You Are Your Memory Your memory stores: Your personal experiences Emotions Preferences/dislikes Motor skills World knowledge Language Fundamentally, you as a person are derived from experiences that have been stored in your nervous system. This is possible only because your brain has developed the capacity to store information.

Figure 1.1 Learning and memory explain the fact that our past experience influences our behavior

Definition “Learning is the process of acquiring new information, while memory refers to the persistence of learning in a state that can be revealed at a later time” (Squire, 1987).

Goal of Neurobiology The goal of neurobiologists is to understand how the brain acquires, stores, and maintains representations of experience in a persistent state that permits the information contained in the representation to be retrieved and influence behavior.

Two Approaches to the Study of Memory: Psychological and Neurobiological Study of memory used to be the sole territory of psychologists. However, today neurobiologists also have weighed in. Psychological Approach: The general goal of psychology is to (a) derive a set of empirical principles that describe how variation in experience influences behavior, and (b) provide a theoretical account that can explain the observed facts.

Ebbinghaus and Memory Hermann Ebbinghaus developed the first scientific methods for assessing the acquisition and retention of a controlled experience. To study “pure memory” required a methodology that could separate what the subject already has learned from what the subject is now being asked to remember. So he invented the nonsense syllable.

Figure 1.2 Ebbinghaus documented the first forgetting curve

Figure 1.3 Single-trace and dual-trace theories of Ebbinghaus’s forgetting curve

Psychologists Only Study Memory at a Single Level of Analysis Psychologists study only the relationship between experience and behavior. This means they do not directly manipulate or measure brain processes.

Neurobiologists Are Motivated by the Belief that Memory Traces Have a Physical Basis in the Brain To understand the physical basis of memory requires a multiple level approach. Not only is the brain manipulated, responses in the brain to experience and drugs are measured. Thus neurobiologists study brain systems, synapses, and molecules, as well as behavior.

Historical Foundations: The Golden Age About 30 years ago Paul Rozin described the last decade of the 19th Century as the “Golden Age of Memory” because during that era many of the basic phenomena and ideas that still occupy researchers emerged. Paul Rozin

Historical Foundations: The Golden Age Théodule Ribot proposed that during disease of the brain, memories disappear in an orderly fashion. The Dissolution of Memory FirstLast

Historical Foundations: The Golden Age Ribot’s Law: Ribot also proposed that old memories are more resistant to disease/disruption than new memories.

Historical Foundations: The Golden Age Serge Korsakoff Described the syndrome produced by alcohol now called Korsakoff’s Syndrome. The syndrome is characterized by what we would now call anterograde amnesia—the inability to acquire new memories. During the late stages there is also retrograde amnesia—the loss of memories acquired before the onset of the disease. He also proposed that amnesia could be due to either storage failure or retrieval failure.

Historical Foundations: The Golden Age William James proposed that memories emerge in stages. An after image is supported by a very short-lasting trace, then replaced by the primary trace that also decays. Secondary memory is viewed as the reservoir of enduring memory trace that with an appropriate retrieval cue can be recalled.

Figure 1.6 William James proposed that memories emerge in stages

Historical Foundations: The Golden Age Santiago Ramón y Cajal The Neuron Doctrine: The idea that the brain is made up of discrete cells called nerve cells, each delimited by an external membrane. The Synaptic Plasticity hypothesis: The idea that the strength of a synaptic connection can be modified by experience.

Historical Foundations: The Golden Age In the Pavlovian conditioning method, two events called the CS and US are presented together. Subsequently, the CS evokes the response called the CR. Psychologists assume that the CS evokes the CR because the CS gets associated with the US. Psychologists and neurobiologists continue to use this method to study associative learning in animals. Ivan P. Pavlov Developed the fundamental methodology for studying associative learning in animals.

Figure 1.8 Pavlovian conditioning is widely used to study learning and memory in animals

Historical Foundations: The Golden Age Edward L. Thorndike Developed the first methodology for studying how we learn about the consequences of our actions. This methodology is called instrumental conditioning. Some people also call it Thorndikian conditioning. The Law of Effect: The correct behavior was learned because the consequences of successful outcome (a satisfying state) strengthened connections between the stimulus (S) and correct response (R) and the consequence of unsuccessful responses (annoying state) weaken the competing and wrong S–R connections.

Figure 1.9 Edward L. Thorndike invented the methodology for studying instrumental learning

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08-05 Atkinson, R.C., and Shiffrin, R.M., Human Memory: A Proposed System and Its Control Processes, in Spence, K.W., and Spence, J.T. (Eds.), The Psychology of Learning and Motivation, Vol. 2. New York: Academic Press, 1968, _pp. 89–195. Adapted by permission of the publisher.

08-07 Baddeley, A., and Hitch, G., Working Memory, in Bower, G.H. (Ed.), The Psychology of Learning and Motivation, Vol. 8. New York, Academic Press, 1974, pp. 47–89. Adapted by permission of the publisher.

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Memory & Brain

mplates/player/mediaP layer.html?action=1&t =1&islist=false&id= &m= h ttp:// plates/player/mediaPla yer.html?action=1&t= 1&islist=false&id= &m= h ttp:// plates/player/mediaPla yer.html?action=1&t= 1&islist=false&id= &m= Henry Gustav Molaison (1926 – 2008)

Patient H.M. “Right now I'm wondering, Have I done or said anything amiss? You see, at this moment everything looks unclear to me, but what happened just before? That's what worries me. It's like waking from a dream; I just don't remember.” “Every day is alone in itself, whatever enjoyment I've had, and whatever sorrow I've had.” -- H.M.

08-13 Fig. 6.1, Corkin et al., “H.M.’s medial temporal lobe lesion: Findings from magnetic resonance imaging,” The Journal of Neuroscience 17: 3964–3979, (1997). Adapted with permission of The Society for Neuroscience.

Neuropsychology patients

Memory Systems in the Brain Medial temporal lobe amnesia Inability to form new explicit memories (anterograde amnesia) Good IQ, good implicit learning Loss of memories from before injury (retrograde amnesia)

Working/Short-term Memory –Can carry on a normal conversation –Normal memory span Intelligence and Language Normal –Note that some of these rely on spared retrograde memory (vocabulary, math rules, etc)

Skill Learning –“motor, perceptual, or cognitive operations or procedures that are typically acquired through an incremental and slow process of repetition. –Mirror reading –Rotary Pursuit –Artificial Grammar Learning –Perceptual Classification –Tower of Hanoi (not reliable!)

Memory Systems in the Brain

Memory activates hippocampus

Memory Systems in the Brain

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Patient EP

Memory Teng & Squire, 1999

Hippocampus & memory But see patients like … Long-term retrograde amnesia… the crucial role of the hippocampus Lisa Cipolotti, Tim Shallice, Dennis Chan, Nick Fox, Rachel Scahill, Gail Harrison, John Stevens, Peter Rudge Neuropsychologia 39 (2001) 151–172 Patient VC shows bilateral hippocampal loss with no involvement of entorhinal cortex or temporal neocortex

Hippocampus & memory Memory for major public events

Hippocampus & memory Memory for famous faces

Hippocampus & memory Autobiographical and semantic memory

Hippocampus & memory Anomalies for standard view 1.Variation in RA duration - 72 hr to 35 years 2. Examples of flat gradients - experimental and clinical 3. RA with no anterograde amnesia (less specificity in RA)

The Chemical Basis of LTP: Antagonizing NMDA receptors block the induction of LTP, not the expression of LTP

Long-Term Depression: The Polar Opposite of Long-Term Potentiation

Review: A Core Signaling Cascade Glutamate is released from the presynaptic or sending neuron. Glutamate binds to both AMPA and NMDA receptors. The cell is depolarized when enough Na + enters the cell through AMPA receptors. The combination of binding glutamate to the NMDA receptor and depolarizing the cell removes the Mg + plug from the NMDA channel. Calcium enters the dendritic spine through the NMDA channel. So what does calcium do? To answer this question, one must understand first and second messengers.

Figure 3.1 First messengers carry information between neurons; second messengers carry the signal into the neuron

Functional Endpoints: A General Framework

The Dynamic Life of AMPA Receptors

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Unilateral cerebellar cortex lesion