4 - encoding + early memory formation


MISC.

mnemonics: ex. songlines.

NMDA receptors are coincidence detectors (need glutamate and voltage change to open!!)

increasing AMPA receptor expression in PostSyn membrane strengthens neuron


WHAT IS MEMORY ENCODING?

  • how do we define encoding vs perception vs sensation?

CONCEPT OF ENCODING: HISTORY

  • Deese: integrating or unitizing (chunking) nonsense syllables

  • Melton: perceptual traces and memory traces are the same thing

  • 1980s: Shift to cognitive neuroscience

    • priming, implicit memory, multiple memory systems

    • neuroimaging

What is LOP?

  • Levels of processing (LOP): framework for study of memory with levels of perceptual processing depth

    • Craik and Lockhard

    • memory trace as byproduct of perceptual analysis, influenced by depth of analysis

    • stronger experience (depth, amt of attention, compatibility of info, time spent) → greater retention

      • compatibility: does it fit existing structures (of what you already know)?

What is GAPS?

  • General Abstract Processing System (GAPS): framework for studying episodic memory

    • Tulving (important boi)

    • memory starts with encoding, ends with retrieval.

    • encoding: converting event into an engram (memory trace)

    • ecphory: process of combining information in engram and retrieval cue into ecphoric information

    • ecphoric information: end product of act of cognitive memory

    • encoding is not the same as perception. perception necessary but not enough for memory trace formation


Why have a separate process (encoding and perception)?

  • interruption of encoding

    • can perceive but not recall perception (encoding failure)

    • ex. expt involving high priority item. poor recall of preceding items.

  • remembering events that never happened

    • confabulation. not perceived at all!

  • anterograde amnesia

    • perception intact BUT no memory trace!

  • psychopharmacology of encoding

    • benzodiazepines (depressant) don’t reduce perception of stimuli but have poorer recall


How do we measure encoding in the brain?

  • Sanquist et al.

    • EEG study showed ERPs for words on a list

    • differences between words that were recalled vs not recalled

      • differences reflect encoding!

  • Wagner et al.

    • fMRI study, localized encoding of remembered words vs not remembered words

      • in left prefrontal and temporal cortices

    • damage to prefrontal regions associated with memory deficits but not perceptual!!


Encoding vs consolidation?

Defining encoding:

  • encoding is NOT transduction (environmental energy into neural code)

  • encoding is NOT always sensory encoding (neural sensory code into perceptual code)

  • encoding IS turning perception or experience into memory trace!!


How do neurobiologists understand memory traces? (review)

  • formation of memory trace:

    • starts with behavioural experience → activates weakly connected neurons

    • cellular molecular processes strengthen these neuron connections (LTP, etc)

      • form neural representation of experience → memory trace

      • can reestablish state via retrieval cues

    • neurons that fire together wire together!


Are NMDA receptors critical to memory formation? (Richard Morris)

  • pharmacological approach

  • Setup:

    • cannula implanted into rat brain ventricles, time release pellet

      • pellet contained NMDA receptor antagonist APV

      • rats trained on place-learning version of water escape task

  • Manipulated:

    • infused w APV

    • not infused w APV

  • Results:

    • APV rats impaired learning of hidden platform location

    • during probe trial, control rats selectively* searched platform’s quadrant but APV rats didn’t

  • Takeaway:

    • antagonist inhibits NMDA receptors which impaired memory


NMDA RECEPTOR SUBTYPES

  • NMDA subunits

    • all NMDA receptors have GluN1

    • multiple types of GluN2 subunits

  • NMDA receptor complexes made up of GluN1-GluN2A and GluN1-GluN2B subunits


What occurs with GluN1 deletion in CA1 (hippocampus area)? (Tonegawa)

  • LTP could be induced in dentate gyrus but not CA1

  • impairment performance in hidden platform water escape task

developmental shift in receptor ratios (of GluN2A and GluN2B receptors)

(explore vs exploit!!!!)


What occurs with GluN2B overexpression? (Tsien)

  • “Doogie mouse”

  • GluN1-GluN2B NMDA overexpressed in cortex, hippocampus, amygdala

  • Result:

    • showed enhanced LTP in in-vitro brain slices

    • stable+enhanced memory for contextual fear-conditioning experience

  • increasing expression of GluN2B resulted in improvement of learning and memory!!


Does AMPA receptor trafficking improve memory? (Roberto Malinow)

  • Setup:

    • made GluA1 subunits with distinct electrical conductance from endogenous (in-body) GluA1s

      • labelled receptors w fluorescent protein

    • viral vector system, delivered receptors into neurons of basolateral amygdala

  • Manipulation:

    • tested for fear of tone w shock

    • tested for fear of tone without shock

  • Results:

    • paired condition showed fear to tone

    • brain slices showed fear conditioning increased GluA1 AMPA receptors into dendritic spines


Can dummy AMPA receptors impair memory? (Robert Malinow)

follow up experiment

  • Setup:

    • modified nonfunctional GluA1 receptors, injected into lateral amygdala

      • those receptors compete w endogenous functional GluA1 receptors going to spines

  • Manipulated:

    • injected

    • not injected

  • Results:

    • injected rats had impaired fear conditioning to tone + shock

    • slices from animals with modified receptor couldn’t sustain LTP in lateral amygdala


Can we enhance learning?

  • ampakines: class of drugs designed to improve cognition (neurotropics)

  • Glutamate binds to AMPA receptor. conductance channel opens (short time)

    • + ions enter, depolarization

  • Ampakine only. nothing happens

  • Ampakines and glutamate binds to AMPA receptor. conductance channel opens (longer time)

    • more + ions enter, stronger synaptic response.

  • POSITIVE ALLOSTERIC MODULATION. ampakines enhance rate of auditory fear conditioning (learning)


NMDA and AMPA: role in acquisition and retrieval?

  • Setup:

    • can rats learn and remember location of flavoured food pellets?

  • Manipulated:

    • 2 antagonists used

      • APV (blocked NMDA)

      • CNQX (blocks AMPA)

  • Results:

    • BOTH antagonists: interference w establishing memory

    • ONLY CNQX, affecting AMPA: interfered with retrieval of memory

    • ONLY APV, affecting NMDA: could retrieve the memory

  • Implications:

    • NMDA are needed for acquisition (learning) but Not retrieval (memory)

    • AMPA are needed for BOTH acquisition and retrieval


What is the role of CaMKII in memory?

  • Setup:

    • use CaMKII-deficient mice (CaMKII KO)

    • control group

  • Results:

    • CAMKII KO mice learned to swim to visible platform but couldn’t learn hidden platform

    • Probe trial: control group selectively searched target quadrant, CAMKII KO mice didn’t


How to use the radial maze to study working and reference memory?

  • Setup:

    • rat in middle of maze

    • trial starts at centre of maze, ends when rat gets all 4 rewards.

      • same 4 arms have the rewards each time

  • two types of errors

    • working memory (enters previously sampled arm)

    • reference memory (enters arm never baited)

  • Results:

    • GluA1 KO mice learn + remember Reference memory part, BUT working memory impaired.

  • Implications:

    • reference memory: learning which arms are never baited

    • working memory: remembering which arms you’ve already visited

    • GluA1 receptors are essential for working memory


DUE before the midterm (friday before)

outline taxonomy of mnemonic devices (6 types)

  • (different modalities??)

  • cultural application?

describe my mnemonic!! what category it falls under