Learning, Memory and Amnesia

Cil FloresRegina Munoz

Kim Ocana

Monkeys with bilateral medial temporal lobectomies have major problems forming long-term memories for objects encountered in the delayed nonmatching-to-sample test.

Monkey model of object-recognition amnesia

Intact , well-trained monkeys performed correctly on about 90% of delayed nonmatching-to-sample trials when the retention intervals were a few minutes or less.

In contrast, monkeys with bilateral medial temporal lobe lesions had major object-recognition deficits.

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Medial temporal lobe lesionsNormal controls

The development of the delayed nonmatching-to-sample test for monkeys provided a means of testing the assumptions that the amnesia resulting from medial temporal lobe damage is entirely the consequence of hippocampal damage.

Aspiration lesions of the hippocampus in

monkeys and rats. Because of

differences in the size and location of the

hippocampus in monkeys and in rats,

hippocampectomy typically involves the

removal of large amounts of rhinal

cortex in monkeys, but not in rats.

Mumby box David Mumby Delayed nonmatching-to-sample test for rats It was assumed that rats could not perform a task

as complex as that required for the delayed nonmatching-to-sample test.

Combined bilateral lesions of rats’ hippocampus, amgdala, & rhinal cortex produce major retention deficits at all but the shortest retention intervals.

Hippocampal lesions consistently disrupt the performance of tasks that involve the memory for spatial location.

Morris water maze test◦ Rats with hippocampal lesions learn the task with

great difficulty. Radial arm maze test

◦ Intact rats readily learn to visit only those that contain food, without visiting the same arm more than once each day.

The Hippocampus and Memory for Spatial Location

Radial arm maze test◦ Reference memory-memory for the general

principles and skills that are required to perform a task

◦ Ability to visit only the baited arms of the radial arm maze.

◦ Working memory-temporary memory that is necessary for the successful performance of a task on which one is currently working.

◦ Ability to refrain from visiting an arm more than once in a given day

◦ Rats with hippocampal lesions display major deficits on both ref. & working memory.

Place cells◦ Neurons that respond only when a subject is in

specific locations.◦ By placing a rat in an ambiguous situation in a

familiar test environment, it is possible to determine whether 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

Hippocampal Place Cells

Species of birds that remember where they store seeds have larger hippocampuses than birds that do not store seeds, supporting the idea that hippocampus is important for spatial memory in many, if not all, species.

Comparative Studies of the Hippocampus and Spatial Memory

Experiment with humans in virtual-reality towns (show activity in hippocampus using positron emission tomography, PET) and with taxi drivers (bigger hippocampuses measured with magnetic resonance imaging, MRI) also support this idea.

Cognitive map theory◦ O’Keefe and Nadel◦ There are several systems in the brain that

specializes in the memory for different kinds of information, and the specific function of the hippocampus is the storage of memories for spatial location.

Theories of Hippocampal Function

Brown and AggletonTheory of the role of hippocampus in object

recognition that emphasizes its relation to the perirhinal cortex.

◦ Perirheral cortex, not the hippocampus, plays a key role in most object-recognition tasks.

Configural association memory◦ Based on the premise that spatial memory is one

specific manifestation of the hippocampus’s more general function.

◦ Hippocampus plays a role in the retention of the behavioral significance of combinations of stimuli, but not of individual stimuli.

Inferotemporal Cortex◦ The cortex of the inferior temporal lobe◦ Involved in the perception of objects, it is thought

to participate, in concert with perirhinal cortex, in storing memories of visual paterns.

Where are Memories Stored?

Amygdala ◦ Plays a role in memory for experiences with

emotional significance.◦ Rats with amygdalar lesions, unlike intact rats, do

not respond with fear to a neutral stimulus that has been repeatedly followed y electric foot shocks.

Prefrontal Cortex◦ The area of frontal cortex anterior to motor cortex◦ Are not grossly amnesic; they often display no

deficits at all on conventional tests of memory.Two memory abilities that are often lost by patients

with large prefrontal lesion deficit in memory for the temporal order of

events, even when they remember the events themselves

Deficits in working memory- the ability to maintain relevant memories while a task is being completed.

Cerebellum ◦ Thought to participate in the storage of memories

of learned sensorimotor skills through its various neuroplastic mechanisms

Striatum◦ Thought to store memories for consistent

relationships between stimuli and responses- the type of memories that develop incremental over many trials.

What is happening within the brain structures involved in memory?

The efficiency of synaptic transmission were the basis of long-term memory- Hebb

Long-Term Potentiation (LTP) - synapses are effectively made stronger by repeated stimulation

Synaptic Mechanism of learning and memory

Hebb hypothesized that consistent with the synaptic changes are the neural basis of learning and memory

LTP can last for many weeks after multiple stimulations

It is developed only if the firing of presynaptic neuron is followed by the firing of the postsynaptic neuron.

Hebb’s Postulate for learning- The Co-occurrence is necessary for learning and memory

Long-Term Potentiation (LTP)

The idea that LTP is related to the neural mechanisms of learning and memory has some several observations:

(1) Elicited by levels of stimulation that mimic normal neural activity

(2) LTP effects greatest in brain areas involved in learning and memory

(3)  Learning can produce LTP-like changes(4) Drugs that impact learning often have

parallel effects on LTP

Long-Term Potentiation (LTP)

All of the evidence is indirect that supports a role of LTP in learning and Memory

Has three part process:1. Induction (learning), 2. maintenance (memory) and3. expression (recall)

Long-Term Potentiation (LTP)

Usually studied at synapses at which NMDA receptor is prominent.

NMDA receptor is a receptor for glutamate which is the main excitatory neurotransmitter of the brain.

NMDA receptors do not respond maximally unless glutamate binds and the neuron is already depolarized

Calcium channels do not open fully unless both conditions are met

Induction of LTP: Learning

Learning Calcium influx only occurs if there is the co-occurrence that is needed for LTP, leading to the binding of glutamate at an NMDA receptor that is already depolarized

Calcium influx may activate protein kinases that induces changes causing LTP

Induction of LTP: Learning

The maintenance and expression of LTP involve changes in both presynaptic and postsynaptic neurons.

Only those synapses that were depolarized before high-frequency stimulation were involved in LTP

The maintenance of LTP involves structural changes which depend on protein synthesis

Maintenance and Expression of LTP: Storage and Recall

The discovery of structural changes in neurons following the induction of LTP stimulated a search for a mechanism by which neuron’s activity could change its structure which led to the discovery of transcription factors.

Nitric oxide synthesized in postsynaptic neurons in response to calcium influx may diffuse back to presynaptic neurons Structural changes are now a well-established consequence of LTP

Maintenance and Expression of LTP: Storage and Recall