channels
2. increase Ca current
3. increase vesicle mobilization
5. increased NT release!

long term sensitization due to

maintenance of presynaptic facilitation and growth of new synaptic connections

mechanism of long term presynaptic facilitation

1. sufficient amounts of PKA (from adenyl cyclase)
2. MAPK
3. translocation to nucleus
4. activation of CREB, CRE gene expression


1. early: persistent activity of PKA
2. later: activation of proteins necessary for synaptic growth
5. maintenance of increased NT release

classical conditioning of GWR

alpha and differential

pair mantle stimulation (CS+) with tail shock (US) → elicits conditioned response (stronger)

siphon stimulated without tail shock (CS-) → elicits low response (no change)

positive CS

paired

classical conditioning circuit

similar to sensitization

siphon sensory neuron → motor

US tail sensory neuron → interneuron → motor

CS+ mantle sensory neuron → motor

mechanisms of classical conditioning

concurrence of activity in sensory neuron AND interneuron evokes greater facilitation

amplification of serotonin activation → increase of cAMP

greater facilitation of behaviour

steps of activity-dependent heterosynaptic facilitation (CC)

1. AP allows Ca facilitation of adenyl cyclase
2. 5-HT-Gs protein
3. adenyl cyclase


1. increase ATP to cAMP
4. PKA increase


1. decrease K current
2. increase Ca current
3. increase vesicle mobilization
5. A LOT of ntmtrs released

long term potentiation

a long lasting and activity dependent increase in synaptic efficacy due to coincidental activity in pre/postsyn neurons

same input yields bigger output

ex. practicing a dance over and over again it becomes second nature

LTP induction

presyn glutamate release and postsynaptic depolarization

can be blocked by preventing depolarization of postsyn cell

properties of LTP

co-operativity: threshold - probability of evoking LTP increases w strength of stimulation

associativity: can be evoked by paired stimulation of two different inputs (weak and stronger)

specificity: only synapses activated during stimulation train are potentiated

mechanisms of LTP induction

glutamate reaches AMPA and NMDA receptors

results in increases in postsynatic receptor responsiveness & numbers, presynaptic ntmtr release and greater synaptic contacts

larger response recorded for same input

AMPA receptors

AMPA increases membrane permeability to Na and K

if frequent APs stimulate AMPA enough, post synaptic neuron depolarizes

once Ca starts moving, more AMPA added to membrane

more receptors = increased postsyn senstivity

NMDA receptor

NMDA increases permeability to Na, K and Ca

Ca is blocked by Mg until postsynaptic cell depolarized

requires BOTH glutamate and post syn depolarization

how do we know Ca critical for LTPs?

Ca chelators block LTP induction, release of caged Ca induces LTP

LTP maintenance mechanisms

Ca activates protein kinases (incl. CaMKII and MAPK)

CaMKII (LTP)

activated by LTP-inducing stimuli

activation induces LTP while inhibition blocks it

undergoes autophosphorylation (no longer requiring Ca) which could maintain long-lasting LTP effects

MAPK (LTP)

activated by phosphorylation processes during LTP or Ca directly

inhibition blocks gene expression necessary for late LTP

phases of LTP

early/induction: NMDA receptor activation and Ca dependence

medium/expression: changes to receptors and release machinery and local protein synthesis

late/maintenance: genomic and anatomical changes

long term depression (LTD)

same input yields smaller output via denaturation of synapses (presyn w/out post syn or vice versa)

anti-hebbian (neurons that don’t fire together won’t wire together)

ex. use it or lose it

mechanism of LTD

decrease in NT release and receptor numbers

Mg blocks Ca so NMDA receptors never trigger additional AMPA receptors → less glutamate overall

enriched environment study

studied behavioural LTP

rats assigned to enriched environments were shown to have evoked bigger potentials

amygdala and conditioned fear

fear learning results in bigger potential to electrical stimulation

link between LTP and memory in a specific form of learning

motor learning and LTP

motor skills refined after repeated stimulation of reaching for food

synaptic plasticity generalizes to motor cortex and learning

evidence that LTP is involved in learning and memory

interference of LTP interferes w learning and memory

protein inhibitors interfere w memory

memory is impaired after induction of LTP

saturation of LTP impairs learning ability

hippocampal LTP and spatial memory

ex. spatial learning in morris water maze

NMDA was blocked/LTP genetically modified resulting in impairments of spatial learning

hippocampal LTP and spatial coding

study showed blocking of LTP resulted in place field instability

influence of genetics on learning and memory

production of intracellular machinery (proteins) necessary for EXPRESSION of behavioural modifications (learning)

moment to moment regulation of factors necessary to MAINTAIN modifications (memory)

disruptive selection

tails favoured

directional selection

one extreme favoured

selective breeding for learning behaviour

Tyron maze learning tests (interbred bright and dull performance)

concluded learning behaviours inherited - but unsure if it was due to other genes such as sight or tactile genes

protein synthesis role in long-term memory retention

experiment blocked protein synthesis after learning paradigm

acquisition and short term memory normal but long term memory abolished

conclusion: gene products necessary for maintained changes in nervous system?

Benzer fruit fly study

classically conditioned smell avoidance

flies choose to go to the odor that wasn’t paired with shock

learning index

fraction of organisms that learned minus fraction that didn’t

forward genetics

gene manipulation

breed mutants

test for abnormalities

map gene

problem: pleiotropy, hard to isolate for one function without hindering others

learning deficits in mutants

all involved with adenyl cyclase somehow

molecular and genetic aspects of neural change

activity dependent signalling leads to:

second messenger activation

post-translational activation

transcriptional activation: new proteins ensure continued physical and anatomical change

production of novel proteins: LT changes in physiology and anatomy

reverse genetics

target specific gene (hyp that its involved in learning and memory )

knockout/genetically modify it

assess behaviour

more specific than forward

thorndike

law of effect: rewarded bhvr is learned, punished bhvr is eliminated

skinner

used reinforcement

Skinner box - rat in box learned to press the lever to open the door so that it could get to food

operant conditioning

situation→response→consequence→result

learning environment, bhvr emitted, stimulus (either reinforcement or punishment), learning (either to perform or not to perform)

motivational state/drive

intrinsic conditions regulated by hypothalamus

ex. hunger, thirst, curiosity, mating

incentives

external goals/reinforcers

ex. food, water, good grades, mate

olds and milner

discovered the pleasure centre in the brain by repeatedly stimulating rats’ lateral hypothalamic sites

rat went crazy when allowed to self-stimulate

brain stimulation-induced reward

mesocorticolimbic dopamine system

self-stim activates dopamine release in NAcc

mesocorticolimbic dopamine system

ascending pathway from ventral segmental area to forebrain structures: NAcc & striatum, limbic structures, prefrontal cortex

modulation of self stimulation

increasing drives → lower stimulation freq gives high response

lesions of dopaminergic cells → no more self stim

drugs alter dopaminergic function → make harder to get reinforcer response

drugs of abuse

is dopamine a reward signal?

activity of dopaminergic cells increase to both rewards and non-rewards like unpleasant, noxious or novel stimuli

integration of input from multiple sites increases importance of stimulus

LTP in reward circuits

dopamine AND glutamate activate NMDA receptor

serotonin/Gs proteins activate receptor and convert to adenyl cyclase via phosphorylation

PKA

CREB/CRE

enhanced synaptic connections

LTP tells nucleus that the stimulus is important

associative cues in reward and addiction

ex a glass of beer stimulates striatum in alcoholics brain in a way that is unseen in non-alcoholics

ie. the stimulus has become a cue to stimulate cravings