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PS2061: The Remembering Brain - Coggle Diagram
PS2061: The Remembering Brain
Foundations
Physical Basis of Memory
Origins of Memory
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Associatism
Memo depends on linkages between pairs of events, sensations, or ideas
Proposed 3 principles of association
3 Principles of Association
Continguity
Frequency
Similarity
Aristotle's Empiricism
Learning the process of drawing info into mind
Mind a tabula rasa (blank slate)
Experience subsequently recorded
Plato Nativism
All knowledge innate
Learning not acquisition byt process of 'drawing out' knowledge
Basis of Memo
Nature & organisation
Timeless Puzzle
Intrigued philosopher, poet, scientists
Much what know built on ideas of Aristotle
Core q's remain
Learning & Memo (Squire, 1987)
Intrinsitcally linked
Learning the process of acquiring info
Memo the persistence of learning in state that can be revealed at later time
Physical Basis of Memo
Memo must be encoded by physical changes in brain
Can be captured by related concepts
Plasticity
Capacity for brain structure to change over time based on experience
Brain Plasticity
One of most fundamental properties of brain is capacity to change w. experience
Particularly true during early development but seen throughout life via host cellular & structural processes
Neurogenesis
New neurones in certain regions
Pruning
Removal of unused connections in brain
Synaptic growth
Changes in synaptic strength
Synaptogenesis
Formation of new synapses/synaptic growth
Changes may form neuronal basis of learning & memo
LTM Declarative
LTM Non-Declarative
STM
Realised in Brain
Memo systems considered to broadly align w. distinct brain regions/networks in classic view
Studies of plasticity provide insight into higher-level systems but provide only general mechanisms
Relates
Memory
Classic taxonomy proposes several distinct systems (Squire, 1986)
Declarative/explicit
Non-declarative/implicit
Memo central to sense of self
Understanding neurobio important for understanding who we are (Eichenbaum, 2001)
Engram
Phsycial trait/substrate memo in brain
Emerge from activity-dependent plasticity
Mechanisms
Synaptic Plasticity
Neural Connectivity & Memo (y Cajal, 1984)
Research focused on synaptic plasticity
One of first to theorise learning invove strengthening & weakenins of connections between individual neurones
Neurones dicontinuous units of info rather than strong set units
But question how
(James, 1980)
Speak against general idea that if two neurones active together tend to be stronger together in futire
Theory of Synatpic Plasticity (Hebb, 1949)
Hebbian learning = Learning that involve changes in connectivity strength
Neurones that fire together wire together idea
Learning
Event activate subset neurones/nodes
Reflect diff features of event
Repeated exposure further strengthn represetation
Re-exposure to subset re-activate whole event representation (pattern completion)
Means little bit of cue for vivid experience
Intutition
At moment is theory, so need to look at individual synapses
Hippocampus
Modern neuroscience made tremendous
Most research focused on hippocampus
Why Focused On
Weird & convoluted structure
Inputs & outputs well-defined
Has clearly stereotyped manner of activity
Mechanisms
Lomo investigate how high frequency stimulation to hippocampus input pathwaus influence firing in hippocampal pathway
Stimulate input pathway on pre-synaptic neurone & record on post-synaptic neorune
What Found (lomo, 1966; Bliss & Lomo, 1973)
Record excitatpry post-synaptic potential (response to stimulation)
Low level stim have low EPSP (low & stable activity)
High level stim (proxy to event will go on to remember, 1000s APs being fired in few) show increase response (tetanus) in post-synaptic neurone
After high frequency go back to low frequncy, but post-synaptic activity remain elevated (like it needs to remember that) & lasts for long time and may extend to weeks
Significance
Show growth/metabolic activity shown
Nerone Growth
More experimental control
Activity nodes & monitor specific synapses
Manipulate networks
Singificance
Show activity & arrangement of system & how it matters
Man
Link of Other Models/Approaches
Associationist models
Connectionist Models (weight changes based on neural activity, like real brains)
Long-Term Depression
Saturation Problem
If one form plasticity eventually all synapses saturated
Need other mechanisms that dampen
Long-Term Depression
Occur when synaptic transmission becomes less effective as result of recent activity
Pre-synaptic repeatedly active
Post-synaptic not respond
Is Synaptic Plasticity a Feasible Model of Memory
Assessment Criteria
Clear testable predictions to evaluate hypothesis
(Martin et al., 2000)
Allowed to see in live animal not just in vitro
Criteria
Detectibility
Does learning result in changes
Changes After Behav
Induced in mammalian brain & simpler invertebrate NS
Aplysia
Very compact, small, neatly arranged, simple NS
Neurones are largest in animal kingdom
Simple & logical reflext that can be modified by many types of learning
Partixcularly striking that scientists mapped each neurones involved in simple reflex
Circuit Level
Sensory neurone in diff areas (siphon/tail/mantle)
Maps to motor neurone
Modulatory interneurone
Gill withdrawal
Classical Conditioning in Aplysia
Protect from discrimination
When mild tactical stimulation withdrawal occur
1 more item...
(Murphy & Glanzmann, 1999)
See after learning = Increase in post-synaptic potential, learning increases leads to changes in plasticity
Applied NMDA antagonist = Blocks learning (no increased ESPS)
Form of learning cause exciteability changes that dependent
Significance
Show detectibility
Show anterograde altertion (prevent learning)
Anterograde Alteration
If somehow block plasticity can you block learning
Lesions
Good fow showing where learning occur
But destriy whole circuit not just mechanism
So need way to block mechanism specifically
Morris Water Maze
Rodents placed in pool, navigate to platform using landmarks in environment
Rodent dropped to diff parts on diff trials so extrapolate based on landmarks
Suggest specific to hippocapal learning
(Morris, 1989)
Examine role of NMDA receptors
Rats have NMDA antagonist/saline solution
Antagonist bind to recptor w/out. activiating it (prevent glutamate binding and tus hippocampal LTP)
Rats w. antagonist slower to learn platform location (performance slower), spend less time in target area (aimlessly wandering), impaired only in spatial learning (shows specificity of hippocapus), LTP completely abolished
Not same degree efficacy in antagonist
Retrograde Alteration
Does disrupting/erase LTP erase memo of event
Mimicry
If artificaially create synaptic changes can you create false memo of event even if it never happened?
Question is introduce memo test (engram) that never experienced & show it guides behaviour
Most stingent test of hypothesis
Optogenetics
Light sensitive proteniins allow researchers to activate specific nuerones w. infrared light, goal to control activity in some cells not others, can deliver molecules to some cells not others to activate them & figure out what happens if turn on/off (temporarily delete activity), identify specific cells in certain states
Enable precise manipulation memo circuits
Memo w/out Experience (Vetere et al., 2019)
Optogenetic stim for aversive pathway less likely to explore olfactory chamber
More/less time in chamber of smell stimulated w. even though never experienced
Significance
First proof that memo induced w.out experience
Questions
Does stimulating produce real sensation/trigger donwstream circuits involved in memory retrieval
Does VTA stim actually feel rewarding/aversive
Can false memories be truly experienced
Can it be extended to even more significant memories
Can be extended to humans
Does learning cause synaptic change
Does blocking plasticity prevent learning-
Does disrupting synapses after learning erase memo
Can synaptic changes create memo
Discussion Points
Do findings from simple organisms tell meaningul about human memo
Could LTP be nec
Is LTP Really Memo
Appeal of LTP (Morris, 1989)
Suggested has 5 properties that make it appealing neuronal model of memo
Appeal
Hippocampal
LTP key component of physiology
Highest density NMDA receptors
Decades work in humans & animals highlight region as important for ep
Patient LTM
Hippocampus removed
Catastrophic effects on memo
Rapidity
Can be induced v. quickly
Usually 1 min after tetanus
Important for rapid learning & encoding (one quick sig event enough to induce LTM)
Longevity
Can last several hours after single stimulation train
Can be seen weeks later is reminder stimulation applied
Stimulate again at later date re-activates
So can push out for weeks
Specificity
Only synapses activated/active synapses strengthened
Only synapses active during stimulation are potentiated
Neighbouring synapses even if on same neurone unaltered (Tao et al., 2000)
Mirrors specificity of everyday memories
Only remember specific elements present during event not everything
LTP provides potential cellular mechanism for selective encoding
Associativity
Closely timed events gain synaptic strength by association
Classic Studies (Bliss & Collingridge, 1993)
Weak input = Not product LTP on own regardless of stimulation intensity
Strong input = Induce LTP when stimulated above certain threshold
When poth inputs stimulated simultaneously LTP observed in both pathways (including weak one) = Associative by nature
Known as associative LTP
May mirror classical conditioning (Frey & Morris, 1997)
Neutral stimulus becomes meaningful when paired w. stronger one
Shows temporal coincidence
Associativity & Hebbian Learning
Associativity offers cellular model of Hebb's hypothesis
Repeated activation of pre-synaptic element
Participation in success of firing post-synaptic element
Only when both conditions met does connection strengthen
No. Neurones (Anderson & Trommald, 1995)
100 synapses need to be active at same time to fire hippocampal neuron
So Hebbian learning require coactivation of many neurones
Associativity shows many inputs can be integrated to fire post-synaptic cell
Molecular Basis of LTP
Relies on cascade molecular events that are becoming well-understood
Broadly increases efficacy of synapses in 3 particular ways
Ways
More receptors available
Retrograde messengers pass post to pre-synamptic neurone & activate more neurotransmitter
More neurotransmitter relased
Mechamisms
LTP in hippocampus occur at synamses that use excitatory glutamate receptor
NMDA receptor
But ions not enter as blocked
If larger amounts released stimulated AMPA receptor
Cause influx sodium ions that throw out Mg ions
Suddenly NMDA receptor becomes active
Ca enter cell & cause changes (more AMPA receptors) = More receptive over time as more receptors
Steps
More neurotransmitter released from pre-synaptic terminal
More receptors available for binding at post-synaptic terminal
Retrograde messengers pass from post- to -pre-synaptic neurone instructing to release more neurotransmitter
Interim Summary
LTP may be feasible mechanism for memo
LTP dependent on host molecular processes mediated by glutamate
Summary
Memo characterised as networks of associations
Hebb expanded on this
Co-activation of diff event elements strengthens connections between
LTP provides potential synaptic mechanism for this
Increased response to high-frequency stimulation potentiates response to weaker stimulation which endures over time
LTP provides general mechanism for understanding how (via learning) memo formed in brain
Core idea memo encoded via experience dependent changes in synaptic strength
LTP provide bio mechanism for idea & appealing properties
Confirm Hebbian logic
Support for synaptic plasticity