CHAPTER 13: THE BIOLOGY OF LEARNING AND MEMORY

Learning, Memory, Amnesia, And Brain Functioning

A. Classical Conditioning: After repeated presentations of a conditioned stimulus (CS), which initially elicits no response with an unconditioned stimulus (UCS), which automatically elicits an unconditioned response (UCR), the subject begins responding to the CS in a way similar to the UCS.

B. Operant Conditioning: Behavior is followed by a reinforcement (which increases the future probability of a response) or punishment (suppresses the frequency of a response).

C. Engram: Physical representation of learning.

D. Karl Lashley's work on learning after cortical lesions led him to propose two principles about the nervous system:

1. Equipotentiality: All parts of the cortex contribute equally to complex behaviors like learning; any part of the cortex can substitute for any other.

2. Mass action: The cortex works as a whole, and the more cortex the better.

E. Karl Lashley believed that the cerebral cortex was the best place to search for an engram, but years later Richard F. Thompson located an engram of memory in the cerebellum.

F. Lateral interpositus nucleus (LIP): Damage to this area of the cerebellum leads to permanent loss of a classically conditioned eyeblink response in rabbits.

G. Types of memory and amnesia

I . Short-term memory: Memory of events that have just occurred.

2. Long-term memory: Memory of events from previous times.

3. Donald Hebb theorized that any memory that stayed in short-term storage long enough would be gradually consolidated (strengthened) into a longterm memory. Meaningful and emotional information are more likely to be consolidated than other information.

4. Working memory: Temporary storage of memories to which one is attending at the moment. Working memory has three components:

• Phonological loop: Process which stores auditory information (including words).

• Visuospatial scratchpad: Stores visual information.

• Central executive: Directs attention toward one stimulus or another and determines what information will be stored in working memory. The ability to shift attention between one task and another appears dependent on the prefrontal cortex.

5. Delayed-response task: Memory task in which a subject is given a signal to which it must give a learned response after a delay. A common test for working memory.

H. The Hippocampus and Amnesia

1. Amnesia: Memory loss. Damage to the hippocampus produces a powerful kind of amnesia.

2. Patient H. M. had his hippocampus and surrounding brain tissue removed from both hemispheres to treat his severe epilepsy in 1953. However, he suffered moderate retrograde amnesia (loss of memory for events that occurred shortly before brain damage) and severe anterograde amnesia (loss of long-term memories for events that happened after brain damage) as a result of the bilateral hippocampal removal.

3. H. M. lost his declarative memory (the ability to state a memory in words) but retained his procedural memory (development of motor skills).

4. H. M. also has better implicit memory (influence of a recent experience on behavior, even if one does not realize that he or she is using memory at all) than explicit memory (deliberate recall of information that one recognizes as a memory)

5. Delayed matching-to-sample task: Task used to measure declarative memory in animals. In this procedure animals see an object (the sample) and after a delay get a choice between two objects, in which it must choose the one that matches the sample.

6. Delayed nonmatching-to-sample task: Similar to the above task except the animal must choose the one that differs from the sample.

7. Hippocampal damage impairs performance on both delayed matching-tosample and delayed nonmatching-to-sample tasks.

8. Radial Maze: Maze with eight or more arms used to test spatial memory in animals. Damage to the hippocampus impairs performance on this task.

9. Morris search task: Procedure where an animal has to find a hidden platform usually under murky water. This procedure is used to task spatial memory in animals and like the radial maze performance is negatively impacted by hippocampal damage.

10. Configural Learning: Procedure where the meaning of a stimulus depends on what other stimuli are paired with it. Early researchers believed that the hippocampus was necessary for this type of leaming because damage to the hippocampus impaired performance. However later researchers have argued that this type of task is not unique to the hippocampus. The impairment of performance after hippocampal damage is believed now to be due to the complexity of the task not the type of leaming.

1. Korsakoff's syndrome or Wemicke-Korsakoff's syndrome: Brain damage caused by prolonged thiamine deficiency (this disorder is most commonly seen in chronic alcoholics). Thiamine deficiency often leads to brain cell loss in the mamillary bodies of the hypothalamus and the dorsomedial nucleus of the thalamus, which projects to the prefrontal cortex. Korsakoff s patients have both anterograde and retrograde amnesia.

1. Priming: Type of implicit memory. Phenomenon that seeing or hearing words temporarily increases one's probability of using them. Like H. M, people with Korsakoff's syndrome have better implicit than explicit memory.

2. Confabulation: Making up an answer to a question and accepting the invented answer as if it were true (a common symptom of Korsakoff s syndrome).

J. Alzheimer's disease: A dementia which becomes more prevalent with advancing age. Symptoms include short-term and long-term memory loss, confusion, restlessness, hallucinations, and disturbances of eating and sleeping.

1. People with Alzheimer's disease have better procedural than declarative memory and better implicit than explicit memory.

2. People with Down syndrome (a type of mental retardation) usually get Alzheimer's disease if they survive into middle age.

3. Abnormal genes located on several different chromosomes can lead to an accumulation of amyloid deposits in the brain. The amyloid precursor protein, a large protein that is cleaved to form AP40 in normal cells but in Alzheimer's disease it is cleaved into a slighter larger protein amyloid beta protein 42 (AP42). Deposits of amyloid cause neuronal degeneration in the brain, and the dying axons and dendrites form plaques while the dying cell bodies form tangles in many areas of the cerebral cortex and hippocampus, as well as other brain areas.

K. Infant amnesia: Tendency for adults to be able to remember few memories prior to age 4 (this phenomenon may be due to an immature hippocampus).

II. Storing Information In The Nervous System

A. Hebbian synapse: A synapse that increases in effectiveness because of simultaneous activity in the presynaptic and postsynaptic neurons.

B. Aplysia as an Experimental Animal

1 . Aplysia is a marine invertebrate often used for physiological studies of leaming. Aplysia has fewer neurons than any vertebrate, and many are large and easy to study. Habituation: A decrease in response to a stimulus that is presented repeatedly and accompanied by no change in other stimuli.

2. Habituation in Aplysia reflects a decrease in neurotransmission between the sensory neuron and a motor neuron.

3. Sensitization: Becoming overresponsive to a mild stimulus after an intense stimulus has been presented.

4. Sensitization in Aplysia depends on the release of serotonin by a facilitating interneuron onto the synapses of many presynaptic sensory neurons; this process ultimately blocks potassium channels and thereby prolongs the release of transmitter from that neuron.

C. Long-Term Potentiation in Mammals

1. Long-term potentiation (LTP): Increased responsiveness to axonal input as a result of a previous period of rapidly repeated stimulation. UP has three properties that make it an attractive candidate for the cellular basis of learning and memory:

• Specificity: Only activated synapses become strengthened.

• Cooperativity: Nearly simultaneous stimulation by two or more axons produces LTP; stimulation by just one axon produces it weakly.

• Associativity: Pairing a weak input with a strong input enhances later response to the weak input.

2. Long-term depression (LTD): A prolonged decrease in response to a synaptic input that has been repeatedly paired with some other input, generally at a low frequency that occurs in the cerebellum and hippocampus.

3. All known cases of LTP depend on changes at glutamate receptors, especially the NMDA and AMPA type of glutamate receptors.

4. Usually glutamate produces neither excitatory nor inhibitory effects at NMDA receptors because magnesium blocks ion channels located on this receptor.

5. About the only way to activate NMDA receptors is first to stimulate nearby AMPA glutamate receptors repeatedly, thereby depolarizing the dendrite. Depolarization repels the magnesium ions and allows glutamate to open NMDA channels so that sodium and calcium ions can enter the cell.

6. Calcium ions induce the expression of otherwise inactive genes that produce proteins that alter the activities of more than a hundred other known chemicals within the dendrites and increase the future responsiveness of the receptors to glutamate.

7. Calcium enhances the responsiveness to glutamate by activating a protein called CaMKII leading to the following effects:

• The structure of the AMPA receptors changes, becoming more sensitive to glutamate.

• Some NMDA receptors change into AMPA receptors.

The dendrite may build more AMPA receptors or move them into a

better position.

The dendrite may make more branches, thus forming additional

synapses with the same axon.

8. Once LTP has been established, it no longer depends on NMDA synapses. Drugs that block NMDA prevent the establishment of LTP, but they do not interfere with the maintenance of LTP.