Chapter 13. Biology of Learning and Memory
Essay questions:
1. Define anterograde and retrograde amnesia, explicit, implicit, declarative, procedural, semantic, and episodic memories
2. Describe the locations of brain damage and memory deficits of the case of H.M., Korsakoff's syndrome, and Alzheimer's patients
3. Describe the neural mechanisms of habituation and sensitization in aplysia
4. Describe the procedures of LTP production and the neural mechanisms of LTP
5. Describe the neural circuit mediating the nictating-membrane conditioning (eyelid response)
Chapter 13. Biology of Learning and Memory
1. Brain damage and human amnesia
1.1. Types of amnesia and memory
(1). Anterograde amnesia: loss of memory for events occurring after the amnesia-inducing event, such as, car accident, stroke
Ex: the person can not learn his new home address
(2). Retrograde amnesia: loss of memory for information learned before the amnesia-inducing event
Ex: who was the US President before President Bush
(3). Explicit memory: memories result from the deliberate effort to remember, recall, or recognition
Ex: how many States are in U.S.A. SAT test, Essay questions
(4). Implicit memory: memories acquired without conscious recall or recognition
Ex: when you are reading a newspaper and watching TV, later you can recall some words from TV programs
(5). Declarative memory: memory can be stated in words
(6). Procedural memory: motor skills learned through practice
(7). Semantic memory: memory for basic factorial knowledge about the world
(8). Episodic memory: memory for one's personal past experience.
It stores life events (or episodes) day after day, year after year.
Note: I wish I can erase bad memories in my brain
My memory problem is renting same movie
Benefits: I enjoy watching exciting movies (Like "True Lie")
Disadvantages: wasting money
1.2. The case of H.M. - with hippocampal damage
(1). The location of brain damages
The removal of medial portions of both temporal lobes, including most of the hippocampus, amygdala, and adjacent cortex for treating severe epilepsy
(See Transparency Overhead 59)
(2). Memory deficits
1). Moderate retrograde amnesia for events of the 1-3 years before the surgery and normal memory for remote events
2). Severe anterograde amnesia: he can not form long-term memories for events that occurred after his surgery, for example, he had no memory of his new home, new doctor, new friends, new job
3). Explicit memory deficits
a. Digit span + 1 test: after 25 trials with the same series of digits, he could do only 7 digits. Normal people can do 18 digits.
How to do it? Repeat the digits in the same order
Ex: 123, 3245, 56279, 786523, 8902154
b. Matching-to-sample tests
See Transparency Overhead Fig. )
He could not retain the non rehearsable items (various ellipses) for more than 5 seconds; control subjects retained all items perfectly
4). Intact procedural memory
See Transparency Overhead (Fig. 14.8)
He displayed substantial savings with no conscious recall of the drawing practice
1.3. Korsakoff's syndrome
(1). The location of the brain damages
See Transparency Overhead
The dorsomedial nucleus of the thalamus (which projects to the prefrontal cortex) and the mammillary bodies (part of the hypothalamus)
(2). The cause of the Korsakoff's syndrome: thiamine (VB1) deficiency.
Brain uses glucose as its main fuel
Thiamine helps brain to metabolize glucose
Alcoholics intake very little thiamine food (because they don't eat much food)
Thiamine deficiency leads to a loss of neurons through the brain (mainly in dorsomedial nucleus of the thalamus and mammillary bodies). The whole brain weight reduces
(3). The memory deficits
1). Retrograde amnesia (varying degree): last 15 years before drinking
2). Anterograde amnesia (varying degree): difficult to define the date of brain damage
3). Impaired memory of when and where something happened
Ex: when and where and what did you have your breakfast
4). Normal implicit memory
See Transparency Overhead (Fig. 14.6)
Korsakoff's patients often show signs of implicit memory without explicit memory
Two sets of weights were tested by subjects. If the first set of weights were light, they gave the second set of weights higher ratings (1-9 scales)
5). Normal procedural memory (driving a car)
1.4. Alzheimer's disease
(1). Statistics: 5% of people at 65-74 and 50% of at 85 suffer from Alzheimer's disease (President Reagan)
(2). The locations of brain damages
Neural degeneration in the frontal and temporal cortex, hippocampus, and basal forebrain due to amyloid protein deposits and massive reduction in cholinergic neurons
Less acetylcholine in the hippocampus and cortex
Lss choline acetylcholinetransferase (the enzyme that stimulates the synthesis of acetylcholine)
(3). Memory deficits
1). Anterograde amnesia (varying degree): difficult to learn new information such as names, phone number, appointments
2). Retrograde amnesia (varying degree): fail to remember the most basic information, such as face of a relative
3). Loss of explicit memory
4). Loss of certain implicit memory tasks
5). Better procedural than declarative memory
(4). Causes: not clear, suggestion: genetics
1). Down sydrome patients have an extra copy of chromosome 21 (usually two copies), they often develop alzheimer's disease after 40 years old
2). Chromosome 1 and 14 are involved in early-onst patients and chromosome 19 are involved in late-onset patients
(5). Treatment: not effective
Embryo gene therapy: by adding good genes to embryo cells
1.5. Brain and memory in young and old
(1). Infant amnesia
The phenomenon that most of us can not remember events happened before 4 years old
Why? hippocampus is not fully matured
(2). Old people amnesia
Hippocampus and related structures are deteriorating
Prefrontal cortex deteriorates in old people
(3). Motion sickness susceptibility
Young kids (0-3) never sick
12-18 most sensitive
Over 70 rarely sick
Why? New theory
2. Memory consolidation
2.1. Definition of consolidation: a memory is transferred from a short-term mode of storage to a long-term mode of storage
Short-term memory: information are retained in the memory for temporary use, then can not be retrieved
Long-term memory: a relatively permanent memory in which information is stored for use at a later time
一，二，四，三，五，六，七，八，九，十，百，千，万，亿，兆，二十，
三十，五百，九百，二千，四千，八万，六亿，七兆三亿四万二千六百五十一
口，人，天，火，日，月，古，胡，木，林，森，山，支，岐，胡森岐
2.2. Head-trauma interferes with consolidation
(1). Human studies
1). Closed-head injuries, such as cerebral concussion and contusion which both produce retrograde and anterograde amnesia.
Note: shaking infants causes head injuries
Blow to the head
period of period of period of recovering
retrograde coma anterograde with permanent
memory memory memory loss
Ex: victim of car accident can not remember what happen before and after the accident
2). Electroconvulsive shock (ECS): treating depression
Depressed patients have plans to kill themselves. After ECS, they forget the plan, ECS works well
(2). Animal studies: passive-avoidance learning
See Transparency Overhead (Fig. 14.10)
Procedures: a rat was placed on the wooden platform above a metal form for few seconds
When the feet of the rat contacts metal floor, the rat received a shock
After a while, the rat was put on the wooden platform, the rat will not step down on the metal floor. This is called passive-avoidance learning
Results: ECS can erase the memory of the foot shock
If the rat receives ECS through a head, when placed on the platform on a later day, the rat stepped down as quickly as rats that had never received a foot shock
2.3. Chemical enhancement of long-term memory
Increased level of epinephrine enhances consolidation of a memory.
However, excessive epinephrine has no effect
Explanation: epinephrine promotes the conversion of glycogen to glucose
Brain has more glucose to use
High glucose facilitates memory consolidation
3. Animal studies in brain damage and memory
3.1. Damage to the hippocampus in rats
See Transparency Overhead (Fig. 14.11)
(1). Procedures: a rat is placed in the center of eight arms
Some of arms have a bit of food at the end
After enough training trials, the rat may learn to go down each correct arm once without mistakes
(2). Results: rats with damage to the hippocampus will always forget to enter the correct arm for food
3.2. Damage to the hippocampus in primates
See Transparency Overhead 60
Delayed non matching-to-sample task
(1). Procedures:
1). A sample object A is presented
2). The monkey moves the object A to obtain food
3). A delay
4). The object A and another unfamiliar object B are presented
5). The correct choice is select the object B to obtain food
(2). Results:
Monkeys with hippocampal damage make numerous errors
(3). Hypothesis:
Hippocampus is a temporapy memory store.
Hippocampus acts as a map of where memories are stored in the cerebral cortex.
3.3. Damages to the prefrontal cortex
(1). If the damage is in a dorsal area called the principle sulcus, monkey had trouble to perform the delay matching-to-sample task
(2). If the damage is in a more ventral area, they will develop Perseveration patterns
That is the monkey chooses a same object repeatedly even though the choice is wrong
Note: Humans with prefrontal damage are impaired on a delayed alteration task
See Transparency Overhead 49 and Fig 14.14
1). A person first sort cards into stacks according to the one rule (for example, by shape)
2). Then reshuffle them and sort by a different rule (ex: color or number)
3). People with prefrontal damage can follow the first rule, but they have great trouble shifting to a new rule
4. Learning studies in invertebrate aplysia
Scientists believe that studying simple forms of learning in simple circuits is likely to reveal the fundamental principles of the neural basis of learning in complex system and that these principles would be discovered by studying complex system directly
4.1. The aplysia gill-withdrawal reflex circuit
See Transparency Overhead 118, 119
Aplysia is a simple marine snail; it depends on its life oozing along the ocean floor eating seaweed and expelling excess sea water and waste through a small fleshy sprout called siphon (siphon = mouth + anus)
If the siphon is touched, the siphon and gills of aplysia are immediately drawn up under a protective mantle
This is the aplysia gill-withdrawal reflex
The reflex is mediated by 24 sensory neurons in the skin of the siphon, a few small interneurons and 6 motor neurons that are responsible for gill and siphon retraction
4.2. Habituation in aplysia
(1). Definition: Habituation is a decrease in response to a stimulus following repeated presentation of the stimulus
(2). Procedures:
See Transparency Overhead 120 and Procedures
1). Repeatedly touch the siphon of aplysia for 10 minutes
2). Then waits for 10 minutes, touch the siphon again
3). Sensory neurons generate action potentials which reach the terminal buttons (no reduction in the number of APs)
4). The terminal buttons release less neurotransmitters into the synapse
5). As a result, motor neurons generate fewer action potentials
6). Fewer contractions of gill-retractor muscles
(3). Neural mechanisms: habituation in aplysia is mediated by a decrease in the amount of neurotransmitters released by the presynaptic sensory neuron terminals in response to their own action potential
4.3. Sensitization in aplysia
(1). Definition: Sensitization is an increase in the strength of a response to a stimulus
(2). Procedures:
See Transparency Overhead 120, 69, Procedures
1). A strong electric shock applies to the tail of aplysia
2). A facilitating interneuron is excited
3). The facilitating interneuron terminal buttons release 5HT on to the synapses of sensory neurons
4). 5HT induces the sensory neurons to release more neurotransmitters when a siphon is touched
5). As a result, motor neurons generate more action potentials and gill-tractor muscles increase their contractions
(3). Neural mechanisms: Sensitization in aplysia is mediated by an increase in the amount of neurotransmitters released by the presynaptic sensory neuron terminals in response to their own action potentials
5. Long-term potentiation (LTP)
(1). Procedures of LTP production:
See Transparency Overhead T62 (Figure 15-15), 121, 122
1). The presynaptic neurons receive a few seconds of intense high-frequency stimulation
2). This causes the response of the postsynaptic neurons to subsequent low-intensity stimulation of the presynaptic neurons to be heightened for hours, days, or weeks
3). LTP is often studied in the hippocampal slice preparation and cortex of the mammalian brain
4). LTP is recorded from the gradual-cell layer of the hippocampal dentate gyrus following an intense high- frequency perforant path stimulation
(2). Neural mechanisms:
See Transparency Overhead 123, 124, 125, 126, 66, 67, 68
1). Glutamate is the main excitatory neurotransmitter in the hippocampus
2). LTP depends on changes at glutamate receptors, the NMDA and AMPA receptors
3). Usually glutamate produces neither excitatory nor inhibitory effects at NMDA receptors because magnesium blocks ion channels located on this receptor
4). The only way to activate NMDA receptors is first to repeatedly stimulate nearby AMPA glutamate receptors, thereby depolarizing the dendrites
5). 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 increases of the future responsiveness of these glutamate receptors to glutamate
(3). Conclusion:
1). LTP is a mechanism of long-term memory
2). LTP is a contributor for vertebrate learning
3). Drugs that block NMDA receptors erase the long-term memory
6. Learning and memory in eyelid (the nictitating-membrane) response circuit of the rabbit
(1). Procedures of conditioning of eyelid response:
See Transparency Overhead Figure 16.2 and Procedures
1). A tone (conditional stimulus) is turned on
2). 250 ms later, a puff of air to the eye (the unconditional stimulus) is presented
3). The tone and air puff terminate simultaneously
4). When the air puff is administered, an inner eyelid called nictitating-membrane slides over the eye to protect it
5). With repeated trials, eyelid (the nictitating-membrane) responses can be elicited by the tone only (conditional responses)
6). Thus, the association between the tone conditional stimulus and the puff unconditional stimulus is formed
Note: Nictate = nictitate
Nictation = nictitation
(2). The neural circuit for unconditional response to unconditional stimulus
The air puff to the eye (US)
trigeminal nerve
abducens nucleus
nictitating membrane responses (unconditional responses)
(3). The neural circuit mediating the nictating-membrane conditioning (eyelid response)
The air puff to eye (US) tone input (CS)
Trigeminal nerve pontine nuclei
interpositus nucleus in cerebellum
(association between US and CS is formed)
abducens nucleus
nictitating membrane responses
Thus, after association is formed the tone alone will activate the circuit and cause nictitating-membrane withdrawal responses
7. The biochemistry of learning and memory
7.1. Influence of protein synthesis on learning and memory
Drugs that inhibit protein synthesis impair the long-term storage of memory
Ex: anisomycin: a drug that inhibits protein synthesis blocks a rat's memory of the location of shock
7.2. Acetylcholine synapses and memory
(1). Alzheimer's patients show a striking decline in brain acetylcholine content
(2). Scopolamine: a drug that blocks acetylcholine induces deficiencies on a variety of memory tasks
(3). Physostigmine: a drug that increase acetylcholine effects at synapses improves memory
7.3. Norepinephrine and dopamine synapses in the prefrontal cortex are major contributors to memory
Drugs that enhance the activity of norepinephrine-releasing neurons improve memory