17 Learning and Memory 17 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 17 Learning and Memory Neural Mechanisms of Memory • Memory Storage Requires Neuronal Remodeling • Invertebrate Nervous Systems Show Plasticity • Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits 17 Learning and Memory Neural Mechanisms of Memory (cont'd) • 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 17 Functional Perspectives on Memory Learning is the process of acquiring new information. Memory is: • The ability to store and retrieve information. • The specific information stored in the brain. 17 There Are Several Kinds of Memory and Learning Patient H.M. suffers from amnesia, or memory impairment. • Retrograde amnesia is the loss of memories formed before onset of amnesia. • Anterograde amnesia is the inability to form memories after onset of a disorder. 17 There Are Several Kinds of Memory and Learning Damage to the hippocampus can produce memory deficits. H.M.’s surgery removed the amygdala, the hippocampus, and some cortex. H.M.’s memory deficit was confined to verbal tasks. Figure 17.1 Brain Tissue Removed from Henry Molaison (Patient H.M.) Figure 17.2 Henry’s Performance on a Mirror-Tracing Task 17 There Are Several Kinds of Memory and Learning Two kinds of memory: • Declarative memory deals with what – facts and information acquired through learning that can be stated or described. • Nondeclarative (procedural) memory deals with how – shown by performance rather than recollection. Figure 17.3 Two Main Kinds of Memory: Declarative and Nondeclarative 17 There Are Several Kinds of Memory and Learning Damage to other areas can also cause memory loss. Patient N.A. has amnesia due to accidental damage to the dorsomedial thalamus. Like Henry Molaison, he has shortterm memory but cannot form declarative long-term memories. Figure 17.4 The Brain Damage in Patient N.A. 17 There Are Several Kinds of Memory and Learning Korsakoff’s syndrome is a memory deficiency caused by lack of thiamine – seen in chronic alcoholism. Brain damage occurs in mammillary bodies and basal frontal lobes. Patients often confabulate – fill in a gap in memory with a falsification. 17 There Are Several Kinds of Memory and Learning 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. 17 There Are Several Kinds of Memory and Learning 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. Figure 17.5 Subtypes of Declarative and Nondeclarative Memory 17 There Are Several Kinds of Memory and Learning Nonassociative learning involves a single stimulus presented once or repeated. Three types of nonassociative learning: • Habituation – a decreased response to repeated presentations of a stimulus. • Dishabituation – restoration of response amplitude after habituation. • Sensitization – prior strong stimulation increases response to most stimuli. 17 There Are Several Kinds of Memory and Learning Associative learning involves relations between events. • In classical conditioning – Pavlovian conditioning – a neutral stimulus is paired with another stimulus that elicits a response. Eventually the neutral stimulus by itself will elicit the response. 17 There Are Several Kinds of Memory and Learning • In instrumental conditioning – or operant conditioning – an association is made between: Behavior (the instrumental response). The consequences of the behavior (the reward). 17 Memory Has Temporal Stages: Short, Intermediate, and Long • Iconic memories are the briefest and store sensory impressions. • Short-term memories (STMs) usually last only for seconds, or throughout rehearsal. Short-term memory is also known as working memory. 17 Memory Has Temporal Stages: Short, Intermediate, and Long Working memory can be subdivided into three components, all supervised by a central executive: • Phonological loop – contains auditory information. • Visuospatial sketch pad – holds visual impressions. • Episodic buffer – contains more integrated information. 17 Memory Has Temporal Stages: Short, Intermediate, and Long • An intermediate-term memory (ITM) outlasts a STM, but is not permanent. • Long-term memories (LTMs) last for days to years. 17 Memory Has Temporal Stages: Short, Intermediate, and Long 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). Figure 17.6 Serial Position Curves from Immediate-Recall Experiments 17 Memory Has Temporal Stages: Short, Intermediate, and Long Long-term memory has a large capacity, but can be altered. The memory trace, or record of a learning experience, can be affected by other events before or after. Each time a memory trace is activated and recalled, it is subject to changes. 17 Successive Processes Capture, Store, and Retrieve Information in the Brain A functional memory system incorporates three aspects: • Encoding – sensory information is encoded into short-term memory. • Consolidation – information may be consolidated into long-term storage. • Retrieval – stored information is retrieved. Figure 17.7 Hypothesized Memory Processes: Encoding, Consolidation, and Retrieval 17 Successive Processes Capture, Store, and Retrieve Information in the Brain 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. 17 Successive Processes Capture, Store, and Retrieve Information in the Brain 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. Figure 17.8 Encoding, Consolidation, and Retrieval of Declarative Memories 17 Successive Processes Capture, Store, and Retrieve Information in the Brain The process of retrieving information from LTM can cause memories to become unstable and susceptible to to disruption or alteration. Reconsolidation is the return of a memory trace to stable long-term storage, after recall. 17 Successive Processes Capture, Store, and Retrieve Information in the Brain Strong emotions can enhance memory formation and retrieval. Many compounds participate: acetylcholine, epinephrine, norepinephrine, vasopressin, the opioids, and GABA. Drugs that are agonists or antagonists of these can be involved. 17 Successive Processes Capture, Store, and Retrieve Information in the Brain In posttraumatic stress disorder (PTSD), memories produce a stress hormone response that further reinforces the memory. Treatments that can block chemicals acting on the basolateral amygdala may alter the effect of emotion on memories. Box 17.2 The Amygdala and Memory 17 Different Brain Regions Process Different Aspects of Memory Testing declarative memories in monkeys: • Delayed non-matching-to-sample task – must choose the object that was not seen previously. Medial temporal lobe damage causes impairment on this task. Figure 17.9 The Delayed Non-Matching-to-Sample Task Figure 17.10 Memory Performance after Medial Temporal Lobe Lesions 17 Different Brain Regions Process Different Aspects of Memory 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. 17 Different Brain Regions Process Different Aspects of Memory Episodic and semantic memories are processed in different areas. Episodic (autobiographical) memories cause greater activation of the right frontal and temporal lobes. Figure 17.11 My Story versus Your Story 17 Different Brain Regions Process Different Aspects of Memory Early research indicated that animals form a cognitive map – a mental representation of a spatial relationship. Latent learning has taken place but has not been demonstrated in performance tasks. Figure 17.12 Biological Psychologists at Work 17 Different Brain Regions Process Different Aspects of Memory The hippocampus is also important in spatial learning. It contains place cells that become active when in, or moving toward, a particular location. Grid cells and border cells are neurons that fire when animal is at an intersection or perimeter of an abstract grid map. 17 Different Brain Regions Process Different Aspects of Memory 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. 17 Different Brain Regions Process Different Aspects of Memory Comparisons of behaviors and brain anatomy show that increased demand for spatial memory results in increased hippocampal size in mammals and birds. In food-storing species of birds, the hippocampus is larger but only if used to retrieve stored food. 17 Different Brain Regions Process Different Aspects of Memory Spatial memory and hippocampal size can change within the life span. In some species, there can be be sex differences in spatial memory, depending on behavior. Polygynous male meadow voles travel further and have a larger hippocampus than females or monogamous pine vole males. Figure 17.13 Sex, Memory, and Hippocampal Size 17 Different Brain Regions Process Different Aspects of Memory Imaging studies help to understand learning and memory for different skills: • Sensorimotor skills, such as mirror-tracing. • Perceptual skills – learning to read mirrorreversed text. • Cognitive skills – planning and problem solving. 17 Different Brain Regions Process Different Aspects of Memory 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. 17 Different Brain Regions Process Different Aspects of Memory During conceptual priming, there is reduced activity compared to baseline in only the left frontal cortex. Conceptual priming reflects the meaning of the stimulus. 17 Different Brain Regions Process Different Aspects of Memory 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. 17 Different Brain Regions Process Different Aspects of Memory 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. 17 Different Brain Regions Process Different Aspects of Memory 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. Figure 17.14 Tests of Specific Attributes of Memory (Part 1) 17 Different Brain Regions Process Different Aspects of Memory 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. Figure 17.14 Tests of Specific Attributes of Memory (Part 2) 17 Different Brain Regions Process Different Aspects of Memory 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. Figure 17.14 Tests of Specific Attributes of Memory (Part 3) 17 Different Brain Regions Process Different Aspects of Memory 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. Figure 17.15 Brain Regions Involved in Different Kinds of Learning and Memory 17 Neural Mechanisms of Memory 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 environment. 17 Memory Storage Requires Neuronal Remodeling Sherrington speculated that alterations in synapses were the basis for learning. Hebb proposed that when two neurons are repeatedly activated together, their synaptic connection will become stronger. Cell assemblies - ensembles of neurons linked via Hebbian synapses could store memory traces. 17 Memory Storage Requires Neuronal Remodeling Physiological changes at synapses may store information. Changes can be presynaptic, or postsynaptic, or both. Changes can include increased neurotransmitter release, or effectiveness of receptors. 17 Memory Storage Requires Neuronal Remodeling 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 receptors. Figure 17.16 Synaptic Changes That May Store Memories (Part 1) 17 Memory Storage Requires Neuronal Remodeling Changes in the rate of inactivation of transmitter would also increase effects. Inputs from other neurons might increase or decrease neurotransmitter release. 17 Memory Storage Requires Neuronal Remodeling 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. Figure 17.16 Synaptic Changes That May Store Memories (Part 2) 17 Memory Storage Requires Neuronal Remodeling Lab animals living in a complex environment demonstrated biochemical and anatomical brain changes. Three housing conditions: • Standard condition (SC) • Impoverished (or isolated) condition (IC) • Enriched condition (EC) Figure 17.17 Experimental Environments to Test the Effects of Enrichment on Learning and Brain Measures 17 Memory Storage Requires Neuronal Remodeling Animals housed in EC developed: • Heavier, thicker cortex. • Enhanced cholinergic activity. • Larger cortical synapses. • Altered gene expression. • Enhanced recovery from brain damage. 17 Memory Storage Requires Neuronal Remodeling EC also increases growth in dendrites: • More dendritic spines suggesting more synapses. • Increased dendritic branching, especially on basal dendrites, nearer the cell body. Figure 17.18 Measurement of Dendritic Branching (Part 1) Figure 17.18 Measurement of Dendritic Branching (Part 2) 17 Invertebrate Nervous Systems Show Plasticity Aplysia is used to study plastic synaptic changes in neural circuits. The advantages of Aplysia: • Has fewer nerve cells. • Can create detailed circuit maps for particular behaviors – little variation between individuals. 17 Invertebrate Nervous Systems Show Plasticity Habituation is studied in Aplysia. Squirts of water on its siphon causes it to retract its gill. After repeated squirts, the animal retracts the gills less – it has learned that the water poses no danger. Figure 17.19 The Sea Slug Aplysia 17 Invertebrate Nervous Systems Show Plasticity The habituation is caused by synaptic changes between the sensory cell in the siphon and the motoneuron that retracts the gill. Less transmitter released in the synapse results in less retraction. Figure 17.20 Synaptic Plasticity Underlying Habituation in Aplysia (Part 1) 17 Invertebrate Nervous Systems Show Plasticity Over several days the animal habituates faster, representing longterm habituation. The number of synapses between the sensory cell and the motoneuron is reduced. Figure 17.20 Synaptic Plasticity Underlying Habituation in Aplysia (Part 2) 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits Long-term potentiation (LTP) – a stable and enduring increase in the effectiveness of synapses. Tetanus – a brief increase of electrical stimulation that triggers thousands of axon potentials. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits Synapses in LTP behave like Hebbian synapses: • Tetanus drives repeated firing. • Postsynaptic targets fire repeatedly due to the stimulation. • Synapses are stronger than before. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits LTP occurs at several sites in the hippocampal formation – formed by the hippocampus, the dentate gyrus and the subiculum. Regions CA1 and CA3 are most often studied. Figure 17.21 Long-Term Potentiation Occurs in the Hippocampus (Part 1) Figure 17.21 Long-Term Potentiation Occurs in the Hippocampus (Part 2) Figure 17.21 Long-Term Potentiation Occurs in the Hippocampus (Part 3) 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits The CA1 region has both NMDA and AMPA receptors. Glutamate first activates AMPA receptors. NMDA receptors do not respond until enough AMPA receptors are stimulated and the neuron is partially depolarized. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits NMDA receptors at rest have a magnesium ion (Mg2+) block on their calcium (Ca2+) channels. After partial depolarization, the block is removed and the NMDA receptor allows Ca2+ to enter in response to glutamate. Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 1) Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 2) Figure 17.22 Roles of NMDA and AMPA Receptors in the Induction of LTP in CA1 Region (Part 3) 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits The large Ca2+ influx activates certain protein kinases – enzymes that add phosphate groups to protein molecules. One protein kinase is CaMKII – it affects AMPA receptors in several ways: • Causes more AMPA receptors to be produced and inserted in the postsynaptic membrane. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits CaMKII : • Moves existing nearby AMPA receptors into the active synapse. • Increases conductance of Na+ and K+ ions in membrane-bound receptors. These effects all increase the synaptic sensitivity to glutamate. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits The activated protein kinases also trigger protein synthesis. Kinases activate CREB – cAMP responsive element-binding protein. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits 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. Figure 17.23 Steps in the Neurochemical Cascade during the Induction of LTP 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits Strong stimulation of a postsynaptic cell releases a retrograde messenger that travels across the synapse and alters function in the presynaptic neuron. More glutamate is released and the synapse is strengthened. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits There is evidence that LTP may be one part of learning and memory formation: • Correlational observations – time course of LTP is similar to that of memory formation. 17 Synaptic Plasticity Can Be Measured in Simple Hippocampal Circuits • Somatic intervention experiments – pharmacological treatments that block LTP impair learning. • Behavioral intervention experiments – show that training an animal in a memory task can induce LTP. 17 Some Simple Learning Relies on Circuits in the Mammalian Cerebellum Researchers use the eye-blink reflex to study neural circuits in mammals. An air puff is preceded by an acoustic tone – conditioned animals will blink when just the tone is heard. A circuit in the cerebellum is necessary for this reflex. Figure 17.24 Functioning of the Neural Circuit for Conditioning of the Eye-Blink Reflex (Part 1) Figure 17.24 Functioning of the Neural Circuit for Conditioning of the Eye-Blink Reflex (Part 2) Figure 17.24 Functioning of the Neural Circuit for Conditioning of the Eye-Blink Reflex (Part 3) 17 Some Simple Learning Relies on Circuits in the Mammalian Cerebellum Neurons converge in the interpositus nucleus of the cerebellum. Blocking GABA in this area stops the behavioral response. The cerebellum is also important in conditioning of emotions and cognitive learning, as shown by humans with cerebellar damage. 17 In the Adult Brain, Newly Born Neurons May Aid Learning Neurogenesis, or birth of new neurons, occurs mainly in the dentate gyrus in adult mammals. Neurogenesis and neuronal survival can be enhanced by exercise, environmental enrichment, and memory tasks. Reproductive hormones and experience are also an influence. 17 In the Adult Brain, Newly Born Neurons May Aid Learning In some studies, neurogenesis has been implicated in hippocampusdependent learning. Conditional knockout mice, with neurogenesis turned off in adults, showed impaired spatial learning but were otherwise normal. Figure 17.25 Neurogenesis in the Dentate Gyrus 17 Learning and Memory Change as We Age Some causes of memory problems in old age: • Impairments of coding and retrieval – less cortical activation in some tasks. • Loss of neurons and/or neural connections – some parts of the brain lose a larger proportion of volume. Figure 17.26 Active Brain Regions during Encoding and Retrieval Tasks in Young and Old People 17 Learning and Memory Change as We Age • Deterioration of cholinergic pathways - the septal complex and the nucleus basalis of Meynert (NBM) provide cholinergic input to the hippocampus. These pathways seem to be involved in Alzheimer’s disease. • Impaired coding by place cells – neurons encode less spatial information. 17 Learning and Memory Change as We Age Nootropics are a class of drugs that enhance cognitive function. Cholinesterase inhibitors result can have a positive effect on memory and cognition. Ampakines work to improve LTP in the hippocampus. 17 Learning and Memory Change as We Age Lifestyle factors can help reduce cognitive decline: • Living in a favorable environment. • Involvement in enriching activities. • Having a partner of high cognitive status.