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PSY-2 Ch13: Memory & Learning
- 1. Ch13: Memory & Learning ➔Types of Learning & Memory ➔Neural Mechanisms of Memory
- 2. TYPES OF LEARNING & MEMORY • LEARNING: the process of acquiring new information • MEMORY is: – the ability to store and retrieve information – the specific information stored in the brain
- 3. CASE STUDY: Patient H.M. • Epilepsy • Removal of anterior temporal lobe TYPES OF LEARNING & MEMORY HENRY MOLAISON
- 4. TYPES OF LEARNING & MEMORY • Types of Amnesia: – RETROGRADE: loss of info stored before the onset of amnesia – ANTEROGRADE: inability to store info after the onset of amnesia
- 5. TYPES OF LEARNING & MEMORY
- 6. TYPES OF LEARNING & MEMORY
- 7. TYPES OF LEARNING & MEMORY
- 8. TYPES OF LEARNING & MEMORY
- 9. TYPES OF LEARNING & MEMORY
- 10. TYPES OF LEARNING & MEMORY • DELAYED NON-MATCHING-TO-SAMPLE TASK: requires animals to declare what they remember
- 11. TYPES OF LEARNING & MEMORY • Patient N.A.: – Damage to the DORSOMEDIAL THALAMUS and MAMMILLARY BODIES – STM is intact, but cannot form new declarative LTMs
- 12. TYPES OF LEARNING & MEMORY • KORSAKOFF’S SYNDROME: – Memory deficiency caused by lack of thiamine – Damage to mammillary bodies, but not hippocampus
- 13. TYPES OF LEARNING & MEMORY • Patient K.C. – Damage to hippocampus and cortex – Anterograde amnesia – Loss of all personal memory of his past • Two subtypes of declarative memory: – SEMANTIC MEMORY: general knowledge of facts and info – EPISODIC MEMORY: autobiographical memory
- 14. TYPES OF LEARNING & MEMORY TYPES OF NONDECLARATIVE LTM • SKILL LEARNING: learning to perform a task through repetition – Basal ganglia • PRIMING: exposure to a stimulus facilitates later responses to similar stimuli – Cortex • ASSOCIATIVE LEARNING: association between two events – Cerebellum
- 15. TYPES OF LEARNING & MEMORY The 8-arm radial maze tests spatial location memory – Rats must recognize and enter a certain arm
- 16. TYPES OF LEARNING & MEMORY In a memory test of motor behavior – Rats must turn the same way as before to receive a reward
- 17. TYPES OF LEARNING & MEMORY Sensory perception: measured by the object recognition (non-matching-to-sample) task – Rats must identify which stimulus is novel
- 18. TYPES OF LEARNING & MEMORY
- 19. Ch13: Memory & Learning ➔Types of Learning & Memory ➔Neural Mechanisms of Memory
- 20. NEURAL MECHANISMS OF MEMORY NEUROPLASTICITY : ability of the NS to change in response to experience or environment 1. Increased synaptic strength
- 21. NEURAL MECHANISMS OF MEMORY NEUROPLASTICITY : ability of the NS to change in response to experience or environment 2. Interneuron Modulation
- 22. NEURAL MECHANISMS OF MEMORY NEUROPLASTICITY : ability of the NS to change in response to experience or environment 3. New Synapses Added
- 23. NEURAL MECHANISMS OF MEMORY NEUROPLASTICITY : ability of the NS to change in response to experience or environment 4. More active pathways take over
- 24. NEURAL MECHANISMS OF MEMORY Living in a complex environment = biochemical & anatomical brain changes
- 25. NEURAL MECHANISMS OF MEMORY Animals housed in the enriched condition developed: • Heavier, thicker cortex • Enhanced cholinergic activity • More dendritic branches and spines • Larger synapses • More neurons in the hippocampus • Enhanced recovery from brain damage
- 26. NEURAL MECHANISMS OF MEMORY • HABITUATION: a decrease in response to a repeated stimulus – Squirts of water on its siphon causes it to retract its gill – After repeated squirts, the animal retracts the gills less Eric Kandel
- 27. NEURAL MECHANISMS OF MEMORY • SHORT-TERM HABITUATION: caused by decreased NT release • Less NT = less gill retraction
- 28. NEURAL MECHANISMS OF MEMORY • LONG-TERM HABITUATION: habituation occurs faster each day; caused by fewer synapses • Fewer synapses = less gill retraction
- 29. NEURAL MECHANISMS OF MEMORY Researchers use the eye-blink reflex to study neural circuits in mammals
- 30. NEURAL MECHANISMS OF MEMORY Researchers use the eye-blink reflex to study neural circuits in mammals
- 31. NEURAL MECHANISMS OF MEMORY Researchers use the eye-blink reflex to study neural circuits in mammals
- 32. NEURAL MECHANISMS OF MEMORY • HEBBIAN SYNAPSES: – A synapse strengthens when it creates activation in the postsynaptic cell – Neurons act together to store memory traces D. O. Hebb
- 33. NEURAL MECHANISMS OF MEMORY • TETANUS: – An intense series of axon potentials from a presynaptic cell – Causes postsynaptic neurons to produce larger EPSPs • LONG-TERM POTENTIATION (LTP): an enduring increase in the effectiveness of synapses
- 34. NEURAL MECHANISMS OF MEMORY • LTP occurs at pathways in the hippocampal formation—formed by the hippocampus and the DENTATE GYRUS • The most-studied hippocampal LTP uses the transmitter GLUTAMATE and depends on NMDA RECEPTORS along with AMPA RECEPTORS
- 35. At low level activity: • GLU release activates only AMPA receptors • NMDA receptors at rest have a magnesium ion (Mg2+) block on their calcium (Ca2+) channels NEURAL MECHANISMS OF MEMORY
- 36. At higher levels of activity: • Enough AMPA receptors are stimulated to partially depolarize the membrane • With partial depolarization & GLU, the NMDA receptor is activated • Mg2+ block is removed, allowing Ca2+ to enter NEURAL MECHANISMS OF MEMORY
- 37. • Ca2+ activates enzymes in the postsynaptic cell, causing changes in AMPA receptors: – Existing ones move to the active synapse – Increased conductance of ions – More receptors are produced NEURAL MECHANISMS OF MEMORY
- 38. • Presynaptic changes in LTP: – Postsynaptic cell releases a RETROGRADE TRANSMITTER – Ensures that more GLU will be released, strengthens the synapse NEURAL MECHANISMS OF MEMORY
- 39. • The postsynaptic cell now has a stronger response • More NT is released and more AMPA receptors are present • Synapses without LTP will become weaker and fade away NEURAL MECHANISMS OF MEMORY
- 40. NEURAL MECHANISMS OF MEMORY Neurons that fire together wire together.
- 41. NEURAL MECHANISMS OF MEMORY • Evidence for LTP in the real world: – Correlational observations: time course of LTP is similar to that of memory formation – Somatic intervention experiments: • Drugs that block LTP also impair learning • Mice that overexpress NMDA receptors have enhanced LTP and better memory – Behavioral intervention experiments: training an animal in a memory task can induce LTP
Editor's Notes
- PART I Types of Learning and Memory There Are Several Kinds of Memory and Learning Different Forms of Nondeclarative Memory Involve Different Brain Regions Successive Processes Capture, Store, and Retrieve Information in the Brain
- Brain damage can impair learning and memory, and reveal different classes
- Researchers quickly zeroed in on the hippocampus as the potential source of H.M’s difficulty. Other patients who had nearby structures removed (amygdala, etc) DID NOT demonstrate memory impairment.
- As a young man, Patient H.M. had the hippocampus from both hemispheres surgically removed, with disastrous results. The surgeons did not remove the cerebellum but the loss of hippocampal inputs caused it to shrink as he aged. To understand how the hippocampus affects memory, we need to consider how the human mind uses and stores information. Let’s take a look at our current understanding of memory (info-processing).
- THREE STAGE MODEL OF MEMORY: ICONIC MEMORIES: are the briefest and store sensory impressions SHORT-TERM MEMORIES (STMs): usually last only for seconds, or throughout rehearsal aka working memory LONG-TERM MEMORIES (LTMs): last for days to years A functional memory system incorporates three processes: ENCODING: information entering sensory channels is passed into STM CONSOLIDATION: information in STM is transferred into LTM RETRIEVAL: memories stored in LTM are accessed and used A subset of the sensory information that enters iconic memory is encoded and placed into STM. If the information is rehearsed or used, it may be consolidated into LTM, lasting for minutes all the way up to a lifetime. When we probe a subject’s memory, she must retrieve it from LTM and place it into STM to perform a task, such as reporting the items in a list. At any stage of the process, information may be forgotten or lost. At first glance, H.M.’s situation seems simple. He lost the ability to build new LTMs (consolidate information). BUT! Check out the mirror drawing task
- Henry was given this mirror-tracing task to test motor skill. Although he never recognized the task, his performance progressively improved over successive days, demonstrating a type of LTM. There was another wrinkle as well… doctors tried to re-create H.M.’s symptoms by removing the hippocampus from lab animals, to see if it would destroy their ability to form LTMs.
- Once information is moved into LTM, it can be stored in multiple formats. In other words, there are many types of LTM. Two categories of memory: Declarative memory—facts and information acquired through learning that can be stated or described to answer “what” questions. These memories can be tested easily in humans because they can talk. H.M. was unable to form new declarative memories, indicating that the hippocampus is needed to form these memories, but that they must be stored elsewhere. Nondeclarative (procedural) memory—shown by performance rather than recollection, to answer “how” questions. Can be tested readily in other animals, as well as in humans. H.M. could form this type of memory, as when he learned the skill of mirror tracing.
- The monkey is initially presented with a sample object. When he moves the object, he finds a pellet of food underneath. After a delay (seconds to minutes long), the monkey is presented with the original object and another, new object. Over a series of trials, the monkey learns that food is present under the object that DIFFERS from the sample. The monkey DECLARES his memory of the key by not choosing it. Medial temporal lobe damage, similar to Henry’s, causes impairment on this task
- Patient N.A. received damage due to the insertion of a miniature sword through a nostril and into the brain. Profound anterograde amnesia ever since the accident, primarily for verbal material. Memory for earlier events is near normal, but can give little new information about events since his accident. The hippocampus itself is intact, but limbic system structures that connect to it are no damaged: dorsomedial thalamus and mammillary bodies. Their similar symptoms with damage in different regions suggests a larger memory network.
- Degenerative disease that affects similar areas of the brain as those injured in Patient N.A. Typically seen in folks who are severely addicted, receiving most of their calories from alcohol and therefore not receiving enough thiamine. Treatment with thiamine can prevent further deterioration but cannot reverse the damage. Often fail to recognize or show familiarity with items, even when presented repeatedly. Deny that anything is wrong. Confabulate to fill in the gaps with false information that they accept as true. The confabulation may be due to damage in the frontal cortex. Their similar symptoms with damage in different regions suggests a larger memory network.
- Damage occurred as a result of a motorcycle accident. Brain scans revealed extensive damage to the left frontoparietal cortex and the right parieto-occipital cortex, severe shrinking of the hippocampus. Anterograde amnesia – cannot form new declarative LTMs. Also shows the loss of all personal memories from his past. He can recognize family members and tell you his name, but he can’t remember any specific experiences with those people. K.C.s hippocampal damage accounts for his anterograde amnesia, but not for the loss of his autobiographical memory Brain-imaging studies show that semantic and episodic memories are processed and stored in different locations This also reveals an important distinction between two types of declarative memories. Semantic & Episodic. K.C. lost his episodic memories from the past.. But he still maintains most of his semantic knowledge.
- Confirming what we know from Patient K.C., brain imaging studies also demonstrate the difference between semantic and episodic declarative memories. Subjects listened to recordings of stories about themselves or about other people. When listening to a story about themselves, they showed great activation in the right frontal and temporal lobe regions. It seems as though these episodic memories are processed in different locations and stored in different parts of the cortex.
- Skill Learning: used for tasks such as the mirror tracing task, learning to ride a bike, etc. Regardless of the type of skill (perceptual, sensorimotor, cognitive), the basal ganglia seem to be involved. Basal Ganglia = group of forebrain nuclei, including the caudate nucleus, globus pallidus, & putamen. Found deep within the cerebral hemispheres. Crucial for skill learning, behaviors, habits, and rewards. Priming: example of semantic priming (seeing words in a list of crossword puzzles, and later completing a word stem with that word). Does not require declarative memory – H.M. shows priming.
- Early research indicated that animals form a cognitive map—a mental representation of a spatial relationship The hippocampus is important in spatial learning It contains place cells that become active when in, or moving toward, a particular location Tasks examine different attributes of memory, and lesions assess contributions of different brain regions In the study phase of each trial, the rate can choose any of the eight arms. In the test phase, doors block all but two arms: the arm entered in the study phase and one other. The rat obtains food only if it chooses the arm it entered in the study phase. Only rats with hippocampal lesions are impaired, relative to controls.
- In the first part of each trial, the rat is placed in the middle compartment on one side (2), and it finds food if it enters the compartment to either its right (1) or its left (3). In the second part of the trial, it is placed in the middle compartment on the other side (5) and it finds food only if it turns to the same side of its body as in the first part. Only rats with basal ganglia lesions are impaired, relative to controls.
- Sensory perception can be measured by the object recognition (non-matching-to-sample) task Rats must identify which stimulus in a pair is novel Cortical lesions produced impairments on this task In the study phase of each trial, the rat obtains food by displacing a sample object over a small food well (top). In the test phase (bottom), the rat chooses between two objects and obtains food only if it chooses the object that does NOT match the sample. Only rats with lesions of the extrastriate visual cortex are impaired, relative to controls.
- A summary of brain regions in learning and memory: Many regions of the brain are involved Different forms of memory rely on different brain mechanisms, which may include different regions The same brain structure can be involved in different forms of learning
- PART II Neural Mechanisms of Memory Memory Storage Requires Neuronal Remodeling Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits
- Molecular, synaptic, and cellular events store information in the nervous system New learning and memory formation involves changes in the strength of synapses in response to biochemical signals Memories can also require formation of new synapses or birth of new neurons Synaptic changes can be measured physiologically, and may be presynaptic, postsynaptic, or both: Increased neurotransmitter release Inactivation of the transmitter A greater effect due to changes in receptors Influence by other neurons Long-term memories may bring about structural changes: New synapses can form or old ones die back Training can bring about reorganization Several different changes can result in a more effective synapse. After Training 1: More NT is released from the axon terminal. OR After Training 2: Postsynaptic membrane becomes larger and/or more sensitive to NT. OR After Training 3: Synapse enlarges both pre- and postsynaptically.
- B. An interneuron modulates polarization of the axon terminal and causes the release of more NT molecules per nerve impulse.
- C. A neural circuit that is used more often increases the number of synaptic contacts.
- D. A more frequently used neural pathway takes over synaptic sites formerly occupied by a less active competitor. Survival of the fittest – more active pathways will take over less active pathways. How does this affect organisms? Brain can change dramatically in response to the environment. This IS plasticity.
- Three housing conditions: Standard condition (SC): animals are housed in small groups in standard lab cages. This is the typical environment for laboratory animals. Impoverished (or isolated) condition (IC): Animals are housed individually in standard lab cages. Enriched condition (or complex environment) (EC): Animals are housed in large social groups in special cages containing various toys and other interesting features. This condition provides enhanced opportunities for learning perceptual and motor skills, social learning, and so on.
- A. An enlarged photograph of a neuron is used to quantify branching either by counts of the number of branches of different orders… or by counts of the number of intersections with concentric rings. B. Analyzing basal dendrites revealed that rats kept for a month in enriched environments had more branches than did rats in other conditions. The cerebral effects of experience are seen to widely occur in the animal kingdom (from flies to philosophers). But how to study this in mammalian networks, involving billions of neurons arranged in vast networks? Find a simpler model!
- Invertebrate NSs show synaptic plasticity. It is difficult for us to study the physiology of learning, because the brains of mammals are incredibly complex, housing more than a billion synapses per cubic centimeter of tissue. One solution is to study very simple learning circuits in much simpler, animals, such as invertebrates. These species have relatively fewer neurons (hundreds to tens of thousands instead of billions). Aplysia has been a useful model. Eric Kandel won the Nobel Prize in 2000 for his research with this sea slug. Aplysia shows a very simple gill-withdrawal reflex. Stimulus such as a touch or a jet of water to the siphon causes the animal to retract its delicate gill. However, after repeated stimulation the animal shows habituation. It retracts the gill less. It has learned that the water poses no real danger.
- There are actually two different types of habituation taking place in the gill-withdrawal research on Aplysia. A: When the siphon is first stimulated by a squirt of water, Aplysia retracts its gill, protecting the gill in case the animal is under attack. This reflex is mediated by the sensory neurons synapsing directly upon the motoneurons that withdraw the gill. There are many sensory neurons and motoneurons, but only one of each is shown. If the siphon is squirted repeatedly over the course of an hour, the animal soon habituates to the stimulus. It no longer retracts its gill. This short-term habituation results because the sensory neurons release progressively less NT onto the motoneurons. Less NT = less retraction. We can also see longer term changes.
- If the siphon is squirted repeatedly over days, the animal habituates faster and faster each day and eventually shows almost no response. This long-term habituation is due to a retraction of some of the synaptic terminals from the sensory neurons onto the motoneurons. Lasts up to 3 weeks, then the changes fade away if the stimulus is no longer experienced
- An air puff is preceded by an acoustic tone—conditioned animals will blink when just the tone is heard The hippocampus is not required, but a circuit in the cerebellum is necessary for this reflex 1. Before training, a puff of air on the surface of the eye triggers a reflexive eye blink. 2. Information about the puff of air is also sent to the cerebellum. Although the cerebellum can send information to the cranial motor nuclei that trigger the eye blink, at this stage those synapses are inactive.
- Information converges on the cerebellum: The corneal stimulus (US) via the trigeminal pathway The auditory stimulus (CS) via the auditory nuclei 3. During conditioning, information about the sound of the bell also reaches the cerebellum. There, impulses from this auditory signal and the air puff converge on particular neurons. Repeated pairings of bell (CS) and air puff (US) strengthen particular synapses within the cerebellum.
- After conditioning, the tone has an enhanced effect on the cerebellar neurons 4. After training is complete, the sound of the bell now triggers activity in the cerebellum that drives the cranial motor nuclei to trigger an eye blink even if the air puff never happens. This is a conditioned response. The animal has learned that the ringing of the bell predicts that an air puff will soon hit the eye. 5. Repeated presentation of the bell without the air puff begins to weaken the cerebellar connections so that eventually the bell stops eliciting an eye blink. The animal has now learned that the bell no longer predicts an air puff.
- Donald Hebb proposed that when two neurons are repeatedly activated together, their synaptic connection will become stronger. These so-called Hebbian synapses could then act together to store memory traces. Hebb proposed this idea in the 1940s. It was confirmed by research conducted in the 1970s.
- Electrodes were placed within the rat hippocampus, positioned so that researchers could stimulate a group of presynaptic neurons and immediately record the electrical response of a group of postsynaptic neurons. Normal, low-level amounts of stimulation produced stable and predictable EPSPs. But, a high-frequency burst of electrical stimulation (called a tetanus) caused the presynaptic neurons to produce a high rate of action potentials, and subsequently, the postsynaptic cells produced MUCH larger EPSPs. The synapses appear to have become stronger and more effective. This long-lasting enhancement of synaptic transmission was called LTP (long-term potentiation).
- Long-term potentiation occurs at pathways in the hippocampal formation… formed by the hippocampus and the dentate gyrus (take a look at the cross-section of mouse hippocampus. Now let’s take a closer look at a single CA1 synapse onto the dentate gyrus, so we can take a closer look at the AMPA & NMDA receptors.
- CA1 = region of the hippocampus Normally the NMDA channel is blocked by an Mg2+ molecule. Only the AMPA channel functions in the exciting neuron. AMPA receptors are simple ligand-gated channels that allow Na to enter. Other acronyms on chart: CAMKII = calcium/calmodulin-dependent protein kinase II CREB = cAMP responsive element-binding protein Glu = glutamate PKC = protein kinase C TK = tyrosine kinase
- NMDA receptors are different. They are both ligand AND voltage-gated. They open in response to partial depolarization and GLU. When open, they allow CA2+ to enter the cell.
- Postsynaptic changes: With repeated activation of AMPA receptors, depolarization of the neuron drives Mg2+ ) out of the NMDA channel, allowing Ca2+ ) ions in. The rapid entry of Ca2+ ) ions trigger second messenger systems that lead to LTP, increasing the conductance of existing AMPA receptors and moving more into the membrane.
- Retrograde transmitters, perhaps nitric oxide, reach the presynaptic terminal to enhance NT release.
- These changes make the synapse more responsive. The postsynaptic cell now has a stronger response, as more NT is released and more AMPA receptors are present.
- These cells tend to fire synchronously. Because they fire together, they tend to drive the postsynaptic neuron to fire. These cells tend to fire at random, out of synchrony with one another. They rarely cause the postsynaptic neuron to fire.
- Is LTP a mechanism of memory formation? 1. Correlational observations: Covarying with memory, LTP can be induced within seconds, may last for days or weeks, and shows a vulnerable period that lasts for several minutes after induction. LTP resembles the vulnerability of STM to loss from accident or disease. 2. Somatic Intervention Experiments Drug treatments that interfere with LTP also impair learning. NMDA receptor blockade interferes with performance in the Morris water maze. Drugs that inhibit enzymes activated by NMDA receptors also interfere with memory formation. Knockout mice that lack functional NMDA receptors only in CA1 appear normal, but hippocampi are incapable of LTP and their memory is impaired. Transgenic mice that overexpress NMDA receptors have enhanced LTP and better than normal LTM. 3. Behavioral Intervention Experiments: Fear conditioning produces clear LTP in fear circuits in the amygdala (but nowhere else). Aversive learning in rats produces the same changes in electrophysiology and AMPA receptors as has been seen in LTP induced by electrodes. This seems to confirm what happened to H.M. His amnesia appears to have resulted from the loss of hippocampal tissue and mechanisms that would have allowed him to use LTP to consolidate STMs into LTMs.