8 Learning and Memory 1 I remember, therefore I am – Chung-Chuan Lo

Main stages in the memory processing – Encoding: Acquisition and consolidation – Storage – Retrieval 2

3

The Atkinson and Shiffrin modal model of memory (1968) 4

Short-term memory capacity George Miller in 1950s The average capacity of short-term memory is seven The capacity is independent of the content of the items When digits are used for testing, this feature is referred to as digit span Information is encoded in short-term memory as chunks, not bits 5

Dissociation between short-term and long-term memory Patient H. M. -- Normal short-term memory; Deficit in long-term memory Temporal lobes removed (1953) Patient E. E. – Normal long-term memory; Deficit in short-term memory Tumor in left angular gyrus (1999) 6

Working memory Short-term memory + the ability to manipulate and transform the information and use it in high level behaviors The contents of working memory could either originate from sensory input or could be retrieved from long-term memory. 7

Lesion leads to deficits in visuospatial short-term memory Lesion leads to reduced auditory-verbal memory spans 8

9

Classification of long-term memory I Declarative / explicit memory Accessible to consciousness and can be readily communicated or declared to others. Semantic memory Episodic memory Autobiographical memory Semantic memory General knowledge / factual information Independent of context and personal relevance May stored in the same brain regions with the episodic memory Episodic memory Mental representation about 'what', 'where' and 'when' about an event Of all human capabilities, the one central to our development of a unique sense of personal identity is episodic memory. In the 1970s, psychologist Endel Tulving introduced the distinction between episodic and semantic memory But, are these two memory types supported by different neural systems? 10

Nondeclarative / implicit memory Skill and habit (procedural memory) Priming and perceptual memory Classical conditioning Nonassociative learning Classification of long-term memory II 11

Classical Conditioning Classical (Pavlovian) conditioning Instrumental (operant) conditioning Ivan Petrovich Pavlov ( ): Nobel Prize in Physiology or Medicine in

Amnesia Types Anterograde amnesia: a loss of the ability to create new memories after the event that caused amnesia Retrograde amnesia: a loss of access to events that occurred, or information that was learned, before the onset of amnesia (caused by injury or a disease) Causes Neurological amnesia: caused by injury or disease. Characterized by severe anterograde amnesia and some retrograde amnesia Funcational amnesia: caused by emotional trauma. Characterized by profound and transient (in some cases) retrograde amnesia but little anterograde amnesia 13

14

He performed poorly on memory for short stories, word lists, pictures, and a wide range of other materials. Remarkably, it was unclear that he even remembered that he had undergone brain surgery The severity of H.M.’s amnesia was shocking—he showed almost no capacity for new learning. Also, the fact that the brain damage was known to be confined to a particular region (the medial temporal lobes) added to the intrigue. H. M. and his amnesia I HM – The man who couldn’t remember

1.Formal testing identified that cognitive abilities other than memory were intact → Memory could be separated from perception and intelligence. 2.H.M. could hold on to small amounts of information as long as he was actively rehearsing the information. → The ability to maintain working memory was distinct from the ability to make a lasting record in the brain. 3.H.M.’s childhood memories were relatively intact. → Although the medial temporal lobes might be important for forming new memories, this region was unlikely to be the final storage site for memory. 4.Fourth, H.M. had an intact ability to acquire new motor skill learning (Milner, 1962). → Memory is a dissociable cognitive capacity and that day to day memory was supported by brain structures that differed from those that supported the acquisition of motor skills. H. M. and his amnesia II H.M.’s case ushered in the modern era of research on memory systems came from the four aspects of his mental capacity that remained intact. 16

17

18

19

20

Hippocampus – Animal studies I Damage to the hippocampus and parahippocampal region produces anterograde amnesia → The hippocampal memory system ordinarily supports the declarative memory for both episodic semantic memory. Amnesia resulting from damage restricted to the hippocampus and parahippocampal region is highly selective in four important ways 1.Perceptual, motor, and intellectual functions are intact. 2.Memory acquired long before the onset of amnesia is typically intact. 3.The capacity for immediate memory is typically intact in amnesic patients, and, just as in the case for healthy individuals. 4.The various forms of memory that are supported by brain systems outside the hippocampal memory system are intact in amnesic patients. 21

Hippocampus – Animal studies II Delayed nonmatching to sample task When the delay is only a few seconds, monkeys with experimental lesions that include the same medial temporal lobe structures damaged in H.M. (including the hippocampus and adjacent cortices) performed as well as normal monkeys (Mishkin, 1978). As the delay was increased, the monkeys became progressively more impaired. Using this animal model, investigators were able to identify the structures of the medial temporal lobe critical to supporting declarative memory Damage limited to the hippocampus, or to its major connections through the fornix, produces only a modest impairment. In contrast, damage that includes the adjacent cortices produces severe amnesia. 22

23

Many studies in rats have demonstrated that damage to the hippocampus results in deficits in a variety of spatial learning and memory tasks. Hippocampus – Spatial memory Rats with hippocampal damage are severely impaired in the water maze task. 24

Amygdala – the contribution to emotion The amygdala contributes to emotion in several ways, including mediating emotional influences on attention and perception and regulating emotional responses. 1. The amygdala supports the acquisition of emotional dispositions toward stimuli. This kind of memory includes preferences and aversions. 2.The amygdala mediates the influence of emotion on the consolidation of memory in other memory systems 25

Amygdala – Acquiring emotional dispositions to stimuli I Fear conditioning experiment: Conditioned fear elicited by the tone is assessed by measuring autonomic responses, such as changes in arterial pressure, and motor responses, such as stereotypic crouching or freezing behavior. Rats with lesions in the BLA (basolateral amygdala complex) show dramatically reduced conditioned fear responses to the tone in measures of both autonomic and motor responses but still show normal unconditioned fear responses to the shock itself. 26

Associative Learning: Formation of associations among stimuli and/or responses. Subdivided into classical conditioning and instrumental (operant) conditioning. Nonassociative Learning: Three examples of nonassociative learning have received the most experimental attention: habituation, dishabituation, and sensitization Associative Learning & Nonassociative learning 27

Vertebrate studies: Long-term potentiation Long-term potentiation (LTP): Defined as a persistent increase in synaptic strength Typically measured by the amplitude of the EPSP (excitatory post-synaptic potential) in a follower neuron First demonstarted in 1973 by Timothy Bliss and Terje Lomo demonstrated LTP in the hippocampus of an anesthetized rabbit. Now known to occur in the cerebellum, neocortical regions, subcortical regions such as the amygdala, mammalian peripheral nervous system, the arthropod neuromuscular junction, and the Aplysia sensorimotor synapse. No universal mechanism exists for inducing LTP.

LTP at the CA3–CA1 synapse in the hippocampus Two time domains: An enhancement that persists for about 90 min → early LTP (E-LTP). An enhancement that persists for periods of time greater than about 90 min → late LTP (L-LTP)

Cooperativity, Associativity & Input specificity The CA3-CA1 LTP are classic with the following properties: Cooperativity Associativity Input specificity Associativity Cooperativity & specificity

When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased Donald O. Hebb ( ) Neurons that fire together wire together. Hebbian theory: Hebbian learning

Could the classical properties of LTP all be consequences of synapses that obey a Hebbian rule? Hebbian rule & LTP Possibly so if a critical amount of postsynaptic depolarization were a necessary condition for inducing LTP in active synapses. Cooperativity → enough input fibers need to be stimulated to produce the critical amount of postsynaptic depolarization. Associativity → strong input caused sufficient depolarization of the postsynaptic membrane during the presynaptic activity in the weak input. Input specificity → LTP was induced only in those inputs to a neuron that were active at the same time that the cell was sufficiently depolarized by the strong input to that neuron.

Mechanisms of Long-Term Potentiation Induction of LTP depends on an increase in the intracellular concentration of calcium ions ([Ca 2+ ] i ) in some key compartment of pre- and/or postsynaptic cells (Bliss and Collingridge, 1993; Johnston et al., 1992; Nicoll and Malenka, 1995). Two major pathways that have been studied extensively Calcium influx through ionotropic GluRs, especially NMDA receptors Calcium influx through voltage-gated calcium channels (VGCCs).

The NMDAR has two properties that immediately suggest the nature of its role in LTP induction at Hebbian synapses: NMDA receptor and LTP 1.NMDARs are permeable to Ca The channel permeability is a function of both pre- and postsynaptic factors. → Channel opening requires the neurotransmitter glutamate (presynaptic condition) → Sufficient depolarization to remove the magnesium block (post synaptic condition)