PSYC 2: Biological Foundations - Fall 2012 - Professor Claffey

Notes: Cognition 2

Version:
11/18/12 - original version

Memory Classifications

memory classifications

A note on memory classifications
    Definitions developed from observing behavior and trying to classify memories accordingly
        These definitions could sometimes be fuzzy (e.g. semantic versus episodic)
    As we understand more about the brain, can classify according to necessary _______________

_____________ memory
    Examples: Obama is president, PSYC 2 is in Price Center Theater, my 21st birthday was a disaster

    facts (_____________), experiences (_____________), locations
    conscious and explainable (you can be explicit about the memory)

_____________ memory
    Examples: how to tie a shoe lace, the steps to get from your bed to the bathroom, fear of spiders
    skills, routines, emotional memories
    subconscious and not easily explained

An experience might lead to both explicit and implicit memories
    You might be afraid of spiders and be able to explain when you formed this memory
    But the explicit/implicit components of that memory will be handled differently (see below)


Amnesia Patients

These amnesiac patients have damage to ___________________ and problems with _____________ memory

Patient: H.M.

brenda milner
Milner (source)

H.M. had bilateral medial temporal lobe lesions for epilepsy in 1953
Studied by Scoville (surgeon) & Brenda Milner (psychologist) in 1957
    He was a pivotal case study that changed our understanding of memory
Post surgery:
    well-adjusted, sensory & motor intact, high intelligence, short term memory intact
    didn't have memories for events up to 2 years before surgery, but older memories intact
    could NOT form new memories such as address, why he's in the hospital, people he met
Died in 2008, brain donated to and digitized by UCSD's Brain Observatory

h.m. anatomy h.m. anatomy

Intact Learning

h.m. mirror drawing Mirror Drawing

Task: trace a shape with a pencil through a reflection in a mirror
Result:
    HM initially made many errors (similar to normal subjects)
        but improved each day
    HM had no memory of the task or his improvement
Summary:
    HM was capable of learning a skill without being aware of his ability
        (_____________ learning)

Lessons from HM

- There are brain areas dedicated to and necessary for memory (______________________)
- Long term memory is different than short term memory (more functional segregation)
- Ability to change behavior without being aware of it (explicit versus implicit memory)
(Pinel, page 272)

Patient: E.P.

Video on amnesiac E.P. (youtube, 1:34 - 9:30)
Herpes enchephalitis
Charismatic, intelligent, able to reason & problem solve, short term memory (like word lists) intact
Could not permanent store short term memories, remember people, learn address

Patient: Clive Wearing

Video (3 mins)
An accomplished symphony conductor
Herpes enchephalitis
Deficits:
    Couldn't remember own children's name
    Only a few seconds of short term memory
    Constant sensation of having just become conscious for the first time in his life
Intact:
    Still strongly loved his wife (an emotional memory)
    Play piano, conduct symphony, name a few composers, learn habits in his supportive care home

Causes of human amnesia

Damage to hippocampus and surrounding areas
    stroke
    herpes enchephalitis - herpes simplex-1 (cold sores) viral infection of the central nervous system
    Korsakoff's Syndrome - severe alcoholics
    surgery - tumors/epilepsy treatment, bilateral removal of medial temporal lobe are now avoided
    Alzheimer's disease
        changes throughout the brain that also affect hippocampus
        made worse by dementia - patients tend to be confused, so memories are less clear to begin with

Temporal Lobe Anatomy

hippocampus anatomy hippocampus rat
Broad area: medial temporal lobe (MTL)
    Specifically: hippocampus, a critical area within MTL
Hippocampus is / is not present across a full range of mammals

Temporal Gradient

Anterograde vs Retrograde Amnesia

_________________ amnesia - can not form memories AFTER the event

_________________ amnesia - loss of memories formed BEFORE the event

anterograde retrograde memory

Experiment: Famous Faces

Source: Haist et al, 2001
famous faces stimuli
famous faces recall
Task:
    subjects (50+ years old) were healthy and MTL amnesia patients
    subjects were shown pictures of famous faces and asked if they can identify them
    famous faces belonged to people that reached prominence in many different decades
Results:
    healthy patients have comparable memory for faces across all decades
    amnesiac patients are particular bad at remembering celebrities from _____________ decades
    amnesiac patients could/could not remember older memories as well as healthy patients
Summary:
    Amnesia is most likely to affect recently formed memories while older memories are intact


Experiment: Famous Faces - fMRI

data from smith & squire, 2009 Source: Smith & Squire, 2009

Task:
    Same as above but
    All subjects were healthy (no amnesia)
    scanned with fMRI during face recall

Result:
    Hippocampus is more active for _____________ memories

Summary:
    Hippocampus activity matches behavioral responses


Encoding

Experiment: Subsequent Memory

memory encoding brewer fmri
memory encoding
fmri brewer
Source: Brewer et al, 1998

Task:
    Encoding stage:
        subjects view photographs while being scanned in fMRI
    Testing stage:
        after scanning, subjects tested on memory for photographs

Results:
    Photographs that were subsequently remembered during the testing
    stage had produced the greatest activity in the hippocampus during
    the encoding stage

Summary:
    The hippocampus was most active during _____________ of
    photographs that could later be remembered,
    and least active for photographs that were later forgotten

    The brain does not capture all incoming information equally
    Info must be attended to to be encoded and later recalled   



Animal Memory: Fear Conditioning

Experiment: Fear Conditioning

Task:
    Rat/mouse spends time in a small chamber where it receives an aversive foot shock (training)
    Shock is delivered at the same time a tone plays
    Days later, animal is returned to chamber to measure amount of time that the animal freezes (__________)
Results:
    Animal will freeze if returned to identical box (__________ test), even without playing the tone
    Animal will freeze if returned to a differently configured box if the tone is played (__________ test)
Summary:
    Freezing measures fear, which is a form of memory
    Memory is simultaneous formed for the place (context) and the tone
    This basic memory is formed easily/quickly and animal will remember for its life time
    This task can be used to study behavior, but also what is going on in the brain to form this simple memorycontextual fear conditioning setup

Results (below)
    Graph: "Acquisition" (training)
        Animal does freeze initially (BL=baseline),
        but freezes more than 50% of the time after the shocks are delivered
    Graph: "Context Fear"
        Animal will freeze 75% of the first few minutes when it is returned to chamber
        Fear gradually decreases, presumably as animal realizes no more shocks are delivered
    Graph: "Tone Fear"
        Animal doesn't freeze initially (BL=baseline) because the chamber is configured differently
        Once the tone plays (at minute 2), animal suddenly freezes 75% of time
        Fear gradually decreases, presumably as animal realizes no more shocks are delivered

contextual fear conditioning behavior

Experiment: Fear Conditioning - with lesion to hippocampus

Questions:
    Does the context memory depend on the hippocampus?
    Does this dependence on the hippocampus change with time?

Task:
    same as fear conditioning above
    4 different treatments
        some animals have their dorsal hippocampus (DH) lesioned 1 day after training (Recent)
        some animals have a fake lesion procedure (Sham) 1 day after training (Recent)
        some animals have their dorsal hippocampus (DH) lesioned 30 days after training (Remote)
        some animals have a fake lesion procedure (Sham) 30 days after training (Remote)
Result:
    animals given a sham/fake lesion have a good memory for context and freeze about 75%
        regardless of when procedure is performed ("Context Summary" graph, yellow line)
        this condition is done as a control
    if the hippocampus is lesioned when training is Recent, animal loses memory of training
        and doesn't freeze in the context test ("Context Summary" graph, lower right red dot)
    if enough time is given after training, hippocampus lesion doesn't affect content memory
        ("Context Summary", upper left red dot)
    hippocampus lesion does not affect freezing to tone ("Tone Summary" graph)
Summary:
    hippocampus is only necessary for remembering the context immediately after training

        with time, the memory must ___________________ on another part of the brain

    Strong evidence for the ________________________ seen in human amnesia

contextual fear conditioning - hippocampus lesions

Experiment: Fear Conditioning - inhibition of protein synthesis

Question:
    Do you have to make new proteins in order to make (consolidate) a long term memory?

Cell biology background:
    Cells make new proteins by assembling amino acids based on DNA
    Anisomycin is a drug that interferes with this assembly so that cells temporarily can't make any new proteins
Task:
    Same as fear conditioning above
    Prior to training, animals are injected with anisomycin to prevent protein synthesis
Result:
    Animals injected with anisomycin do/do not freeze during the task training
        This is considered short term memory (STM) in the graph below
    Animals injected with anisomycin
do/do not freeze after an extended delay
        This is considered long term memory (LTM) in the graph below
Summary:
    Animals can learn and form a short term memory even if anisomycin is injected.

    However, because they can't make proteins, they can't ________________ a permament memory
    Protein synthesis is necessary for forming long term memories

memory anisomycin consolidation, nader & hardt
Source: Nader & Hardt, Nature Reviews Neuroscience, 2009

Experiment: Fear Conditioning - Reconsolidation

Question:
    Once learned, are memories stable? Can they be unlearned?

Task
    Same as fear conditioning above (no injection of anisomycin yet)
    After training, the memory is reactivated by re-exposing the animal to the context
    Some animals have anisomycin injected prior to re-exposure
    Days later, animals are returned a 3rd time (1st for training, 2nd for re-exposure, 3rd for testing)
Results:
    All animals freeze the same during the re-activation (PR-STM = post reactivation short term memory)
    Animals that had anisomycin during the reactivation had their memory destroyed (PR-LTM)
Summary:
    A reactivated memory requires another round of protein synthesis to __
_______________ it, or the memory will be lost

memory anisomycin reconsolidation, nader & hardt

Source: Nader & Hardt, Nature Reviews Neuroscience, 2009

Memory Consolidation

Molecular Consolidation

ltp this is the process by which memories are formed at the level of the neuron/synapse

also called "Cellular Consolidation"

Strengthening existing synapses (new receptors) and
creating new synapses (new neuron structures)

requires __________________________

Takes place over a time scale of minutes to hours

Systems consolidation

memory consolidation model Theory:
    Hippocampus has _________, adaptive connections to learn quickly
    Cortex has _________ changing connections to maintain knowledge

    The hippocampus __________ the cortex over time if  information is
    useful or frequently encountered

Summary:
memory is initially in hippocampus (or hipp. points to memory)
gradually strengthens in the cortex until hipp. no longer needed

Takes place over a time scale of days to years

Hippocampus & Spatial Memory

Experiment: Morris Water Maze

Task:
    Mice learn to swim around a tub of water to find a hidden platform
    After training, some animals have cortex lesions, some have hippocampus lesions
Results:
    With training, animals learn to swim directly to the location of the hidden platform
    With enough time to consolidate, animals with hippocampus lesions can/can not do the task
Summary/Theory:
    Hippocampus is strongly involved in ____________ memories and always necessary for ____________

water maze setup
water maze lesions

Experiment: Place Cells

place cells nakazawa
Source: Nakazawa... & Tonegawa, 2004

place and grid cells
Source: www.ucl.ac.uk/jefferylab/research
Task:
    Rodents have electrodes implanted to measure from hippocampus
    Rodents are allowed to freely roam in an enclosed area

Results:
    Some neurons in the hippocampus reliably fire whenever
    the animal is in a certain location (__________ cells)

    Other neurons respond in many, grid like locations (_________ cells)

Summary:
    Individual hippocampus neurons "lock on to" or represent specific
    locations

    Together, these neurons make-up a ___________________ of space

Review

Copyright 2012 - Michael Claffey