Module 3 Flashcards
What was the surgery that was performed on H.M and why
medial portions of his temporal lobe removed to treat epilepsy
- called a bilateral medial temporal lobectomy
what structures specifically were removed in the case of HM
most of the hippocampus, amygdala, and adjacent cortex
what is the difference between a lobectomy and lobotomy
ectomy = fully removed botomy = connections to other areas severed
what were the successful aspects of HM’s surgery (3)
- generalized seizures eliminated
- partial seizures down from several per day to at most 2, even tho he was taking less anticonvulsants
- his IQ increased
what were the unsuccessful aspects of HM’s surgery?
- mild retrograde amnesia for events within 2 years before his surgery
- short term memory was fairly normal (digit span was nearly normal)
- long term memory anterograde amnesia was entirely removed, once something left his short term memory, it was gone
what is retrograde amnesia
backward acting, loss of memories derived from experiences before the onset
what is anterograde amnesia
forward acting, loss of memories derived after the onset
what are the two mechanisms of anterograde amnesia
short term memory problems - can’t hold things in short term
long term - can’t encode short term mems for long term storage
What is the Digist span +1 test and what does it diagnose? How did HM perform?
tests verbal long term memory
repeat 5 digits at 1 second intervals, if good, add one on the next trial
normal is 15 digits after 25 trials
he got 8
what is the Block-tapping memory-span test and what does it diagnose? how did HM perform?
Tests for Global amnesia (as opposed to the verbal digit test) - same procedure but taps blocks in order.
had a normal span of 5, but could never learn 6
what is the mirror drawing test, what does it measure, and how did HM perform/
Tests implicit memory storage, in which HM performed just fine (improved each time) despite not recalling ever having taken it before. thought that it was purely sensorimotor learning that he could do…
what is the incomplete picture test, what does it measure and how did HM pervform
Nonsensorimotor test that employs sets of fragmented drawings where you try and identify it at most fragmented, then less and so on until correct.
again, HM got better with time without recalling performing the task
Could HM learn through pavlovian conditioning?
yes, but slower than is typical
what are the three major scientific contributions of HM’s case?
- demonstrating the importance of the medial temporal loves in memory, challenging the view that memory function was distributed throughout the whole brain - spawned research aimed at understanding the mnemonic role of the hippo etc.
- Separated memory into short term, long term and remote, and introduced the concept of memory consolidation (short term to long term) which HM struggled with
- Differentiated between implicit and explicit memories, the second of which HM had trouble with
what is medial temporal lobe amnesia?
the profile of mnemonic deficits similar to those of HM that present with preserved intellectual functioning and evidence of medial temporal damage
maintenance of the ability to form implicit long term memories, but not explicit
what do we call tests that measure implicit memory capacities? describe them
repetition priming tests, ex the incomplete pictures test, but most often using words (A___H__E, even those with explicit amnesia perform about as well as controls)
what is the evolutionary explanation for the distinction between the implicit and explicit memory systems?
Implicit probably arose first (simpler), so we must as why do we have conscious memories at all?
What do experiments suggest is the reason for the conscious (explicit) memory system?
describe the studies that looked at this
flexibility!
1. patients with amnesia
2. monkeys with medial temporal lobe lesions
both learned implicit tasks as well as controls, but if they were asked to use this knowledge in a new, but similarly engaged, context, they failed to do so.
- so, it looks like it arose to allow us to generalize learning to broad situations
are most people with medial temporal lobe amnesia as incapable of forming explicit memories as HM?
no, most struggle with episodic rather than semantic memories
what are episodic memories
explicit memories for particular events of one’s life
what are semantic memories
explicit memories for general facts or information
what is another term for episodic memories
autobiographical
Describe the case of Tulving’s patient KC
completely normal semantic memory, but complete inability to perform mental time travel to the past or future, and inability to remember any episodic memories
describe the Vargha-Khadem study on medial temporal lobe amnesia
followed the maturation of 3 people with the damage from early life - they processed through all of the typical stages in school and what not with not improvement in their episodic memory
is it easy to diagnose episodic memory deficits?
no, sometimes patients are good at filling in, but one can ask very specific and pointed questions that can only be answered by reference to a particular experience
what is global cerebral ischemia, and what does it often cause
complete loss of blood to their entire brains,
- often medial temporal lobe amnesia
where was the damage to R.Bs brain mostly found (the bungled operation)
- what did this suggest in reference to medial temporal lobe amnesia
- why isn’t this conclusive evidence?
the pyramidal cell layer of the CA1 subfield of the hippocampus
- maybe dmg to the hippo is alone sufficient to induce mt amnesia
- but in the case of global cerebral ischemia, we can’t tell if theres other damage thats just harder to spot
what is the strongest evidence that selective hippo dmg can cause medial temporal lobe amnesia? define and explain
- transient global amnesia
sudden onset of severe anterograde amnesia and moderate retrograde amnesia for explicit memories
amnesia tends to only last for 4-6 hours - we have found damage to the same CA1 subfield of the hippo as in the case of RB
what is Korsakoff's syndrome explain those it effects (1) explain phsyiological cause (1) explain symptoms (5) explain neurological pathology and their loci (3/4 depending)
- memory disorder common in people who have consumed a lot of booze
- largely attributed to the brain damage associated with the thiamine deficiency that accompanies heavy alcohol consumption
- sensory and motor problems, extreme confusion, personality changes, risk of death from liver, gastrointestinal or heart disorders
- lesions to the medial diencephalon (medial thalamus and hypothalamus)
- diffuse damage to other brain structures (neocortex, hippocampus and cerebellum)
what are the similarities between the symptoms of Korsakoff’s syndrome and MT amnesia?
early stages of Korsakoff’s - anterograde, explicit, episodic amnesia is the most prominent
- there do appear to be problems with implicit memory, depending on the test, but less severe than explicit
what are the main differences between Korsakoff’s and MT amnesia in terms of symptomology
Progression…
1. middle stages - retrograde amnesia into childhood
why does the insidious onset of Korsakoff’s make it difficult to study the resulting retrograde amnesia?
never clear whether amnesia for recent events is because of retrograde or anterograde blockage
what has been a problem with identify which part of Korsakoff’s brain deterioration is the cause of amnesia?
how diffuse the pathology is
what was the first hypothesis pertaining to the neural basis of korsakoff amnesia
what disproved this?
damage to mammillary bodies of the hypothalamus was responsible
- cases of Korsakoff’s where there was no pathology to these bodies
what do we now believe to be the neural basis of Korsakoff’s amnesia? is it probably this site alone?
damage to the mediodorsal nuclei of the thalamus
Nah, probably fairly diffuse
what is Medial encephalic amnsesia
amnesia like that found in Korsakoff syndrome, where there is damage to medial diencephalon
Describe the case of medial encephalic amnesia in NA
what brain structures were damaged? (3)
stabbed through his cribriform plate into his brain
- unable to recall any events that occurred 2 years before his accident
- when retested 3 years later, his retrograde amnesia had decreased in duration, covering only those events than had happened 2 weeks before
- slight imrpvmt of day to day recall, recalling random memories of no significance
MRI found extensive medial diencephalic damage, including damage to the mediodorsal nuclei and mammillary bodies
where have efforts to study the neural basis of Alzheimer’s amnesia focussed? why?
predementia patients with alzheimers, who have much more general memory deficits than those with any of the other disorders we’ve spoken about
- major anterograde and retrograde deficits in explicit memory
- deficits in short term memory
- some deficits in implicit memory
- ie; verbal and perceptual material is deficient
- sensorimotor learning is fiiiine
what is the leading theory of why patients with alzheimers have amnesia?
greatly diminished levels of acetylcholine
which brain structure is degenerated in Alzheimer’s patients leading to the decrease in ACH
the basal forebrain, a midline area just about the hypothalamus, the brains main source of the neurotransmitter.
what is a piece of evidence that suggests that the basal forebrain and ACH is causal in Alzheimer’s amnesia?
strokes in the basal forebrain also cause amnesia
do we believe that aCH deficiencies are the sole cause of Alzheimer’s amnesia?
no, there is a lot of diffuse brain deterioration
this includes areas like the medial temporal lobes and prefrontal cortex which are super relevant for memory
what do we call amnesia following a non penetrating blow to the head
Posttraumatic amnesia
can we get comas after head trauma
yes, they usually last for only a little while but can last for weeks in severe cases
what do people who suffer from non-penetrating head trauma experience when they wake up from a coma?
confusion
when do we test people who have had head trauma
what does this testing usually reveal
after the period of confusion if at all.
- reveals permanent retrograde amnesia for the events leading up to the blow and anterograde during the confused period
why are the memory deficits associated with closed head injuries so strange?
because the person might seem perfectly lucid during their confused state and them remember none of that shit
describe the durational hierarchy that is common in closed head injuries
confusion and anterograde period is longer than the coma, which is longer than the period of retrograde
what do more severe head injuries tend to produce?
longer comas, periods of confusion and amnesia
what are islands of memory
surviving memories for isolated events that occurred during periods for which other memories have been wiped out
what does the gradient of retrograde amnesia after concussion provide support for? why?
memory consolidation, the fact that older memories are preserved suggests they have been strengthened (consolidated)
explain Hebb’s theory of memory consolidation
short term memories are stored by reverberating or circulating neural activity in closed circuits, which can be disrupted by trauma leading to memory loss. Once they induce structural changes in the involved synapses (consolidation) they become more stable.
what have proven to be a good method of studying memory consolidation in a controlled environment
electroconvulsive shock treatments which attempts to stop consolidation by disrupting the neural activity, hopefully only erasing short term memory and leaving the longer, structurally stored memories intact.
what do ECS experiments allow us to estimate in theory?
The length of the period of retrograde amnesia produced would provide an estimate for the amount of time it takes to induce consolidation
what doe ECS studies show about Hebb’s theory?
consolidation probably takes a lot longer than he anticipated
Describe the Squire, Slater and Chase study on ECS induced retrograde amnesia
Five ECS treatments disrupted memory of information pertaining to TV shows that had been played within the last three years, but not earlier
what its he current view of memory consolidation
continues for a very long time, if not indefinitely
- lasting memories become more and more resistant throughout ones life
- each time we activate a memory, it is updated, linked with other ones, which increase its resistance to disruption
what is the standard consolidation theory? whaat is another name for it?
the theory that memories are stored in the hippo until they can be transferred into more stable cortical storage
aka dual trace theory
is the standard consolidation theory still widely accepted? why or why not?
no, temporally graded amnesia is in a lot of types of amnesia, so its unlikely that the hippo plays any special role
what is the more modern version of the dual trace theory
when conscious experience occurs, it is rapidly and sparsely encoded in a throughout the hippo and other structures
what was Nadel and Moscovitch’s position on the reason for the increase in memory resistance over time?
each time a similar experience occurs or an original memory is recalled, a new engram (brain change that stores a memory) is established and linked to the original, making the memory easier to recall and the original harder to disturb
what is an engram
a brain change that stores a memory
define reconsolidation
each time a memory is retrieved from long term storage, it is temporarily held in labile (unstable) short term memory, where it is once again susceptible to trauma
Describe the Nader, Shafe and Ledoux study on memory reconsolidation
infused a protein-synthesis inhibitor anisomycin into the amygdalae of rats right after the rats had recalled a fear conditioning trial
- produced retrograde amnesia for the fear conditioning, even tho the original conditioning trial had occurred days before
why are animal models of amnesia relevant
many important questions can only be answered by controlled experiments, such as which particular structures are pertinent in such and such a disorder, which often have to do with making lesions and testing their behavioural effects
why were early attempts to replicate medial temporal lobe amnesia in animals unsuccessful?
they didn’t producce severe anterograde amnesia in rats, monkeys or any other non-human species
what were the two reasons that early attempts to replicate medial temporal lobe amnesia in animals was unsuccessful?
- not apparent that His amnesia did not extend to all kinds of long term memories (his was only explicit, and most animal studies test implicit memory)
- Incorrectly assumed that the amnesic effects of mt lobe lesions were nearly entirely due to hippocampal damage, so most studies focussed on this damage
what did the first successful studies on mt lobe damage models in non-human animals show?
monkeys with bilateral medial temporal lobectomies have problems forming long term memories for objects encountered in the delayed non matching-to-sample test
what is the delayed non matching-to-sample test?
- monkey is presented with a sample object under which it finds food
- after delay, the monkey is presented with 2 objects, sample and unfamiliar
- monkey must remember the sample object to find the food
how do healthy monkeys perform on the non matching to sample test? how to those with bilateral medial temporal lobe ectomies?
healthy - good at around 90%
damage 1. fine at intervals of a few seconds but go down to chance levels after a few minutes
2. extremely susceptible to the disruptive effects of distraction
how do humans with medial temporal lobe amnesia perform on the non matching to sample test?
the same as monkeys with the damage,
what did the dev. of the delayed nonmatching to sample test allow us to test experimentally?
the assumption that medial temporal lobe amnesia is the result of hippo damage
what were the three main areas that were damaged in the monkeys that participated in the delayed non matching to sample test?
hippo, amygdala and medial temporal cortex
why is the study of rats with hippocampal lesions a better way of examining the hippocampus causes amnesia assumption? (3)
- bc of size and location, all studies of hippocampal lesions in monkeys involved the aspiration (suction) of a lot of the mt cortex as well
- in rats, its limited to small area of the parietal context
- rat hippo is so small it can be lesions electrolytically or with intracerebral neurotoxin injections which produce less extraneous damage
Explain the Mumby box and why it was developed (3)
- placed in a box with two sliding doors n either side, one side has object a and a food cup, other side has object a and object b
- open door to side w object a and food cup, runs to object and pushes it over to find food
- upon other door being opened, it will run to the novel object to check for food
- tries to model the delayed non-matching to sample test
how well do rats perform on the mumby box test
about as well as monkeys up to 1 minute
how did we show that the mummy box was a valid measure of medial temporal lobe damage?
bilateral lesions of rats hippo, amygdala and medial temp cortex together produce major problems in all but the shortest retention intervals
what did tests on selective surgical lesions suggest about the hippo assumption? (4)
- bilateral medial temp cortex lesions produced sever and permanent effects on the delayed nonmatching sample test
- hippo lesions produced moderate deficits
- amygdala lesions produce none
- hippo plus amygdala still prod less than the medial temporal lesions
why did the studies that contradict the hippo theory of amnesia cause us to re-examine cases like R.B?
after his global cerebral ischemia, he had obvious cell loss in only the pyramidal cell layer of his CA1 hippocampal subfield, which has been replicated in monkeys and rats
- this yields significant problems with the delayed nonmathcing-to-sample test
what did revoking the hippo theory reveal about cases like R.B?
there is also substantial damage to the neocortex more generally, especially in those with anterograde amnesia, which is fairly diffuse and hard to quantify
what do structures of the medial temporal lobes play a role in specifically in terms of memory
explicit, episodic memories
Almost all studies of hippocampal lesions in monkeys and humans entail damage to large portions of what structures in addition to the hippo?
- what does this contain
Rhinal cortex
- composed of the entorhinal and perirhinal cortex
what do studies on hippocampal lesions reveal about the types of memory that they do severely impact?
what two tests show this?
spacial location!!
- Morris water maze
- radial arm maze tests
what is the Morris water maze test
healthy rats placed in a circular pool of murky water will learn to swim to a stationary platform pretty fast
those with hippo dmg will NAHT
what is the radial arm maze test?
how do healthy rats perform?
how do those w hippo dmg perform?
several arms radiate out from a central starting chamber and the same few are baited with food each day
- intact rats learn to visit the arms that tend too have food and dont visit the other arms more than once a day
- major deficits in inhibiting visits to the ones with no food and selecting those with food
what two types of memory does the radial arm maze test for?
- reference memory - memory for the general principles and skills required for a task
- working memory - temporary memory necc for successful performance of a task on which on is currently working.
what does working memory predict?
reading comprehension, analytic ability and complex reasoning
is working memory a state or a trait?
both! can be influenced by the environment but is also a general disposition
what are the three processes of memory
encoding, storage and retrieval
what are the three basic systems off memory
sensory (first seconds), short term (20 seconds), long term memory
what is what is long term memory divided into?
- declarative memory - stores and retrieves facts
2. procedural memory - remember how to do things
what is the cell type of a lot of hippo cells?
what are these?
place cells, which respond only when the subject is in specific locations
how do place cells learn their specific locations
no place cells get activated when a rat is in a new place, but as they learn they become accustomed
what do place cell activations actually show?
that they fire only when we think were in a place, not when were actually in it (assuming the two dont match up)
what is a major area of focus on the study of hippo place cells
the entorhinal cortex, which is an area of the medial temp cortex that is a major source of neural signals to the hippo
how do we think that hippocampal place cells obtain their spacial information?
grid cells in the entorhinal
what are grid cells
entorhinal neurons that each have an extensive array of evenly spaced place fields, producing a pattern like graph paper, with the spacing being flexible
how do small or oddly shaped environments influence the distribution of grid cells?
closer together or sheared, respectively
how do we think grid cells influence place cells?
their even distribution could allow for spacial computation in place cells
are grid cells unique to humans
no
what are the other types f neurons in the entorhinal cortex that are associated with spacial location?
- head-direction cells; tuned to the direction of head orientation
- border cells; fire when u are close to the border of ur environment
what are the two lines of evidence that suggest that grid cells are necc for place cells to functin
- major pathway from entorhinal to the hippo
- entrhinal grids respond relatively reflexively to location, whereas hippo place cells respond to location in combo with other features of the env
what’re the two main =points evidence against the view that grid cells are necc for hippo place cells?
- in developing rats, hippocampal place cells develop prior to the emergence of a stable entorhinal grid cell firing
- even when grid cells are eliminated, place cells can still function
what species of bird has been involved in hippo function?
what does evidence suggest?
food caching, cuz they need to have great spacial memory.
indeed, they have massive hippos relative to the rest of the brain and relative to related nonfood caching species
why do we think that studies on hippo dmg and spacial location memory in humans and primates are less conclusive than other species?
- bc we are often tested on a computer, as opposed to in a maze or otherwise
what other forms off memory has the hippo been implicated in recently? (3)
- code for temporal aspects of expereicen, called ‘time cells’
- social organization (social space) in humans
- conceptual coding
why are epileptic recording electrodes good for the study of neuronal activity, especially in terms of memory?
bc they get these a lot, and they are often focussed on the medial temporal lobe bc they’re so susceptible to epilepsy
what three cortical structures compose the medial temporal cortex
- entorhinal
- perirhinal
- parahippocampal
what are Jennifer Aniston neurons?
a neuron that fired specifically to her picture in a patient, but we now know that individual neurons fire specifically for particular known faces
what are the two features of Jen Aniston neurons?
- selectivity - respond only to one or a few test objects
2. invariability - if they respond to a face once they will always respond to that face
why are Jen anniston hippo cells unique amongst that type?
they are more selective and more invariant
what is another word for the Jen Aniston cells, and why? (2)
concept cells, bc they respond to ideas or concepts rather than particular features, and will respond across modalities to that concept.
what are two neat facts about the concept cells?
- they are liable to error - if I think it is a instead of b when it is actually b, the concept cell for a will fire
- ambiguous photos (synthesized pcictures, duck-rabbit) fire only when the viewer perceives the concept the cell is attuned for!
why do concept cells fire for more than one concept when they do?
what does this lead to hypothesizing
they are typically highly related conceptually, which is why we now think that images trigger activity in concept cell circuits in the medial temp lobes
what is optogenetics
inserting an opsin gene into a particular neuron, which can be hyper or de-polarized by light
what have we recently used optogenetics to try and discover
engram cells, which maintain an engram
what are the two stages of identifying engram cells via optogenetics?
- tagging stage - neurons active during a learning task are induced to express opsin
- manipulate stage - polarization by light
what does optogenetics allow in terms of engram cells?
to observe, suppress or activate them in different parts of the NS
what are two examples of the utility of engram cell manipulation via optogenetics?
- can reverse depressive behaviour in mice by reactivating himppocampal dentate granules cells that had been activated during the encoding of a positive experience
- in transgenic alzheimers mouse models, activating engram cells leads to the retrieval of memories that are otherwise inaccessible
what does the utility of ontogenetic manipulation of engram cells in mouse alzheimers models suggest about the disease? why?
- that memory deficits are retrieval in nature rather than encoding, bc they are retrievable when the engrams are stimulated
what is the common method of studying which brain areas are the locus of memory storage? is this successful? what has this revealed (2)?
- lesions to areas where memories are stored should result in the loss of that type of memory
- didn’t work, tend to produce either no retrograde, or retro for only those experiences that occurred in the days or weeks prior to surgery
- i) memories are stored diffusely around the brain and can survive single structure destruction
3 (ii) memories become more resistant to disruption over time
what brain regions are involved specifically with episodic memory (2)
hippo and medial temporal
what brain regions are involved specifically with memory deficits associated with Korsakoff’s and alzheimers, respectrively>?
Kors - mediodorsal nucleus of the thalamus
alz - basal forebrain
what do areas of the brain active during an experience tend to also be active during?
what has this led to? which area specifically?
the retention of an experience
- studies of the mnemonic functions of the sensory and mortar areas of the brain, specifically the inferotemporal cortex
what is the inferotemporal cortex and what is its main function?
the cortex of the inferior temporal cortex
complex visual functions
what did Bussy and Sakisida argue about the inferior temporal cortex?
in conj with the adjacent perirhinal cortex, it plays an important role in sorting memories of visual input
How did the naya, Yoshida and miyashita study support the bussy and sakisida study? and what was their study/
recorded the responses of neurons in the inferotemporal and perirhinal cortex while monkeys learned the relation between the two items in pairs of visual images
- when the pairs were presented, responses were recorded in the infero then the perirhinal, vice versa during recall
- suggests that the reversed pattern of activity reflects the retrival of visual memories from the inferotemporal
what do we think the amygdala does specifically in terms of memory?
what findings show this? (2)
emotion significance of experience
- rats with amygdala lesions do not get scared at a neutral stem that has been followed by electric shocks
- patient with bilateral dmg to amygdala could not acquire the conditioned autonomic state response to various visual or auditory stimuli, despite remembering the training
what do we think specifically about the role of the amygdala?
it doesn’t store memories, appears to be involved in strengthening the emotionally significant memories stored in other structures
- might even be the reason why emotional memories are remembered better than neutral ones
what do patients with dmg to the prefrontal Cortex demonstrate?
not gross amnesia, tend to display no problems on our typical memory tasks
- this is bc different parts play different roles in memory
what are the two episodic memory abilities that tend to be lost by patients with large prefrontal lesions?
- anterograde and retrograde deficits in memory for the temporal order of events
- working memory deficits
what do patients with large prefrontal lesions tend to have trouble with
performing tasks the involve a series of responses
what are two memory functions assoc with prefrontal cortex thru functional brain imaging studies?
- fundamental cognitive proc during working memory tasks
2. other regions participate in other
where do we believe implicit memories of sensorimotor tasks are stored?
in other sensorimotor circuits, particularly the cerebellum and striatum
what do we believe the cerebellum contributes to sensorimotor memory and how?
storage of memories off learned sensorymotor skills due to its neuroplastic mechanisms
what is the main method we’ve studied the role of cerebellum in memory?
Pavlovian eye conditioning studies in mice, stimulation, lesion and recording studies suggest its due to the changes in the way the cerebellar neurons respond to the tone
what do we call striatum based learning, and why?
habit formation, because it stores memories for consistent relationships between stem and responses
explain the study that suggests that the striatum and cerebellum play roles in more than sensorimotor learning
ppl with parkinsons with striatal dmg could not solve a probabilistic discrimination problem (shown whether cards w diff chances of predicting rain, couldn’t learn, even tho those they had explicit memory of learning)
what is long term potentiation
the facilitation of synaptic transmission following high-frequency elec stimulation applied to presynaptic neurons (stimulation increases ease in the future)
explain the three steps to producing LTP in Rodents
- single, low intensity pile delivered to the perforate path (main input to dentate gyrus), response was recorded (in the granule cell layer of the dentate by an extracellular electrode) to establish baseline
- high intensity and frequency stimulation of 10s delivered to the perf path
- granule cells responses to single puses of low intensity were measured after various delays
- after a week, still potentiated
how does LTP relate to Hebb’s theory of memory?
they are similar in kind to the synaptic changes that he hypothesized caused long term memory
what are the two key properties that LTP shares with Hebb’s theory?
- LTP can last for a long time, up to several months after multiple high frequency stims
- develops only if pre then post syns fire, not if a does and not b, not if b does but not a.
what is now recognized as the critical factor in LTP?
what would Hebb call this?
co-occurance between pre and post synaptic neurons.
the assumption that this is necessary is called ‘Hebb’s postulate for learning.
what are the 8 pieces of support for the idea that LTP is related to the neural mechanisms of learning and memory
- LTP can be elicited by low lvls of stim that mimic normal neuron firing
- effects are most prominent in structures that have been implicated in learning and memory
- learning can produce LTP like changes the hippo
- many drugs that Influence learning and memory have parallel effect on LTP
- induction of maximal LTP blocks the learning of a Morris water maze until the LTP has subsided
- mutant mice who do not show LTp in the hippo cannot learn the Morris water maze
- behavioural changes that appear to be memories cane be caused by LTP in mice
. LTp occurs at specific synapses that have been shown to precede learning and memory in invertebrate systems
regarding LTP, what is important to bear in mind?
all the evidence for it is indirect, and that LTp induced in the lab is at best a rudimentary model of the cellular events that cause learning
what are the three parts to LTP that reserachings are now investigation
- Induction (learning)
- maintenance (memory)
- expression (recall)
what is the prominent receptor at the synapses where we study LTP
NMDA receptor for glutamate, the main excitatory neurotransmitter
what are the two (simultaneous) requirements for the proper functioning of an NMDA receptor?
why?
- glutamate must bind to it
- postsyn neuron must be already partially depolarized
- calcium channels associated with NMDA receptors allow only a small number of Ca2+ ions to enter unless it is already depolarized when glutamate bonds
- it is the influx of Ca2+ that triggers the cascade f events in the post syn neuron that induces LTP
are the two simultaneous requirements for LTP in NMDA receptors identical in both natural and experimental conditions? why?
no, in experimental conditions the high intensity stim activated the postsynaptic neuron through massive temporal and spacial summation
- when in nature, the depolarization and binding of NMDA is required to make them fire (due to less intense activation)
why is the 2 part requirement for naturally induced LTP in NMDA receptors important?
allows the neural network to learn associations
why does the 2 part requirement for naturally induced LTP in NMDA receptors allow the neural network to learn associations?
(what are the differences between the neural network if post synaptic neurons haven’t been depolarized vs if they have, and what does this mean)
- if one glutaminergic neuron fires by itself, there would be n transmission bc the post syn neuorn would fail to fire.
- if the post syn had already been depolarized by input from other neurons, then transmission across the synapse would be potentiated
- means that synaptic facilitation records input from more than two sources as is the case with natural systems
Where do the mechanisms of LTP exert their influence?
both pre and post synaptic neurons
how is LTP able to occur at only one synapse despite the fact that neurons have many?
Dendritic spines do not allow calcium ions to enter the Neuron more generally
what are the interesting structural effects of LTP
increases in number and sizes of synapses, number and size of post syn dendritic spines that occur fast and more frequently ,
what do we think is the reason for the structural changes found in LTP?
Transcription factors, which are intracellular proteins that bind to DNA and influence the operation of iartiulcar genes, which are also known to be activated by neural activity
what are the four reasons that LTP is more complex than originally thought?
- NMDA-receptor mediated LTP involves a very complex array of changes
- Hs been documented in other areas of the CNS (not just the hippo)
- LTD exists (long term depression) which is the opposite of LTP and occurs in response to a lot of low frequency stim of the presynaptic neurones
- Metaplasticity, LTP and LTD induction can be modulated by prior synaptic activity
What kind of memories are lost in infantile amnesia? do any survive?
explicit, yes, implicit recall is preserved
What are the two studies that show the preservation of infantile implicit memory?
- skin conductance response regardless of explicit recall of a classmates face
- 3, 5 and adult year olds were given the incomplete picture test, then again 3 months later where they were give alongside controls and those that are out off focus
- only the 5 yr olds and adults had explicit memory of doing the task
- but all three groups had implicit memory of the event
what are the three main problems with nootropic studies?
- most tests done on animals or those with memory impairments
- tends of be of low quality p few participants, low controls
- typically a few positive findings, which tend to be hard to replicate or are small in effect size
