PSYC 2: Biological Foundations - Fall 2012 - Professor Claffey

Notes: Cognition 2

Version:
11/18/12 - original version

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

Patient: H.M.

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

Intact Learning

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

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

Temporal Gradient

Anterograde vs Retrograde Amnesia

_________________ amnesia - can not form memories AFTER the event

_________________ amnesia - loss of memories formed BEFORE the event

Experiment: Famous Faces

Source: Haist et al, 2001

Experiment: Famous Faces - fMRI

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

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 memory

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

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

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

Source: Nader & Hardt, Nature Reviews Neuroscience, 2009

Memory Consolidation

Molecular Consolidation

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

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 ____________

Experiment: Place Cells

Source: Nakazawa... & Tonegawa, 2004 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

• Explicit memories depend on the medial temporal lobe (MTL), specifically the hippocampus
• The importance of hippocampus was revealed by human amnesiacs with a deficit in creating new memories
• Contextual fear condition is a popular memory experiment because it is easy to train, depends on a natural behavior, is long lasting and involves the hippocampus
• Molecular consolidation - forming new memories requires making new proteins to change synaptic strength
• Systems consolidation - memories are initially dependent on the hippocampus but transition over time, likely to the cortex
• Reconsolidation - memories can become vulnerable once they are reactivated
  
• The hippocampus is heavily involved in spatial tasks:
• the hippocampus is always required for successful navigation in the water maze task
• the hippocampus has place cells - neurons that reliably fire when an animal is in a specific location