Chapter 11: Learning, Memory, and Amnesia

Memory consolidation

-Fact that concussions preferentially disrupt recent memories suggests that storage of older memories has been strengthened/consolidated -Gradients of retrograde amnesia after concusssion provide evidence for this

Explicit vs. Implicit memories

-Explicit = declarative memories, conscious long-term memroies -Implicit = long term memories that are expressed by improved performance without conscious recall or recognition

Global Cerebral Ischemia and delayed nonmatching-to-smaple test

- In both monkeys and rats, global cerebral ischemia leads to a loss of CA1 hippocampal pyramidal cells and severe deficits in performance on the delayed nonmatching-to-sample test. -The relation between ischemia-produced hippocampal damage and object-recognition deficits in humans, monkeys, and rats seems to provide strong support for the theory that the hippocampus plays a key role in object-recognition memory.

Transient Global Amnesia

-A sudden onset severe anterograde amnesia and moderate retrograde amnesia for explicit episodic memory that is tranisent (4-6 hours) -Sudden onset in absence of any obvious cause -Strongest evidence that selective hippocampal damage can cause medial temporal lobe amnesia -Investigators have identified abnormalities to the CA1 subfield of the hippocampus -The time course of these abnormalities - not usually apparent for several hours after the beginning of the attack and have usually cleared up 10 days later - are suggestive of stroke-induced damage

What type of explicit long term memory do people with medial temporal lobe amnesia have?

-Episodic memories -Have difficutly remembering specific events from their lives, even though their memory for general information is often normal -Can't remember having lunch, going to a movie, chatting with a friend, but can often remember what their friends are like, world events, and sorts of things learned at school

Concept cells

-Also known as Jennifer Aniston neurons -Respond to ideas/concepts rather than to particulars -For example, a Halle Berry neuron responded to all photos of the actress (even when she was dressed in her Cat Woman costume), to her printed name, and to the sound of her name. -In one case, a neuron that invariably responded to the Sidney Opera House responded to photos of the Bahai temple in India. When questioned about it later, the patient said she thought the Bahai temple photos were photos of the Sidney Opera House. -Similarly, when participants are given ambiguous human faces (faces that are the average of two well-known faces, such as Whoopi Goldberg and Bob Marley), these concept cells respond only when the viewer perceives the concept to which the cells are attuned to—for example, only when the viewer perceives Whoopi Goldberg, as opposed to Bob Marley -Interestingly, when Jennifer Aniston neurons (concept cells) have been found to respond to more than one concept, there is usually an obvious relation between them. For example, on a second day of testing, it was discovered that the first Jennifer Aniston cell also responded to Lisa Kudrow, Jennifer Aniston's costar in the television series Friends. Another neuron responded to both Luke Skywalker and Yoda, both characters from the movie series Star Wars. Accordingly, it has been suggested that images trigger activity in circuits of concept cells in the medial temporal lobes

Alzheimer's disease amnesia

-Alzheimer's disease is a major cause of amnesia, most common form of dementia with 3 defining characteristics: neurofibrillary tangles, amyloid plaques, neuron loss -First sign of Alzheimer's disease is often a mild deterioration of memory, but the disorder is progressive and eventually the dementia develops and becomes so severe that the patient can't even do simple activities like eating, speaking, recognizing a spouse, bladder control -A terminal disease

Medial temporal lobe amnesia

-Amnesia associated with bilateral damage to the medial temporal lobes; major features are anterograde and retrograde amnesia for explicit memories, with preserved intellectual functioning -Neuropsychological patients with a profile of mnemonic deficits similar to those of H.M., with preserved intellectual deficits, similar to those of H.M.

Posttraumatic Amnesia (PTA)

-Amnesia following an nonpenetrating blow to the head -Concussion (temporary disturbance of consciousness produced by a nonpenetrating head injury) --> most common cause of amnesia

Medial Diencephalic Amnesia

-Amnesia, such as Korsakoff amnesia, associated with damage to the medial diencephalon -N.A: patient with this had medial diencephalic damage, including damage to the mediodorsal nuclei and mamillary bodies

Amygdala and memories

-Amygdala is thought to play a special role in memory for the emotional significance of experiences -Rats with amygdalar lesions, unlike intact rats, do not respond with fear to a neutral stimulus that has previously been followed by electric foot shock -A case of a neuropsychological patient with bilateral damage to the amygdala couldn't acquire conditioned autonomic startle responses to various visual or auditory stimuli but had good explicit memory for the training -There is little evidence that the amygdala stores memories; it appears to be involved in strengthening emotionally significant memories stored in other structures -Amygdala may be the reason why emotion-provoking events are remembered better than neutral events

Entorhinal cortex

-Area of medial temporal cortex that is a major source of neural signals to the hippocampus -A possible answer to the question of how hippocampal place cells obtain their spatial information came from the discovery of grid cells in the entorhinal cortex -Other types of neurons in the entorhinal cortex are associated with spatial location: For example, head-direction cells are tuned to the direction of head orientation, and border cells fire when the subject is near the borders of its immediate environment

Inferotemporal cortex and memory

-Areas of the brain that are active during retention of an experience tend to be the same ones active during the original experience -Inferotemporal cortex = cortex of the inferior temporal lobe, in which is located an area of secondary visual cortex -Has complex visual functions -There is a view that the inferior temporal cortex, in concert with adjacent perirhinal cortex, plays an important role in storing memories of visual input -Naya, Yoshida, and Miyashita (2001) recorded the responses of neurons in inferotemporal cortex and perirhinal cortex while monkeys learned the relation between the two items in pairs of visual images. -When a pair was presented, responses were first recorded in inferotemporal neurons and then in perirhinal neurons; however, when the monkeys were required to recall that pair, activity was recorded in perirhinal neurons before inferotemporal neurons. Naya and colleagues concluded that this reversed pattern of activity reflected the retrieval of visual memories from inferotemporal cortex.

Hebb's postulate for learning

-Assumption that co-occurence is a physiological necessity for learning and memory -Co-occurence of firing in presynaptic and postsynaptic cells = critical factor of LTP

Usual method for making hippocampal lesions in monkeys and rats

-Because of the size and location of the hippocampus, almost all studies of hippocampal lesions in monkeys have involved aspiration (suction) of large portions of medial temporal cortex in addition to the hippocampus -In rats, the extraneous damage with aspiration lesions of hippocampus is typically limited to only a small area of parietal neocortex -Furthermore, the rat hippocampus is small enough that it can be lesioned electrolytically or with intracerebral neurotoxin injections—methods that produce less extraneous damage

Role of hippocampus in spatial memories in humans

-Effects oc hippocampal damage on performance of spatial memory tasks in humans and other primates are less consistent -Spatial memory in human + monkeys is often tested while they remain stationary and make judgements of location on computer screen whereas spatial memory in rats, mice, birds is studied as they navigate through test environments

Grid cells

-Entorhinal neurons that each have an extensive array of evenly spaced place fields, producing a pattern reminiscent of graph paper -The distance between the evenly spaced place fields is flexible; in experimental animals kept in smaller or oddly shaped environments, the fields are closer together or sheared, respectively - The even spacing of the place fields in the grid cells could enable spatial computations in hippocampal place cells. Grid cells have also been identified in other species including human patients

Medial temporal cortex components

-Entorhinal, perirhinal, and parahippocampal cortices

Mirror-Drawing Test

-First indication that H.M's anterograde amnesia didn't involve ALL long-term memories came from this test -H.M's task: draw a line within the boundaries of a star-shaped target by watching his hand in a mirror - H.M was asked to rtace the star 10 times on each of 3 consecutive days, and the number of times he went outside the boundaries on each trial was recorded -His performance improved over the 3 days, which indicates retention of the task -Despite his improved performance, H.M couldn't recall ever having completed the task before -Suggested his sensorimotor tasks were one exception to his inability to form long-term memories

Food-catching birds and hippocampus function

-Food-catching birds must have remarkable spatial memories because in order to survive, they must remember the locations of hundreds of food caches scattered around their territories -In one study, it was found that food-caching species tended to have larger hippocampuses than related nonfood-caching species

Classic study of Squire, Slate,r and Chace on ECS-produced retrograde amnesia

-Found long gradient -Measured memory of a group of patients treated with ECS for television shows that had played for only 1 seasons in different years prior to their ECS -They tested each patient twice on different forms of the test: once before they received a series of 5 electroconvulsive shocks, and once after -The difference between the before- and after-scores served as an estimate of memory loss for the events of each year -The shocks disrupted the retention of TV shows that had played in the 3 years prior to treatment but not those that had played earlier

The case of R.B and transient global amnesia

-Global cerebral ischemia = Interruption of blood supply to a patient's entire brain -Often suffer from medial temporal lobe amnesia -R.B suffered ischemic brain damage that left him amnesic, not as sever as HM but similar -Obvious brain damage was restricted largely to the pyramidal cell layer (one of the major layers of cell bodies in the hippocampus) of just one part of the hippocampus - CA1 subfield -R.B's case suggested that hippocampal damage by itself can produce medial temporal lobe amnesia, but in cases of cerebral ischemia it's difficult to rule out possiblity of subtle damage to other areas of the brain

Incomplete-Pictures Test

-H.M could also form new long-term memories for the incomplete-pictures test -A test of memory measuring the improved ability to identify fragmented figures that have been previously observed -Nonsensorimotor test of memory, employs 5 sets of fragmented drawings and each set contains drawings of the same 20 objects, but sets differ in degree of completeness -Set 1: most fragmented drawings, set 5 contains complete drawings -Subject is asked to identify the 20 objects from the most fragmented set (set1) then those objects that go unrecognized are presented in their set 2 version, and so on, until all 20 items have been identified -Improved after 1 hour of the initial test --> although he couldn't remember previously performing the task

Block-Tapping Memory-Span test

-H.M had global amnesia - amnesia for information presented in all sensory modalities -Milner demonstrated that H.M's amnesia was not restricted to verbal material by assessing his performance on the +1 version of the block-tapping-memory-span test -An array of 9 blocks was spread out on a board in front of H.M., and he was asked to watch the neuropsychologist touch a sequence of them and then to repeat the same sequence of touches -H.M had a block-tapping span of 5 blocks, which is in the normal range; but he couldn't learn to correctly touch a sequence of 6 blocks, even when the same sequence was repeated 12 times

Digist Span +1 Test

-H.M's inability to form certain long-term memory was illustrated with this test -Tests verbal long-term memory -Asked to repeat 5 digits that were read to him at 1-second intervals -He repeated the sequence correctly -On the next trial, same 5 digits were presented in same sequence with 1 new digit added onto it: this same 6 digit sequence was presented a few times until he got it right, then another digit was added onto it, and so on -After 25 trials, H.M couldn't manage to repeat the 8-digit sequence -Most people can correctly repeat about 15 digits afte 25 trials of the digit span +1 test

Pavlovian Conditioning

-H.M. learned an eye-blink Pavlovian conditioning task, even though at a slower rate -A tone was sounded just before a puff of air was adminstered to his eyes, and these trials were repeated until the tone alone elicited an eye blink -2 years later, H.M. retained the conditioned response almost perfectly, even though he had no conscious recollection of the training

Hebb's hypothesis on learning and memory

-Hebb's hypothesis = enduring facilitations of synaptic transmission are the neural bases of learning and memory

Classic theory of memory consolidation

-Hebb's theory -Argued that memories of experiences are stored in the short term by neural activity reverberating in closed circuits, and these patterns of neural activities are suscpetible to disruption by things such as a blow to the head but eventually, they induce structural changes in the involved synapses, which provide stable long-term storage -Electroconvulsive shock seemed to provide a controlled method of studying memory consolidation -Electroconvulsive shock (ECS): is an intense, brief, diffuse, seizure-inducing current that is adminstered to the brain through large electrodes attached to the scalp -Rationale for using ECS for memory consolidation studies was that by disrupting neural activity, it would erase from storage only those memories that had not yet been converted to structural synaptic changes; the length of the period of retrograde amnesia produced by an ECS would provide an estimate of time needed for memory consolidation -Hebb's theory implies that memory consolidation is relatively brief, a few seconds or minutes, about as long as specific patterns of reverbetory neural activity could conveivably maintain a memory but many studies have found evidence for much LONGER gradients

How perspective of hippocampus in memory has changed

-Initially thought to be site of temporary storage for ALL newly formed memories -However, it was soon discovered that the structures of the medial temporal lobes have a more specific function—they appear to play a major role only in explicit episodic memories. -It was discovered that the role of the hippocampus in one's object-recognition memory is minor compared to the contribution of adjacent medial temporal cortex. -Today, the hippocampus is considered to be just one of several brain structures that play important roles in memory.

Current View of Memory Consolidation

-It continues for a very long time, if not indefinitely -The evidence indicates that lasting memories become more and more resistant to disruption throughout a person's life -Each time a memory is activated, it is updated and linked to additional memories and these additional links increase the memories resistance to disruption by cerebral trauma such as concussion or ECS

Korsakoff's Syndrome Amnesia

-Korsakoff's syndrome is a disorder of memory common in people who have consumed large amounts of alcohol; largely attributable to brain damage associated with thiamine deficiency that often accompanies heavy alcohol consumption -Characterized by variety of sensory + motor problems, confusion, personality changes, and risk of death from liver, GI, heart disorders -Lesions to medial diencephalon (medial thalamus + hypothalamus) and diffuse damage to several other brain structures including neorcortex, hippocampus, and cerebellum common -Amnesia of Korsakoff's syndrome is similar to medial temporal lobe amnesia in some respects -During early stages of the disorder, anterograde amnesia for explicit episodic memories is most prominent symptom but as the disorder progresses, retrograde amnesia, which can eventually extend back into childhood, also develops -Deficits in implicit memory depend on particular test used, but in general are less severe than in explicit memory -The gradual, insidious onset and progressive development of Korsakoff's syndrome complicate the study of resulting retrograde amnesia -Brain damage associated with Korsakoff's snydome is DIFFUSE

Long-term depression (LTD) and metaplasticity

-LTD occurs in response to prolonged low-frequency stimulation of presynaptic neurons

Contributions to Alzheimer's amnesia

-Level of Acetylcholine is greatly reduced in brains of patients with Alzheimer's -This reduction results from degeneration of the basal forebrain (midline area located just above the hypothalamus), which is the brain's main source of ACh -This finding, coupled with the finding that strokes in the basal forebrain area can cause amnesia, led to the view that ACh depletion = cause of Alzheimer's amnesia -ACh depletion resulting from damage to basal forebrain isn't the only factor -Brain damage associated with Alzheimer's is very diffuse, involving many areas including the medial temporal lobes and the prefrontal cortex, which both play major roles in memory

Lobectomy vs. Lobotomy

-Lobectomy: operation in which a lobe, or major part of one, is removed from the brain -Lobotomy: Operation in which a lobe, or major part of one is seperated from the rest of the brain by a large cut but not removed

Anterograde amnesia

-Loss of memory for events occurring after the amnesia-inducing brain injury

Retrograde amnesia

-Loss of memory for events/information learned before the amnesia-inducing brain injury

H.M

-Man had medial portions of his temporal lobes removed for treatment of epilepsy -Had a bilateral medial temporal lobectomy -This included the hippocampus, amygdala, and adjacent cortex

Place cells

-Many hippocampal neurons are place cells -Place cells are neurons that respond only when they subject is in specific locations (i.e., in the PLACE FIELDS of the neurons) -When a rat is first placed in an unfamiliar test environment, none of its hippocampal neurons have a place field in that environment, as the rat familiarizes itself with the environment, many hippocampal neurons acquire a place field in it - each fires only when the rat is in a particular part of the test environment -Each place cell has a place field in a different part of the environment -They have been identified in many species, including humans

Long-term memory

-Memory for experiences that endures after the experiences are no longer the focus of attention

To what extent are the object-recognition deficits following bilateral medial temporal lobectomy a consequence of hippocampal damage?

-Most research found that bilateral surgical removal of the medial temporal cortex consistently produced severe and permanent deficits in performance on the delayed nonmatching-to-sample test and other object recognition test -In contrast, bilateral surgical removal of the hippocampus produces only modest deficits, and bilateral destruction of the amygdala produces none. -Lesions of the medial temporal cortex, but not of the hippocampus and amygdala combined, produced severe deficits in performance of the delayed nonmatching-to-sample test in rats.

Jennifer Aniston Neurons

-Neurons fired in response to images of actress Jennifer Aniston but not to 80 other images -Other medial temporal lobe neurons were discovered that responses to other indiviudals familiar to the patients, or to known objects, but because the first neuron responded to Jennifer Aniston, they are called Jennifer Aniston neurons -Neurons that respond to ideas or concepts rather than to particulars -Highly selective -Each neuron respons to only a small number of test objects or individuals - often only one could be found -Responses are highly invariant: if a neuron responded to a particular object on test 1, it repsponded to that object on ALL subsequent tests -Jennifer Aniston cells of hippocampus were even more selective and more invariant than those of other medial temporal lobe structures

Engram cells

-Neurons that maintain an engram

Why is hard to sport episodic memory deficits?

-Neuropsychologists usually have no way of knowing the true events of a patient's life -Patients become very effective at providing semantic answers to episodic questions

Optogenetics

-Neuroscientists insert an opsin gene into particular neurons, after which they can then use light to either hyperpolarize or depolarize those neurons -This tool has been used extensively in studies of learning + memory in mice

What did lesioning particular structures in search of the engram tell us?

-No brain structure has shown that damage to it eliminates all memories of the type its thought to store 1) Memories are stored diffusely in the brain and can survive destruction of any single structure 2) Memories become more resistant to disruption over time

Long-term potentiation

-The enduring facilitation of synaptic transmission that occurs following activation of synapses by high-intensity, high-frequency stimulation of presynaptic neurons -Most frequently studied on roden hippocampus: 3 synapses at which LTP is most commonly studied: dentate granule cell synapse, CA3 pyramidal cell synapse, CA1 pyramidal cell synapse

Nootropics/smart drugs

-Nootropics or smart drugs are substances (drugs, supplements, herbal extracts, etc.) that are thought to improve memory. -The shelves of health food stores are full of them, and even more are available on the Internet. Perhaps you have heard of, or even tried, some of them: ginkgo biloba extracts, ginseng extracts, multivitamins, glucose, cholinergic agonists, Piracetam, antioxidants, phospholipids, stimulants (e.g., amphetamine, methylphenidate), and many more. -Those offering nootropics for sale claim that scientific evidence has proven that these substances improve the memories of healthy children and adults and block the adverse effects of aging on memory. -Although nootropics are often marketed to healthy adults, most research has been done on either nonhumans or humans with memory difficulties (i.e., the elderly). -The relevant research with humans tends to be of low quality, with few participants and poor controls. -For each purported nootropic, there are typically a few positive findings on which the vendors focus; however, these findings are often difficult to replicate or represent very small effect sizes -In short, no purported nootropic has been convincingly shown to have memory-enhancing effects.

The case of R.M was ironic because

-One of the few things that he could remember during his postconcussion confusion was the case of H.M.

Predementia patients with Alzheimer's

-Patients with Alzheimer's who have yet to develop dementia -Memory defecits of these patients are more general than those associated with medial temporal lobe damage, medial diencephalic damage, or Korsakoff's syndrome -In addition to major anterograde and retrograde deficits in tests of explicit memory, predementia patients with Alzheimer's often display deficits in short term memory and in some implicit memory: implicit memory for verbal and perceptual material is often deficient, but implicit memory for sensorimotor learning is not

Prefrontal cortex and memories

-Patients with damage to the prefrontal cortex (area of frontal cortex anterior to motor cortex) are not grossly amnesic; often display no defecits at all on conventional tests of memory -This lack of reliable memory deficits in patients with prefrontal damage may in part result from the fact that different parts of the prefrontal cortex play different roles in memory, and that patients with damage to different areas of prefrontal cortex are often combined for analysis. -Two episodic memory abilities are often lost by patients with larger prefrontal lesions -Patients with large prefrontal lesions often display both anterograde and retrograde deficits in memory for the temporal order of events, even when they can remember the events themselves. -They also display deficits in working memory (the ability to maintain relevant memories while a task is being completed) -As a result of these two deficits, patients with prefrontal cortex damage often have difficulty performing tasks that involve a series of responses -The prefrontal cortex is a large structure that is composed of many anatomically distinct areas that have different connections and, presumably, different functions. -Functional brain-imaging studies are finding that specific complex patterns of prefrontal activity are associated with various memory functions. Some regions of prefrontal cortex seem to perform fundamental cognitive processes (e.g., attention and task management) during working memory tasks, and other regions of prefrontal cortex participate in other memory processes

What is the point of having 2 parallel memory system? Explicit + Implicit?

-Presumably, the IMPLICIT system was the first to evolve because it is more simple (doesn't involve consciousness) -2 experiments: one with patients with amnesia and one with amnesic monkeys with medial temporal lobe lesions suggest that this gives us "flexibility" -In both experiments, subjects with amnesia learned an implicit learning task as well as control subjects did; however, if they were asked to use their implicit knowledge in a different way or in a different context, they failed miserably -Evolution of explicit systems = flexible use of information

Hippocampus role in other types of memory (other than spatial)

-Recently, the hippocampus has been implicated in several forms of memory other than spatial memory. For example, certain cells in the hippocampus have recently been shown to code for the temporal aspects of an experience— so-called "time cells" - Moreover, the hippocampus has been shown to play a role in learning about social organization ("social space") in humans and in mice -Cells in the hippocampus and its surrounding structures have been shown to play a role in the coding of concepts.

Metaplasticity

-Refers to the fact that LTP and/or LTD induction can be modulated by prior synaptic activity -Presumably, a full understanding of LTP and its role in memory will require an understanding of LTD and metaplasticity. And we still don't know what role glial cells play in LTP

Rafdial Arm Maze

-Several arms radiate from a central starting chamber, and the same few arms are baited with food each day -Intact rats readily learn to visit only those arms that contain food and do not visit the same arm more than once each day -The ability to visit only the baited arms of the radial arm maze is a measure of reference memory (memory for the general principles and skills that are required to perform a task) -Ability to refrain from visiting an arm more than once in a given day is a measure of working memory (temporary memory that is necessary for the successful performance of a task on which one is currently working on) -Rats with hippocampal lesions display major deficits on both reference and working memory measures of this test

Identification of engram cells via optogenetics

-The identification of an engram cell via optogenetics is typically a two-stage process. 1) The tagging stage, the neurons that are active during the learning task are induced to express opsins while an animal engages in a particular learning task. 2) In the second stage, the manipulate stage, the previously active neurons are now either inhibited or excited by using light to influence the activity of the opsin-tagged neurons -In essence, researchers are now able to observe, suppress, or activate engram cells in different parts of the nervous system. -For example, researchers have been able to reverse depressive-like behavior in mice by optogenetically reactivating hippocampal dentate granule cells that had previously been active during the encoding of a positive experience -Moreover, researchers have shown that in transgenic mouse models of Alzheimer's disease, activating engram cells leads to the retrieval of memories that are otherwise inaccessible—suggesting that the memory deficits of Alzheimer's disease are retrieval deficits rather than encoding deficits

Monkey Version of the Delayed Nonmatching-to-Sample Test

-Showed that monkeys with bilateral medial temporal lobectomies have major problems in forming long term memories for objects encountered in the delayed nonmatching-to-sample test -In this test, a monkey is presented with a distinctive object (sample object), under which it feinds food (banana pellet) -After a delay, the monkey is presented with 2 test objects: sample object + unfamiliar object -Monkey must remember the sample object so it can select the unfamiliar object to obtain food concealed beneath it -Intact, well-trained monkeys performed correctly on about 90% of these trials when the retential intervals were a few minutes or less but monkeys with lesions had major object-recognition defcits -These deficits modelled H.M's in key aspects: The monkey's performance was normal at delays of a few seconds but fell off to near chance levels at delays of several minutes, and their performance was very susceptible to disruptive effects of distraction -Humans with medial temporal lobe amnesia have been tested on the delayed nonmatching-to-sample test—their rewards were coins rather than banana slices—and their performance mirrored that of monkeys with similar brain damage. -Development of this test for monkeys provided a means of testing the assumption that the amnesia resulting from medial temporal lobe damage is entirely the consequence of hippocampal damage

What has research on medial temporal lobetaught us?

-Shown that H.M's difficulty in forming explicit long-term memroies while retaining ability to form implicit long-term memories of the same experiences is not unique to him -This problem = symptom of medial temporal lobe amnesia and many other amnesic disorders

Short-term memory

-Storage of information for brief periods of time while a person attends to it

How LTP is studied in rats

-Studying LTP in granule cell layer of rat hippocampal dentate gyrus 1) Single, low intensity pulse of current is delivered to perforant path (major input to dentate gyrus), and response was recorded through an extracellular multiple-unit electrode in the granule cell layer of the hippocampal dentate gyrus; this was to determine the initial response baseline 2) High intensity, high frequency stimulation lasting 10 seconds was then delivered to the perforant path to induce the LTP 3) Granule cell's responses to single pulses of low-intensity current was measured again after various delays -Transmission at granule cells' synapses was still potentiated 1 week after high-frequency stimulation

Islands of memory

-Surviving memories for isolated events that occurred during periods for which other memories have been wiped out

Morris water Maze Test

-Test of spatial memory in which rats must learn to swim directly to a platform hidden just beneath the surface of a circular pool of murky water -Intact rats placed a various locations learned to swim to the platform -Rats with hippocampal lesions learned this simple task with great difficulty

Reptition priming tests

-Tests of implicit memory -Incomplete-pictures test is an example, but repetition priming tests that involve memory for words are more common -First, asked to examine list of words, then shown a series of fragments of words from the original list and are simply asked to complete them -Controls who have seen the original words perform well, and participants wihth amnesia perform equally well

Mechanisms of induction of LTP

-The NMDA receptor is prominent at the synapses at which LTP is commonly studied -The NMDA receptor is a receptor for glutamate - main excitatory NT -An NMDA receptor does not respond maximally unless two events occur simultaneously: 1) Glutamate must bind to it 2) The postsynaptic neuron must already be partially depolarized. -This dual requirement stems from the fact that the calcium channels associated with NMDA receptors allow only small numbers of calcium ions to enter the neuron unless the neuron is already depolarized when glutamate binds to the receptors; it is the influx of calcium ions that triggers the cascade of events in the postsynaptic neuron that induces LTP. -When a more natural, low-intensity stimulation is applied, the postsynaptic neurons do not fire, and LTP is not induced - unless the postsynaptic neurons are already partially depolarized so their calcium channels are open wide when glutamate binds to their NMDA receptors -The requirement for the postsynaptic neurons to be partially depolarized when the glutamate binds to the NMDA receptors is an extremely important characteristic of conventional LTP because it permits neural networks to learn associations. -If one glutaminergic neuron were to fire by itself and release its glutamate neurotransmitter across a synapse onto the NMDA receptors of a postsynaptic neuron, there would be no potentiation of transmission at that synapse because the postsynaptic cell would not fire. However, if the postsynaptic neuron were partially depolarized by input from other neurons when the presynaptic neuron fired, the binding of the glutamate to the NMDA receptors would open wide the calcium channels, calcium ions would flow into the postsynaptic neuron, and transmission across the synapses between the presynaptic and postsynaptic neuron would be potentiated. -Accordingly, the requirement for co-occurrence and the dependence of NMDA receptors on simultaneous binding and partial depolarization mean that, under natural conditions, synaptic facilitation records the fact that there has been simultaneous activity in at least two converging inputs to the postsynaptic neuron—as would be produced, for example, by the "simultaneous" presentation of a conditional stimulus and an unconditional stimulus

Hippocampus and Consolidation: Standard consolidation theory

-The case of H. M. provided evidence of memory consolidation, and it seemed to suggest that the hippocampus played a special role in it. -To account for the fact that the bilateral medial temporal lobectomy disrupted only those retrograde memories acquired in the few years before H. M.'s surgery, it was suggested that memories are temporarily stored in the hippocampus until they can be transferred to a more stable cortical storage system -This theory became known as the Standard consolidation/dual-trace theory -Temporally graded retrograde amnesia is a feature of many forms of human amnesia (Alzheimer's, Korsakoff's); so it seems unlikely that the hippocampus plays a special role in consolidation -It appears that when a conscious experience occurs, it is rapidly and sparsely encoded in a distributed fashion throughout the hippocampus and other involved structures -According to Nadel and Moscovitch, retained memories become progressively more resistant to disruption by hippocampal damage because each time a similar experience occurs or the original memory is recalled, a new engram (a change in the brain that stores a memory) is established and linked to the original engram, making the memory easier to recall and the original engram more difficult to disrupt

Effects of closed-head injury on memory

-The coma (pathological state of unconsciousness) following a severe blow to the head usually lasts a few seconds or minutes, but in severe cases it can last weeks -Once the patient regains consciousness, he or she typically experiencs a period of confusion -Victims of concussion aren't tested until after period of confusion - and usually reveals that patient has permanent retrograde amnesia for events that led up to the blow and permanent anterograde amnesia for events that occurred during period of confusion -Anterograde memory defecits that follow a nonpenetrating head injury are often quite puzzling to friends and relatives who have talked to the patient during period of confusion -The patient may seem reasonably lucid at the time, because short-term memory is normal, but later may have no recollection whatsoever of the conversation -The duration of the period of confusion and anterograde amnesia is typically longer than that of the como, which is typically longer than period of retrograde amnesia -More severe blows to head will have longer comas, confusion, amnesia

.Describe 3 findings that have emerged from the study of the maintenance and expression phases of LTP

-The maintenance and expression of LTP involve changes in both presynaptic and postsynaptic neurons 1) LTP occurs only at specific synapses on a postsynaptic neuron: there must be a mechanism for keeping the events at one set of synapses on a postsynaptic neuron from affecting other synapses on the same neuron --> This specificity is due to the dendritic spines; the calcium ions that enter a dendritic spine do not readily pass out of it; and thus they exert their effects locally 2) Maintenance of LTP involves structural changes, which depend on protein synthesis. The discovery that LTP causes structural changes was exciting because the structure of neurons and neural circuits had been assumed to be static. Many kinds of structural changes have been described (e.g., increases in number and size of synapses, increases in number and size of postsynaptic dendritic spines, changes in presynaptic and postsynaptic membranes, and changes in dendritic branching), and the changes have turned out to occur far more rapidly and more frequently than was once assumed 3) The discovery of structural changes in neurons following the induction of LTP stimulated a search for a mechanism by which a neuron's activity could change its structure. This led to the discovery of numerous transcription factors (intracellular proteins that bind to DNA and influence the operation of particular genes) that were activated by neural activity

Mumby box

-The version of the delayed nonmatching-to-sample test for rats that most closely resembles that for monkeys was developed by David Mumby using an apparatus that has become known as the Mumby box -Sample object is placed over one food cup at one end, and object identical to sample object is placed over the two food cups at the othe end -When sliding door is raised, exposing the sample object, a trained food deprived rat runs down to sample object + pushes it acide and a piece o food is delivered to the exposed food cup -Sample object is immediately removed after, and rat remains at same end of box until prescribed delayed period is over -THen, sliding door is raised to expose 2 objects at other end -Trained rats will remember previous encounter w/ sample object so it will run to novel object and push it aside, and food is delievered to exposed food cup -The rat runs to the center of box, sliding door closed behind it, then new objects are arranged for next trial -Rats perform almost as well as monkeys with delays of up to 1 minute -The validity of the rat version of the delayed nonmatching-to-sample test has been established by studies of the effects of medial temporal lobe lesions. As in humans and monkeys, bilateral lesions of the rats' hippocampus, amygdala, and medial temporal cortex combined produce major deficits at all but the shortest retention intervals

Reconsolidation

-Theory that each time a memory is retrieved from long-term storage, it is temporarily held in a labile (changeable/unstable) state in short-term memory, where it is susceptible to posttraumatic amnesia -This susceptibility remains until it is consolidated again (i.e., reconsolidated) -Researchers infused protein-synthesis inhibitor anisomycin into the amygdalae of rats shortly after the rats had been required to recall a fear conditioning trial. The infusion produced retrograde amnesia for the fear conditioning, even though the original conditioning trial had occurred many days before -Most research on reconsolidation has involved fear conditioning, but some evidence suggested that it may be a general phenomenon in the nervous system

How can ischemia-produced lesions to one small part of the hippocampus be associated with severe deficits in performance on the delayed nonmatching-to-sample test when the deficits associated with total removal of the hippocampus are only modest?

-This line of evidence suggests that damage to brain structures other than the hippocampus contributes to the amnesia observed in patients following global cerebral ischemia -Indeed, although the most obvious damage following cerebral ischemia is in the CA1 subfield of the hippocampus, there is substantial damage to other areas that is more diffuse and thus more difficult to quantify -Allen and colleagues (2006) found that ischemic patients with a greatly reduced hippocampal volume were much more likely to suffer from anterograde amnesia; however, these same patients also tended to have extensive neocortical damage.

Cerebellum

-Thought to participate in storage of memories of learned sensorimotor skills thourhg its various neuroplastic mechanisms -Its role in the Pavlovian conditioning of the eye-blink response of rabbits has been most intensively investigated -In this paradigm, a tone (conditional stimulus) is sounded just before a puff of air (unconditional stimulus) is delievered to the eye -After several trials, the tone comes to elicit an eye blink -Effects of this conditioning are stored in the form of changes in the way the cerebellar neurons respond to the tone

Striatum and memory

-Thought to store memories for consistent relationships between stimuli and responses - the type of memories that develop incrementally over many trials -Sometimes this striatum-based form of learning is referred to as HABIT FORMATION -Patients with Parkinson's who had striatal damage, could NOT solve a probabilistic discrimination problem -The problem was a computer "weather forecasting game", and the task was to correctly predict the weather by pressing one of two keys: rain or shine -The patients based their predictions on stimulus cards presented on the screen—each card had a different probability of leading to sunshine, which the patients had to learn and remember. The patients with Parkinson's did not improve over 50 trials, although they displayed normal explicit (conscious) memory for the training episodes. In contrast, patients with amnesia with medial temporal lobe or medial diencephalic damage displayed marked improvement in performance but had no explicit memory of their training.

H.M's memory

-Unqualified success in that incidence of seizures was markedly reduced -Left in nearly the same condition with perceptual and motor abilities -H,M's memory for events predating his surgery remained largely intact (retrograde) -Biggest problem was long-term anterograde amnesia -Had pretty normal short-term antergrade memory: digit span test normal -Once H.M stopped thinking about a new experience, it was lost forever: never learned to recognize people who he didn't meet until after surgery, could read same thing over and over again without finding them familiar

What can we determine from placing a rat in an ambigious situation in a familiar test environment?

-We could determine where the rat thinks it is from the route that it takes to get to the location in the environment where it has previously been rewarded -Researches have shown that firing of a rat's place cells indicates where the rat "thinks" it is in the test environment, not necessarily where it actually is

Infantile Amnesia

-We remember virtually nothing of the events of our infancy -Newcombe and colleagues (2000) addressed the following question: Do normal children who fail to explicitly recall or recognize things from their early childhood display preserved implicit memories for these things? YES -In one study of infantile amnesia (Newcombe & Fox, 1994), children were shown a series of photographs of preschool-aged children, some of whom had been their preschool classmates. The children recognized a few of their former preschool classmates. However, whether they explicitly remembered a former classmate or not, they consistently displayed a large skin conductance response to the photographs of their former classmates but not to the control photographs. -In a second study of infantile amnesia, Drummey and Newcombe (1995) used a version of the incomplete-pictures test. First, they showed a series of drawings to 3-year-olds, 5-year-olds, and adults. Three months later, the researchers assessed the implicit memories for these drawings by asking each participant to identify them ("It's a car," "It's a chair," etc.) and some control drawings as quickly as they could. During the test, the drawings were first presented badly out of focus, but became progressively sharper over time. Following this test of implicit memory, explicit memory was assessed by asking the participants which of the drawings they remembered seeing before. The 5-year-olds and adults showed better explicit memory than the 3-year-olds did; that is, they were more likely to recall seeing drawings from the original series. However, all three groups displayed substantial implicit memory: All participants were able to identify the drawings they had previously seen sooner, even when they had no conscious recollection of them.

Hypotheses for causes of Amnesia in Korsakoff

1) First hypothesis was based on several small postmortem studies. Damage to the mamillary bodies of the hypothalamus = responsible for memory deficits of patients with Korsakoff; however, subsequent studies revealed cases of Korsakoff amnesia with no mamillary body damage. But in all of these exceptional cases, there was damage to another pair of medial diencephalic nuclei: the mediodorsal nucliei of the thalamus. -It is unlikely that the memory defecits of patients with Korsakoff are attributable to the damage of any single structure

3 parts of LTP

1) Induction 2) Maintenance 3) Expression -The processes by which high-frequency stimulations induce LTP (learning), the changes responsible for the maintenace of LTP (memory), and the changes that allow it to be expressed during the test (recall)

2 reasons for initial difficulty in developing an animal model of medial temporal lobe amnesia

1) It wasn't initially apparent that H.M's anterograde amnesia didn't extend to all kinds of long-term memory - that it was specific to explicit lT memories, and most animal memory tests in the 50s and 60s were tests of implicit memory (Pavlovian + operant conditioning) 2) It was incorrectly assumed that amnesic effects of medial temporal lobe lesions were largely, if not entirely, attributable to hippocampal damage; and most efforts to develop animal models of medial temporal lobe amnesia focused on hippocampal lesions

Support for the idea that LTP is related to neural mechanisms of learning and memory

1) LTP can be elicited by low levels of stimulation that mimic normal neural activity 2) LTP effects are most prominent ins structures that have been implicated in learning and memory, such as the hippocampus 3) Learning can produce LTP-like changes in the hippocampus 4) Many drugs that influence learning and memory have parallel effects on LTP 5) The induction of maximal LTP blocks the learning of a Morris water maze until the LTP has subsided 6) Mutant mice that display little hippocampal LTP have difficulty learning the Morris Water Maze 7) Behavioural changes that appear to be memories can be induced in mice via LTP 8) LTP occurs at specific synapses that have been shown to participate in learning and memory in simple invertebrate nervous systems

2 key properties of LTP that Hebb proposed as characteristics of physiological mechanisms of learning and memory

1) LTP can last for a long time - for several months after multiple high frequency stimulations 2) LTP develops only if the firing of the presynaptic neuron is followed by the firing of the postsynaptic neuron; it doesn't develop when presynaptic neuron fires and postsynaptic doesn't, and it does not develop when the presynaptic neuron does not fire but postsynaptic does

2 categories of explicit long-term memories

1) Semantic memories: explicit memories for general facts/ information 2) Episodic memories: explicit memories for particular events (episodes) of one's life

3 major scientific contributions of HM's case

1) Showed that medial temporal lobes play an important role in memory. Challenged the then prevalent view that memory functions are diffusely and equivalently distributed throughout the brain. Renewed efforts to relate individual brain structures to specific mnemnic (memory-related) processes; in particular, at clarifying the mnenomic functions of hippocampus + other medial temporal lobe structures 2) Discovery that he had difficulty forming certain kinds of LT memories without disruption performance on test of ST memory or his remote memory (memory for experiences in distant past), supported the theory that there are different modes of storage for ST, LT, and remote memory. H.M's specific problem = difficultyi n MEMORY CONSOLIDATION: transfer of ST memories to LT storage 3) H.M's case was the first to reveal that a patient with amnesia might claim no recollection of a previous experience while demonstrating memory for it by improved performance (mirror-drawing and incomplete-pictures test). Led to creation of 2 distinct categories of Long Term memroeis: Explicit and Implicit memories

2 lines of evidence that suggest the responses of hippocampal palce cells depend on input from entorhinal grid cells

1) There is a major pathway from the entorhinal cortex to the hippocampus. 2) Entorhinal grid cells respond relatively reflexively to location, whereas hippocampal place cells respond to place in combination with other features of the test environment -However, the discovery that the properties of hippocampal place cells emerge in developing rat pups prior to the emergence of stable entorhinal grid cell firing challenges the idea that input from entorhinal grid cells is essential for hippocampal place cell function -Moreover, there is evidence that place cells can still function after entorhinal grid cells have been eliminated

3 major structures of the medial temporal lobe

1) hippocampus 2 ) amygdala 3) medial temporal cortex

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