Learning and Memory
Functional Perspectives on Memory
There are several kinds of memory and learning.
Memory has temporal stages: short, intermediate, and long.
Successive processes capture, store, and retrieve information in the brain.
Different brain regions process different aspects of memory.
Neural Mechanisms of Memory
Memory storage requires neuronal remodeling.
Invertebrate nervous systems show plasticity.
Synaptic plasticity can be measured in simple hippocampal circuits.
Some simple learning relies on circuits in the mammalian cerebellum.
In the adult brain, newly born neurons may aid learning.
Learning and memory change as we age.
Several Kinds of Memory and Learning
Learning is the process of acquiring new information.
Memory:
The ability to store and retrieve information.
The specific information stored in the brain.
Patient H.M. (Henry Molaison) suffered from severe epilepsy.
Surgery removed the anterior temporal lobes on both sides, including the amygdala, hippocampus, and some cortex.
Retrograde amnesia: Loss of memories formed before the onset of amnesia.
Not uncommon after brain trauma.
Anterograde amnesia: Inability to form memories after the onset of amnesia.
H.M. had normal short-term memory but severe anterograde amnesia.
Damage to the hippocampus can produce memory deficits.
H.M. could improve motor skills but couldn't remember performing them (couldn't recall tasks verbally).
His memory deficit was confined to describing the tasks he performed.
Two kinds of memory:
Declarative memory: Deals with what—facts and information acquired through learning that can be stated or described.
Things we are aware of that are learned.
Nondeclarative (procedural) memory: Deals with how—shown by performance rather than conscious recollection.
Patient N.A. has amnesia due to accidental damage to the left dorsal thalamus, bilateral damage to the mammillary bodies (limbic structures in the hypothalamus), and probable damage to the mammillothalamic tract.
Like Henry Molaison, he has short-term memory but cannot form declarative long-term memories.
Korsakoff’s syndrome: Memory deficiency caused by lack of thiamine—seen in chronic alcoholism.
Patients often confabulate—fill in a gap in memory with a falsification which they accept as true.
Brain damage occurs in mammillary bodies and dorsomedial thalamus, similar to N.A., and to the basal frontal cortex.
Two subtypes of declarative memory:
Semantic memory—generalized memory.
Episodic memory—detailed autobiographical memory.
Patient K.C. cannot retrieve personal (episodic) memory due to accidental damage to the cortex and severe shrinkage of the hippocampus and parahippocampal cortex; his semantic memory is good.
Three subtypes of nondeclarative memory:
Skill learning—learning to perform a task requiring motor coordination.
Priming—repetition priming—a change in stimulus processing due to prior exposure to the stimulus.
Conditioning—the association of two stimuli or of a stimulus and a response.
Memory Temporal Stages
Iconic memories are the briefest memories and store sensory impressions that only last a few seconds.
Short-term memories (STMs) usually last only for up to 30 seconds or throughout rehearsal.
Short-term memory is also known as working memory.
Working memory can be subdivided into three components, all supervised by an executive control module:
Phonological loop—contains auditory information.
Visuospatial sketch pad—holds visual impressions.
Episodic buffer—contains more integrated, sensory information.
An intermediate-term memory (ITM) outlasts a STM, but is not permanent.
Long-term memories (LTMs) last for days to years.
Mechanisms differ for STM and LTM storage but are similar across species.
The primacy effect is the higher performance for items at the beginning of a list (LTM).
The recency effect shows better performance for the items at the end of a list (STM).
Long-term memory has a large capacity.
Information can also be forgotten or recalled inaccurately.
Successive Processes
A functional memory system incorporates three aspects:
Encoding—sensory information is passed into short-term memory.
Consolidation—short-term memory information is transferred into long-term storage.
Retrieval—stored information is used.
Multiple brain regions are involved in encoding, as shown by fMRI.
For recalling pictures, the right prefrontal cortex and parahippocampal cortex in both hemispheres are activated.
For recalling words, the left prefrontal cortex and the left parahippocampal cortex are activated.
The prefrontal cortex and parahippocampal cortex are important for consolidation.
These mechanisms reflect hemispheric specializations (left hemisphere for language and right hemisphere for spatial ability).
The engram, or memory trace, is the physical record of a learning experience and can be affected by other events before or after.
Each time a memory trace is activated and recalled, it is subject to changes.
Consolidation of memory involves the hippocampus, but the hippocampal system does not store long-term memory.
LTM storage occurs in the cortex, near where the memory was first processed and held in short-term memory.
In posttraumatic stress disorder (PTSD, characterized as reliving and being preoccupied by traumatic events), memories produce stress hormones that further reinforce the memory.
GABA, ACh, and opioid transmission can also enhance memory formation in animal models.
Treatments that can block chemicals acting on the basolateral amygdala may alter the effect of emotion on memories.
The process of retrieving information from LTM can cause memories to become unstable and susceptible to disruption or alteration.
Reconsolidation is the return of a memory trace to stable long-term storage after it’s temporarily volatile during recall.
Reconsolidation can distort memories.
Successive activations can deviate from original information.
New information during recall can also influence the memory trace.
Leading questions can lead to ‘remembering’ events that never happened.
‘Recovered memories’ and ‘guided imagery’ can have false information implanted into the recollection.
Different Brain Regions
Testing declarative memories in monkeys:
Delayed non-matching-to-sample task—a test of object recognition memory, where the subject must choose the object that was not seen previously.
Medial temporal lobe damage causes impairment on the delayed nonmatching-to-sample task.
The amygdala is not necessary for declarative memory tasks.
The hippocampus (in conjunction with the entorhinal, parahippocampal) and perirhinal cortices, is important for these tasks.
Imaging studies confirm the importance of medial temporal (hippocampal) and diencephalic regions in forming long-term memories.
Both are activated during encoding and retrieval, but long-term storage depends on the cortex.
Episodic and semantic memories are processed in different areas.
Episodic (autobiographical) memories cause greater activation of the right frontal and temporal lobes.
Early research indicated that animals form a cognitive map—a mental representation of spatial relationships.
Latent learning is when acquisition has taken place but has not been demonstrated in performance tasks.
Early work indicated that rats running mazes form a cognitive map; the hippocampus is crucial for spatial learning.
Place cells in the hippocampus become active when an animal is in or moving toward a particular location.
Grid cells fire when an animal crosses intersection points of an abstract grid.
Arrival at the perimeter of a spatial map is signaled by firing of entorhinal border cells.
The hippocampus is also important in spatial learning.
It contains place cells that become active when in, or moving toward, a particular location.
Place cells remap when a rodent is placed in a new environment.
Grid cells and border cells are neurons that fire when animal is at an intersection and at the perimeter of an abstract grid map, respectively.
In rats, place cells in the hippocampus are more active as the animal moves toward a particular location.
In monkeys, spatial view cells in the hippocampus respond to what the animal is looking at.
Comparisons of behaviors and brain anatomy show that increased demand for spatial memory results in increased hippocampal size (relative to the rest of the brain) in mammals and birds.
In food-storing species of birds, the hippocampus is larger but only if used to retrieve stored food.
Spatial memory and hippocampal size can change within the life span.
In some species, there can be sex differences in spatial memory, depending on behavior.
Polygynous male meadow voles travel further (to find females) and have a larger hippocampus than female meadow voles or males of monogamous pine voles.
Imaging studies help to understand learning and nondeclarative memory for different skills:
Sensorimotor skills, such as mirror-tracing.
Perceptual skills—learning to read mirror-reversed text.
Cognitive skills—planning and problem solving.
All three of these depend on functional basal ganglia; the motor cortex and cerebellum are also important for some skills.
Imaging studies of repetition priming show reduced bilateral activity in the occipitotemporal cortex, related to perceptual priming.
Perceptual priming reflects prior processing of the form of the stimulus.
Conceptual priming (priming based on word meaning) is associated with reduced activation of the left frontal cortex.
Imaging of conditioned responses can show changes in activity.
PET scans made during eye-blink tests show increased activity in several brain regions, but not all may be essential.
Patients with unilateral cerebellar damage can acquire the conditioned eye-blink response only on the intact side.
Different brain regions are involved with different attributes of working memories such as space, time, or sensory perception.
Memory tasks assess the contributions of each brain region.
The eight-arm radial maze is used to test spatial location memory.
Rats must recognize and enter an arm that they have entered recently to receive a reward.
Only lesions of the hippocampus produce a deficit in this predominantly spatial task.
In a memory test of motor behavior, the animal must remember whether it made a left or right turn previously.
If it turns the same way as before, it receives a reward.
Only animals with lesions to the caudate nucleus showed deficits.
Sensory perception can be measured by the object recognition task.
Rats must identify which stimulus in a pair is novel.
This task depends on the extrastriate cortex.
Interim summary of brain regions involved in learning and memory:
Many brain regions are involved.
Different forms of memory are mediated by at least partly different mechanisms and brain structures.
The same brain structure may be involved in many forms of learning.
Neural Mechanisms
Molecular, synaptic, and cellular events store information in the nervous system.
New learning and memory formation can involve new neurons, new synapses, or changes in synapses in response to biochemical signals.
Neuroplasticity (or neural plasticity) is the ability of neurons and neural circuits to be remodeled by experience or the environment.
Sherrington speculated that alterations in synapses were the basis for learning.
Synaptic changes can be measured physiologically, and may be presynaptic, postsynaptic, or both.
Changes include increased neurotransmitter release and/or a greater effect due to changes in neurotransmitter-receptor interactions.
Changes in the rate of inactivation of transmitter would also increase effects.
Inputs from other neurons might increase or decrease neurotransmitter release.
Structural changes at the synapse may provide long-term storage.
New synapses could form or some could be eliminated with training.
Training might also lead to synaptic reorganization.
Lab animals living in a complex environment demonstrated biochemical and anatomical brain changes from those living in simpler environments.
Three housing conditions:
Standard condition (SC)
Impoverished (or isolated) condition (IC)
Enriched condition (EC)
Animals housed in EC, compared to those in IC, developed:
heavier, thicker cortex;
enhanced cholinergic activity;
More dendritic branches (especially on basal dendrites near the cell body), with more dendritic spines suggesting more synapses.
Synaptic Plasticity
Long-term potentiation (LTP)—a stable and enduring increase in the effectiveness of synapses.
A weakening of synaptic efficacy—termed long-term depression—can also encode information.
Synapses in LTP behave like Hebbian synapses:
Tetanus drives repeated firing.
Postsynaptic targets fire repeatedly due to the stimulation.
Synapses are stronger than before.
LTP can be generated in conscious and freely behaving animals, in anesthetized animals, and in tissue slices and that LTP is evident in a variety of invertebrate and vertebrate species.
LTP can also last for weeks or more.
Superficially, LTP appears to have the hallmarks of a cellular mechanism of memory.
LTP occurs at several sites in the hippocampal formation—formed by the hippocampus, the dentate gyrus and the subiculum (also called subicular complex or hippocampal gyrus).
The hippocampus has regions called CA1, CA2, and CA3 (CA=Cornus Ammon which means Ammon’s Horn).
The CA1 region has two kinds of glutamate receptors:
NMDA receptors (after its selective ligand, N-methyl-D-aspartate)
AMPA receptors (which bind the glutamate agonist AMPA)
Glutamate first activates AMPA receptors.
NMDA receptors do not respond until enough AMPA receptors are stimulated, and the neuron is partially depolarized.
NMDA receptors at rest have a magnesium ion () block on their calcium () channels.
After partial depolarization, the block is removed, and the NMDA receptor allows to enter in response to glutamate.
The large influx activates certain protein kinases—enzymes that add phosphate groups to protein molecules.
One protein kinase is CaMKII (calcium-calmodulin kinase II) which affects AMPA receptors in several ways:
Causes more AMPA receptors to be produced and inserted in the postsynaptic membrane.
Moves existing nearby AMPA receptors into the active synapse.
Increases conductance of and ions in membrane-bound AMPA receptors.
These effects all increase the synaptic sensitivity to glutamate.
The activated protein kinases also trigger protein synthesis.
Kinases activate CREB—cAMP responsive element-binding protein.
CREB binds to cAMP responsive elements in DNA promoter regions.
CREB changes the transcription rate of genes.
The regulated genes then produce proteins that affect synaptic function and contribute to LTP.