PSYC326_Chapter 13

Amnesia: stimulus-response learning

H. M. and another patient with anterograde amnesia could acquire a classically conditioned eyeblink response. H. M. showed retention of the task two years later: He acquired the response again in one-tenth the number of trials that were needed previously. Successfully trained patient H. M. on an operant conditioning task

Types of memory: long-term memory - declarative memories - semantic memories

"What" Facts Do not include information about the context in which the facts were learned Less specific than episodic memories Semantic memories can be acquired gradually, over time

Types of learning: stimulus-response learning

Ability to learn to perform a particular behavior when a particular stimulus is present - establishment of connections between circuits involved in perception and those involved in movement Automatic responses - defensive reflex; or a complicated sequence of movements - performing a piece of music Includes: classical conditioning and operant conditioning. Conditioning: learning that may require several exposures to stimuli to produce a lasting change in behavior

Stimulus-response learning: reinforcement - function of the reinforcement system

Reinforcement system performs two functions 1) Detect the presence of a reinforcing stimulus (recognize that something good has just happened) 2) Strengthen the connections between the neurons that detect the discriminative stimulus and the neurons that produce the operant response

Types of learning: stimulus-response learning - reinforcement

Reinforcement causes changes in an animal's nervous system that increase the likelihood that a specific stimulus will elicit a particular response behavior Process of reinforcement strengthens a connection between neural circuits involved in perception and those involved in movement - Brain contains reinforcement mechanisms that control this process Positive reinforcement contingency: if you do a behaviour that is followed by something you like - you are more likely to do that behaviour again

Long-term potentiation: induction of long-term potentiation - electrical stimulation to the perforant path

1) A single pulse of electrical stimulation is delivered to the perforant path 2) Resulting population EPSP is recorded in the dentate gyrus - The population EPSP: extracellular measurement of the EPSPs produced by the synapses of the perforant path axons with the dentate granule cells - Size of the first population EPSP indicates the strength of the synaptic connections before long-term potentiation has taken place 3) Evidence that long-term potentiation has occurred: periodically delivering single pulses to the perforant path and recording the response in the dentate gyrus - If the response is greater than it was before the burst of pulses was delivered, long-term potentiation has occurred A series of pulses delivered at a high rate all in one burst will produce LTP - Same number of pulses given at a slow rate will not A rapid rate of stimulation causes the EPSPs to summate, because each successive EPSP occurs before the previous one has dissipated - rapid stimulation depolarizes the postsynaptic membrane much more than slow stimulation does

Types of learning: stimulus-response learning - differences between classical and operant conditioning

1) Classical conditioning: automatic reflexes that do not have to be learned. Operant conditioning: brand new behaviors that have been learned. 2) Classical conditioning: an association between two stimuli. Operant conditioning: association between a stimulus and a response 3) Operant conditioning: permits an organism to change its behavior according to the consequences of that behavior

Long-term potentiation: role of AMPA receptors - location

1) Establishment of LTP first caused movement of AMPA receptors into the postsynaptic membranes of dendritic spines from adjacent nonsynaptic regions of the dendrites 2) AMPA receptors were carried from the interior of the cell to the dendritic shaft, where they replaced the AMPA receptors that had been inserted in the postsynaptic membrane of the spines

Amnesia: role of the hippocampus

1. The hippocampus is not the location of long-term memories nor is it necessary for the retrieval of long-term memories 2. The hippocampus is not the location of short-term memories 3. The hippocampus is involved in converting short-term memories into long-term memories

Types of memory: sensory memory

A brief period of time that the initial sensation of environmental stimuli is initially remembered Occurs in each of the senses and allows an individual to retain the experience of the sensation slightly longer than the original stimulus. Experienced as a brief period in which sensory experiences can be remembered as repeating or "echoing"

Types of learning: motor learning

A component of stimulus- response learning Habitual learning - don't have to think moment to moment Spinal cord and cortical motor structures Establishment of changes (responses) within motor systems following a stimulus Cannot occur without sensory stimulus from the environment Differs from other forms of learning primarily in the degree to which new forms of behavior are learned - The more novel the behavior, the more the neural circuits in the motor systems of the brain must be modified - Complex, original behaviour Changes in responses of motor system following a stimulus

Relational learning: role of the hippocampus - consolidation of memories - episodic and semantic memories - semantic dementia

A degenerative neurological disorder - temporal cortex plays an important role in storing semantic information. - Caused by degeneration of the neocortex of the anterolateral temporal lobe Early stages of the degenerative process: hippocampal formation and the rest of the medial temporal lobe are not affected

Types of learning: perceptual learning

Ability to learn to recognize stimuli that have been perceived before Sensory and association cortex Primary function: identify and categorize objects and situations - Unless we have learned to recognize something, we cannot learn how we should behave with respect to it Each of our sensory systems is capable of perceptual learning Perceptual learning is accomplished primarily by changes in the sensory association cortex - learning to recognize complex visual stimuli involves changes in the visual association cortex, learning to recognize complex auditory stimuli involves changes in the auditory association cortex etc.

Relational learning: role of the hippocampus - consolidation of memories - episodic and semantic memories

Acquisition of episodic and semantic memories requires the participation of the hippocampus Damage limited to the hippocampal formation: anterograde amnesia for semantic and episodic information Sensory association cortex: perceptual memories and episodic memories are located here Semantic memories are not simply perceptual memories

Stimulus-response learning: reinforcement - role of ventral tegmental area (VTA)

Activated by natural reinforcers (food, water), direct stimulation (electrical, chemical (DA, L-DOPA), drugs of abuse - Unnatural reinforcers overwhelm the natural reinforcers because of how powerful they are - addicts do not find normal things as rewarding Detects new reinforcing stimuli VTA recognises there is something new to learn - If there is nothing new learn - they are not activated - If we get the same reward over and over again - the VTA become less activated. There has to be a change in new rewards Block of dopamine: you do not find natural activities very rewarding Very powerful motivation and reward - Activating this system will making activities more rewarding and learning will increase Projections: prefrontal cortex - Prefrontal cortex: involved in short term memories, making decisions, evaluating what is going on Very sensitive to what it can possible learn in particular circumstances VTA is not where learning is occurring but it is helping solidify memories in the areas where learning is occurring

Stimulus-response learning: reinforcement - neural circuits involved in reinforcement

Activity of dopaminergic neurons: important role in reinforcement. - Dopaminergic neurons begins in the ventral tegmental area (VTA) of the midbrain and projects to amygdala, hippocampus, and nucleus accumbens (NAC) Projection from NAC: ventral part of the basal ganglia (involved in learning) Mesocortical system: plays a role in reinforcement - Begins: ventral tegmental area - Projects: prefrontal cortex, the limbic cortex, and the hippocampus

Amnesia: relational learning

Although the patients can learn to perform these tasks, they do not remember anything about having learned them

Amnesia: role of the hippocampus - retrograde amnesia: retrieval

Anterograde amnesia is usually accompanied by retrograde amnesia Differential role of the hippocampal formation in recent memories and older ones - Retrieval of the youngest memories caused the greatest activation of the hippocampus - Retrieval of the oldest memories caused the least activation - The opposite effect was seen in the frontal cortex Memories initially stored in the hippocampus are gradually transferred to the frontal cortex Amnesia did not represent a total failure in learning ability - When patients are appropriately trained and tested, we find that they are capable of three of the four major types of learning: 1) perceptual, 2) stimulus-response, and 3) motor learning Brain damage, electrical stimulation is usually done by electroconvulsive shock

Amnesia: temporal lobes and H.M.

Anterograde amnesia: caused by damage to the temporal lobes, where the hippocampus is located Bilateral removal of the medial temporal lobe produced a memory impairment that was identical to Korsakoff's syndrome H. M: received surgery in an attempt to treat his severe epilepsy, which could not be controlled even by high doses of anticonvulsant medication - The surgery successfully treated H. M.'s seizure disorder. Operation had produced a serious memory impairment - Critical site of damage: hippocampus.

Amnesia: anterograde and retrograde

Anterograde amnesia: difficulty in learning new information - Basic abilities of perceptual learning, stimulus-response learning, and motor learning are intact - Complex relational learning is gone - Usually, there is also a retrograde amnesia for events that occurred for a period of time before the brain damage occurred. Pure anterograde amnesia: can remember events that occurred in the past but cannot retain information encountered after the damage - rare. Retrograde amnesia: inability to remember events that happened before the brain damage occurred Anterograde amnesia is relatively more common than retrograde amnesia.

Stimulus-response learning: operant conditioning - basal ganglia - pathways

As learned behaviors become automatic and routine, they are "transferred" to the basal ganglia 1) As we deliberately perform a complex behavior, the basal ganglia receive information about the stimuli that are present and the responses we are making 2) At first the basal ganglia are passive "observers" of the situation. As the behaviors are repeated again and again - the basal ganglia begin to learn what to do 3) Eventually, they take over most of the details of the process, leaving the transcortical circuits free to do something else

Motor learning: role of the basal ganglia

Basal ganglia: role in stimulus-response and motor learning - Non-declarative motor memories (habits, skills) People with diseases of the basal ganglia have deficits that can be attributed to difficulty in learning automatic responses - Parkinson's disease: impaired on learning a visually cued operant conditioning task - Huntington's disease: failed to learn a sequence of button presses.

Amnesia: role of the hippocampus - anterograde amnesia: consolidation - CA1

CA1 is especially rich in NMDA receptors - Long-term potentiation can quickly become established there Drugs that block NMDA receptors: period of anoxia is much less likely to produce brain damage

Stimulus-response learning: operant conditioning - basal ganglia - pathways - overview

Caudate nucleus and the putamen receive sensory information from all regions of the cerebral cortex. - Frontal lobes: movements that are planned or in progress Outputs of the caudate nucleus and the putamen: globus pallidus Outputs of the globus pallidus: 1) Frontal cortex (premotor and supplementary motor cortex): plans for movements are made 2) Primary motor cortex: plans are executed 1) Caudate nucleus and putamen receives information 2) Globus pallidus 3) Frontal cortex - premotor and supplementary motor cortex 4) Primary motor cortex

Stimulus-response learning: operant conditioning - basal ganglia

Circuits responsible for operant conditioning: 1) Begin in various regions of the sensory association cortex where perception takes place 2) End in the motor association cortex of the frontal lobe (controls movements) Major pathways between the sensory association cortex and the motor association cortex: 1) Direct transcortical connections (connections from one area of the cerebral cortex to another) 2) Connections via the basal ganglia and thalamus

Stimulus-response learning: classical conditioning - amygdala - lateral nucleus

Conditioned emotional response (CER): lateral nucleus - weak at first but when the pairing is stronger, it has a greater activation Information about the CS comes here after being processed by the auditory cortex - Receives information about the US from the somatosensory system - These two sources of information converge in the lateral nucleus - synaptic changes responsible for learning could take place in this location Contains neurons whose axons project to the central nucleus. - Terminal buttons from neurons that transmit auditory and somatosensory information to the lateral nucleus form synapses with dendritic spines on these neurons Neurons in this nucleus fire --> activates neurons in the central nucleus --> evoking an unlearned emotional response Tone is paired with the painful stimulus: weak synapses in the lateral amygdala are strengthened - The synaptic changes responsible for this type of learning take place within this circuit

Amnesia: role of the hippocampus - anterograde amnesia: consolidation - R.B.

Damage restricted to the hippocampal formation produces anterograde amnesia, including deficits in consolidation R.B.: 52-year-old man with a history of heart trouble, sustained a cardiac arrest. Heart was successfully restarted, the period of anoxia caused by the temporary halt in blood flow resulted in brain damage - Primary symptom of brain damage: permanent anterograde amnesia CA1: region of the hippocampal formation - primarily affected and the neurons had completely degenerated

Types of memory: long-term memory - declarative memories

Declarative memory/explicit memory Events and facts that we can think and talk about Episodic and semantic memories

Long-term potentiation: role of AMPA receptors

Dendritic spines on CA1 pyramidal cells contain two types of glutamate receptors: 1) NMDA receptors 2) AMPA receptors Strengthening of an individual synapse is accomplished by insertion of additional AMPA receptors into the postsynaptic membrane of the dendritic spine AMPA receptors control sodium channels - when they are activated by glutamate, they produce EPSPs in the membrane of the dendritic spine. More AMPA receptors present --> release of glutamate by the presynaptic terminal button causes a larger excitatory postsynaptic potential. - Synapse becomes stronger

Amnesia: relational learning - spatial memory - place cells and spatial receptive fields

Different neurons had different spatial receptive fields - they responded when the animals were in different locations A particular neuron might fire 20x per second when the animal was in a particular location but only a few times per hour when the animal was located elsewhere. The fact that neurons in the hippocampal formation have spatial receptive fields does not mean that each neuron encodes a particular location The animal has to be oriented in a particular way - he has to be pointed in a particular orientation for the cells to be active The cells are pretty stable - that same cell will be activated for that particular location Place cells in older individuals - the place cells are not as stable - A place cell that showed activity in one location one day may not show activation in the same area the next day - Memory is not as stable in younger individuals The same cell can react in different ways - An animal may start at the same place and learns that he needs to make an alternating sequence - right or left. When animals are going down the central area their hippocampus indicates anticipated direction - Hippocampus is anticipating the current experience with past experiences

Long-term potentiation: induction of long-term potentiation

Electrical stimulation of circuits within the hippocampal formation can lead to long-term synaptic changes that seem to be among those responsible for learning Intense electrical stimulation of axons leading from the entorhinal cortex to the dentate gyrus increased the magnitude of excitatory postsynaptic potentials in the postsynaptic neurons - This increase has come to be called long-term potentiation (LTP) - Increase in EPSPs is relatively long-term, lasting for months at a time The primary input to the hippocampal formation: entorhinal cortex - Axons of neurons pass through the perforant path and form synapses with the granule cells of the dentate gyrus

Relational learning: role of the hippocampus - reconsolidation of memories - electroconvulsive therapy

Electroconvulsive therapy: side effect - period of retrograde amnesia - Used to treat cases of severe depression - Application of electricity through electrodes placed on a person's scalp - excites so many neurons in the brain that it produces a seizure - Seizure erases short-term memories present at the time and thus prevents consolidation of these memories. Long-term memories (not affected by seizures) were vulnerable to disruption by electroconvulsive shock (ECS) if a reminder of the original learning experience was first presented - ECS given right after a learning experience prevented consolidation - disrupted the brain activity initiated by the training session and consequently interfered with consolidation. - ECS given a day later did not prevent consolidation - memory had already been consolidated Reactivation of the memory makes it susceptible to disruption.

Long-term potentiation: role of AMPA receptors - CaM-KII

Entry of calcium ions into the dendritic spine causes AMPA receptors to move into the postsynaptic membrane 1) Activation of several enzymes - CaM-KII: an enzyme found in dendritic spines 2) After LTP was established in hippocampal neurons - CaM- KII molecules accumulated in the postsynaptic densities of dendritic spines Injection of activated CaM-KII directly into CA1 strengthened synaptic transmission in those cells - Moves more AMPA receptors into postsynaptic membrane making it a stronger AMPA synapse CaM-KII is a calcium-dependent enzyme - inactive until a calcium ion binds with it and activates it

Long-term potentiation: role of NMDA receptors - calcium ions

Entry of calcium ions through the ion channels controlled by NMDA receptors is an essential step in long-term potentiation AP5: a drug that blocks NMDA receptors - prevents calcium ions from entering the dendritic spines and blocks the establishment of LTP - Activation of NMDA receptors is necessary for the first step in the process of events that establishes LTP: the entry of calcium ions into dendritic spines.

Long-term potentiation: role of synaptic changes - postsynaptic changes

Establishment of LTP includes changes in the size and shape of dendritic spines LTP causes the enlargement of thin spines into fatter, mushroom-shaped spines Establishment of LTP causes the growth of new dendritic spines After 15-19 hours: new spines formed synaptic connections with terminals of nearby axons

Types of memory: long-term memory - declarative memories - episodic memories

Events, when, where Involve context Include information about when and under what conditions a particular episode occurred Order in which the events in the episode took place Specific to a particular time and place because a given episode occurs only once Episodic memories must be learned all at once

Types of learning

Four basic forms: 1) Stimulus- response learning 2) Motor learning 3) Perceptual learning 4) Relational learning A particular learning situation can involve varying amounts of all three types of learning: perceptual, stimulus-response, and motor

Amnesia: relational learning - declarative and nondeclarative memories

H. M. learned to make the correct response (press a panel with a picture of a circle on it), he was unable to recall having done so - Once H. M. had learned the task, the experimenters interrupted him, distract him, and then asked him to say what he was supposed to do - he had absolutely no idea. - When they turned on the stimuli again - H.M. immediately made the correct response Patient E. P.: developed anterograde amnesia - destroyed lots of his medial temporal lobe - Taught E. P. to point to a particular member of each of a series of eight pairs of objects. He eventually learned to do so, but he had no declarative memory of which objects were correct - E. P. learned a nondeclarative stimulus-response task without at the same time acquiring any declarative memories about what he had learned

Amnesia: role of the hippocampus - anterograde amnesia: consolidation - hippocampal formation and consolidation of relational memories

Hippocampal formation: consolidation of relational memories and transfering into the cerebral cortex - Consolidation—converting short-term memories to long- term memories. Morris water maze and tested mice's memory of the location of the platform - Hippocampus was deactivated one day after training - mice showed no memory of the task - Hippocampus was deactivated 30 days after training - performance was normal - Inactivation of several regions of the cerebral cortex impaired memory retrieval 30 days after training but not one day after training Hippocampus is required for newly learned spatial information but not for information learned 30 days previously

Relational learning: role of the hippocampus

Hippocampal formation: dentate gyrus, regions called the CA fields of the hippocampus, and the subiculum (and its subregions) - Important input: entorhinal cortex (neurons there have axons that terminate in the dentate gyrus, CA3, and CA1) Entorhinal cortex - Inputs: amygdala, various regions of the limbic cortex, all association regions of the neocortex Outputs of the hippocampal system: primarily from field CA1 and the subiculum Korsakoff's syndrome (cause of the anterograde amnesia) or difficulty learning new information - Degeneration of the mammillary bodies

Amnesia: relational learning - spatial memory - lesion to the hippocampus - birds and rodents

Hippocampal lesions disrupt the ability to keep track of and remember spatial locations Hippocampal lesions disrupted navigation in homing pigeons Hippocampal formation of species of birds and rodents that normally store seeds in hidden caches and later retrieve them is larger than that of animals without this ability - Individual caching birds that needed to store more seeds to survive the winter in harsher environments had correspondingly larger hippocampal regions.

Amnesia: relational learning - spatial memory

Hippocampal lesions produces deficits in spatial memory H. M. was unable to find his way around his environment after moving from his preamnesia home - Spatial information: anterograde amnesia - unable to consolidate information about the location of rooms, corridors, buildings, roads, and other important items in their environment Bilateral medial temporal lobe lesions produce the most profound impairment in spatial memory - Significant deficits can be produced by damage that is limited to the right hemisphere - Lesion of the right parahippocampal gyrus: lost his ability to find his way around a new environment

Long-term potentiation: Hebb rule

If a synapse repeatedly becomes active at about the same time that the postsynaptic neurons fires, changes will take place in the structure or chemistry of the synapse that will strengthen the synapse and make the production of EPSPs more likely - "Neurons that fire together, wire together" The act of firing strengthens any synapse with the motor neuron that has just been active - after several pairings of the two stimuli and after several increments of strengthening, synapses becomes strong enough to cause the motor neuron to fire by itself - Learning has occurred Learning must involve synaptic plasticity: changes in the structure or biochemistry of synapses that alter their effects on postsynaptic neurons

Long-term potentiation: role of NMDA receptors - dendritic spikes

If dendritic spikes are blocked by the administration of a toxin (tetrodotoxin), LTP does not occur

Relational learning: role of the hippocampus - reconsolidation of memories

If we learn something new about a particular subject, our memories pertaining to that subject must somehow be modified If you learn more about something you will acquire a larger and larger number of interconnected memories When you have made a long-term memory you can retrieve that information and make use of that

Long-term potentiation: role of NMDA receptors - polarization and calcium

If weak synapses are active by themselves, nothing happens because the membrane of the dendritic spine does not depolarize sufficiently for the calcium channels controlled by the NMDA receptors to open. If activity of strong synapses located elsewhere on the postsynaptic cell has caused the cell to fire - dendritic spike will depolarize the postsynaptic membrane enough to eject the magnesium ions from the calcium channels of the NMDA receptors in the dendritic spines - If some weak synapses become active then - calcium will enter the dendritic spines and cause the synapses to become strengthened - special properties of NMDA receptors allow LTP to occur

Stimulus-response learning: classical conditioning - amygdala

Important in classically conditioned emotional responses An aversive stimulus: produces a variety of behavioral, autonomic, and hormonal responses

Types of learning: stimulus-response learning - operant conditioning

Instrumental conditioning Reinforcing or punishing outcome follows a specific behavior in a specific situation Law of effect: - Reinforcer: increases the likelihood of the behavior occurring again in the future - synapse does get stronger - Punisher: decreases the likelihood of the behavior occurring again in the future - synapse does not get stronger Three elements 1) A discriminative stimulus 2) A response 3) A reinforcing stimulus

Long-term potentiation: role of synaptic changes - protein synthesis - early LTP

LTP consists of stages Early LTP (E-LTP): 1. Presynaptic membrane depolarization 2. Presynaptic release of glutamate 3. Postsynaptic activation of ligand- and voltage-gated NMDA receptors 4. Entry of calcium ions into the postsynaptic cell, and subsequent activation of enzymes such as CaM-KII 5. Movement of AMPA receptors into the postsynaptic membrane 6. Postsynaptic NO-synthase increases release of NO, which retrogradely travels to presynaptic terminal to increases release of glutamate

Overview of learning and memory

Learning allows us to acquire new information. It is the process by which experiences change our nervous system and our behavior. Memories: long-term changes in the nervous system following learning - Persist over time and are formed when something is learned. Learning and creating a memory physically changes the structure of the nervous system - neural circuits that participate in perceiving, performing, thinking, planning, and behaving. Learning, memory, and their effects on behavior are only possible through plasticity - Nervous system demonstrates synaptic plasticity among existing neurons in learning and forming memories

Types of learning: relational learning

Learning the relationships among individual stimuli - Connection between brain areas - accomplished as a result of learning Sensory relationships More complex - different stimulus features to the environment - Depending on the context - we will act differently Hippocampus, cortex Perception of spatial location—spatial learning A special system that involves the hippocampus and associated structures: perform coordinating functions required for many types of learning that go beyond simple perceptual, stimulus-response, or motor learning

Retaining perceptual information in short-term memory

Learning to recognize a stimulus involves synaptic changes in the appropriate regions of the sensory association cortex that establish new circuits of neurons - Recognition of a stimulus: sensory input activates established sets of neural circuits Short-term memory of a stimulus: activity of these circuits (or other circuits that are activated by them) continues even after the stimulus disappears

Stimulus-response learning: operant conditioning - basal ganglia - pathways - caudate nucleus

Lesions of the basal ganglia: disrupt operant conditioning but do not affect other forms of learning Activity of caudate neurons: correlated with the animals' rate of learning - Further activation during the reinforcement: learn stimulus-response association more quickly

Stimulus-response learning: reinforcement - role of dopamine in reinforcement - process and LTP

Let's consider a hungry rat learning to press a lever and obtain food. 1) One element activates only weak synapses on motor neurons responsible for a movement that causes a lever press 2) Second element (particular circumstance that happened to induce the animal to press the lever) activates strong synapses, making the neurons fire 3) The third element - only if the response is followed by a reinforcing stimulus --> reinforcement mechanism triggers the secretion of a neurotransmitter or neuromodulator throughout the region in which the synaptic changes take place 4) Chemical is the third element - it can strength weak synapses - Dopamine serves such a role LTP: essential for operant conditioning and that dopamine is an essential ingredient in long-lasting long-term potentiation.

Long-term potentiation: role of synaptic changes - protein synthesis - long-lasting LTP

Long-lasting LTP (L-LTP): lasts more than a few hours requires protein synthesis Drugs that block protein synthesis prevented the establishment of L-LTP in field CA1 - Drug was administered before, during, or immediately after a prolonged burst of stimulation was delivered - E-LTP occurred, but it disappeared a few hours later - If the drug was administered one hour after the synapses had been stimulated - LTP persisted Protein synthesis is not necessary for the establishment of E-LTP, but it is required for establishing the later phase of L-LTP - normally occurs within an hour of the establishment of E-LTP

Long-term potentiation: role of synaptic changes - protein synthesis - long-term depression

Long-term depression (LTD): can be induced by low-frequency stimulation and results in decreased synaptic strength and fewer AMPA receptors in the postsynaptic membrane Neural circuits involved in creating memories are established by strengthening some synapses through LTP and weakening others through LTD.

Stimulus-response learning: classical conditioning - glutamate - long-term potentiation

Long-term potentiation (LTP): a series of synaptic changes involved in changes in the lateral amygdala responsible for acquisition of a conditioned emotional response LTP is accomplished through the activation of NMDA receptors and the insertion of additional AMPA receptors into the postsynaptic membrane - These synaptic changes in the glutamate system serve to increase the EPSP to the postsynaptic cell Learning experiences cause additional AMPA receptors to be inserted and increased EPSPs to dendritic spines of synapses between lateral amygdala neurons and axons of the sensory areas - Prevention of AMPA receptors into the dendritic spines: prevented the establishment of fear conditioning - Blocking LTP in the lateral amygdala: impaired the establishment of a conditioned emotional response - magnitude of the deficit was directly related to the decrease in postsynaptic AMPA receptors and the decrease in EPSPs LTP among glutamate synapses in the lateral amygdala plays a critical role in the establishment of conditioned emotional responses

Relational learning: role of the hippocampus - role of hippocampal neurogenesis in consolidation - long-term potentiation

Long-term potentiation plays a role in the incorporation of newborn neurons into circuits that store new memories. New neurons in the dentate gyrus participate in learning - Maturation of dendritic trees of newborn neurons and their integration into neural circuits of the hippocampus were accelerated when animals were trained on a spatial learning task - Infusion of a drug to block NMDA receptors (AP5) into the lateral ventricle did not affect the basal rate of neurogenesis - it did impair learning and prevented the normal learning-induced changes in neurogenesis from taking place

Long-term potentiation

Long-term potentiation: glutamatergic NMDA and AMPA receptors, pre and postsynaptic changes in the synapses of hippocampal cells

Relational learning: role of the hippocampus - reconsolidation of memories - well-consolidated relational memories

Long-term, well-consolidated relational memories are susceptible to disruption Process of reconsolidation makes it possible for established memories to be altered or attached to new information Events that interfere with consolidation also interfere with reconsolidation and can erase memories or make them inaccessible. Protein production is an important step in long-term potentiation and memory formation Blocking protein synthesis prevented the memory from going back to its original state.

Relational learning

Most memories of real objects and events are related to other memories Each of these memories can contain a series of events, complete with sights and sounds, that you will be able to recall in the proper sequence The neural circuits in the extrastriate cortex that recognize your friend's face are connected to circuits in many other parts of the brain, and these circuits are connected to many others

Amnesia: relational learning - spatial memory - hippocampus and caudate nucleus

Navigate through a computerized virtual-reality maze: learn the maze through distant spatial cues or through a series of turns. 1/2 spontaneously used spatial cues, and the other 1/2 spontaneously learned to make a sequence of specific turns at specific locations - Hippocampus was activated in participants who followed the spatial strategy - people who tended to follow a spatial strategy in a virtual maze had a larger-than-average hippocampus - Caudate nucleus was activated in participants who followed the response strategy - people who tended to follow a response strategy had a larger-than- average caudate nucleus Larger a person's caudate nucleus is (and the smaller a person's hippocampus is), the fewer errors that person made.

Types of memory: long-term memory - nondeclarative memories

Nondeclarative memory/implicit memory: memories that we are not necessarily conscious of Operate automatically - not require memorization or include facts or experiences. They control behaviors We do not need to be able to describe these activities in order to perform them. May not even be aware of them

Stimulus-response learning: reinforcement - detecting reinforcing stimuli reinformation

Occurs when neural circuits detect a reinforcing stimulus and cause the activation of dopaminergic neurons in the ventral tegmental area A stimulus that serves as a reinforcer in one situation may not in another - Activation depends on the state of the animal or the environment the stimuli occur in Reinforcement system are activated by unexpected reinforcing stimuli - Reinforcing stimulus does not occur when it is expected - activity of dopaminergic neurons suddenly decreases Activation of the dopaminergic neurons of the VTA communicate to other circuits in the brain that an event related to a potentially reinforcing stimulus has occurred - If the delivery of the reinforcer is already expected --> there is nothing needed to be learned Anticipation of a reinforcing stimulus increases the activation of the ventral tegmentum and some of its projection regions (nucleus accumbens) in humans

Long-term potentiation: role of synaptic changes - protein synthesis - long-lasting LTP - PKM-zeta

PKM-zeta: several important roles related to LTP - helps move AMPA receptors to the terminal membrane, and it remains active to perpetuate this contribution to LTP through a positive feedback loop Long-lasting activity of PKM-zeta may be the critical component that allows memories to last a lifetime

Stimulus-response learning: reinforcement - role of dopamine in reinforcement - study with l-DOPA

People learned a vocabulary of artificial words Learning was gradual Groups: 1) Given l-DOPA 90 minutes before each session - l-DOPA is the precursor for dopamine 2) Given a placebo Results: - l-DOPA: learned the faster and remembered it better

Perceptual learning: role of the cortex - memory - visual memories

Perceptual learning: changes in synaptic connections in the extrastriate cortex that establish new neural circuits - Later: when the same stimulus is seen again and the same pattern of activity is transmitted to the cortex - these circuits become active again - this activity constitutes the recognition of the stimulus of the visual memory Activation of neural circuits in the sensory association cortex constitutes the "replay" of a perceptual memory

Stimulus-response learning: reinforcement - role of the prefrontal cortex

Prefrontal cortex provides an important input to the ventral tegmental area Terminal buttons connecting prefrontal cortex and VTA - Secrete glutamate and the activity of these synapses makes dopaminergic neurons in the ventral tegmental area fire in a bursting pattern - Greatly increases the amount of dopamine they secrete in the nucleus accumbens Turns on the reinforcement mechanism when it determines that the ongoing behavior is bringing the organism nearer to its goals and that the present strategy is working

Motor learning: role of the cortex

Primary motor cortex: controls the movements of the body - organized somatotopically Several adjacent areas of cortex are critical in organizing complex, learned movements - Supplementary motor area: performing previously learned, automatic series of behaviors - Premotor cortex: motor learning and memory that is guided by sensory information - Ventral premotor cortex: home to mirror neurons that facilitate motor learning when observing another individual.

Overview of learning and memory: information processing model of memory

Provides an overall summary of the basic steps linking learning to memory Learning produces changes in the nervous system by encoding the new information to be learned Encoding process: - Consolidation: strengthens changes associated with the initial information that is learned, helping to make a more permanent change to the nervous system (i.e., a memory) - After consolidation --> memory is stored via these persistent changes in the nervous system - Retrieval: accessing and using the information stored in the neural changes that make up a memory to engage in a behavior Steps of learning and memory: Encoding (learning) —> consolidation (memory) —> storage (memory) —> retention (memory)

Amnesia: relational learning - spatial memory - CA1 neurons and intended locations

Rats in a spatial alternation task in a T-maze: rats enter the left and the right arms on alternate trials - when they did so, they received a piece of food in goal boxes located at the ends of the arms of the T - Corridors connecting the goal boxes led back to the stem of the T-maze, where the next trial began - Recorded from neurons in CA1 of the hippocampus and found that different cells fired when the rat was in different parts of the maze. - Two-thirds of the neurons fired differentially in the stem of the T on left-turn and right-turn trials - cells not only encoded the rat's location in the maze but also signaled whether the rat was going to turn right or turn left after it got to the choice point Activity of CA1 neurons encodes both the current location and the intended destination

Stimulus-response learning: reinforcement - role of dopamine in reinforcement

Reinforcing electrical stimulation of the medial forebrain bundle or ventral tegmental area/administration of cocaine or amphetamine: causes the release of dopamine in the nucleus accumbens Presence of natural reinforcers stimulates the release of dopamine in the nucleus accumbens Reinforcing events activate the human nucleus accumbens

Retaining perceptual information in short-term memory - extrastriate cortex - FFA, PPA

Retention of specific types of short-term visual memories involves activity of specific regions of the extrastriate cortex - Fusiform face area: ventral stream - recognition of faces - Parahippocampal place area: ventral stream - recognition of places Short-term memory for particular faces and places was associated with neural activity in two different regions of the ventral stream - Short-term memories of faces activated the fusiform face area - Short-term memories of places activated the parahippocampal place area.

Amnesia: relational learning - spatial memory - right hippocampal formation

Right hippocampal formation: active when a person is remembering or performing a navigational task - London taxi drivers describe the routes they would take in driving from one location to another - activation of the right hippocampal formation - The volume of the posterior hippocampus of London taxi drivers was larger than controls - Longer an individual taxi driver had spent in this occupation, the larger was the volume of the right posterior hippocampus T. T.: bilateral hippocampal damage. He had been a London cab driver for 40 years - Despite hippocampal damage - was able to navigate main city streets using memory that had been consolidated decades before - Ability to navigate side streets and non-main routes was impaired. Hippocampus is required for more detailed levels of spatial navigation

Retaining perceptual information in short-term memory - prefrontal cortex

Role of the prefrontal cortex in short-term memory: manipulate and organize to-be-remembered information, devise strategies for retrieval, and monitor the outcome of these processes Very sensitive to what it can possible learn in particular circumstances Damage to the left basal ganglia: difficulty filtering out irrelevant information Damage to the right prefrontal cortex: difficulty retaining more than a few pieces of information in short-term memory

Relational learning: role of the cortex

Semantic dementia: semantic information is lost but episodic memory for recent events can be spared Hippocampal formation and the limbic cortex of the medial temporal lobe: involved in the consolidation and retrieval of declarative memories (episodic and semantic) - Semantic memories appear to be stored in the neocortex (anterolateral temporal lobe) TMS of the left anterior temporal lobe produced the symptoms of semantic dementia - Difficulty naming pictures of objects and understanding the meanings of words - No trouble performing other, nonsemantic tasks

Amnesia: motor learning

Several studies have demonstrated motor learning in patients with anterograde amnesia Anterograde amnesia: learn a sequence of button presses in a serial reaction time task. They sat in front of a computer screen and watched an asterisk appear—apparently randomly—in one of four locations - The sequence of button presses specified by the moving asterisk was not random - Participants become faster and faster at this task - With amnesia learned this task as well as healthy volunteers

Amnesia: Korsakoff's syndrome

Severe anterograde amnesia: unable to form new memories, although they can still remember old ones. - Can converse normally and can remember events that happened long before their brain damage occurred Degenerations of the mammillary bodies, which are connected to the hippocampus Brain damage: result of chronic alcohol abuse B1 vitamin Alzheimer's disease: involves anterograde amnesia. - Similar to Korsakoff's syndrome

Long-term potentiation: role of synaptic changes - protein synthesis - early LTP overview

Short-term changes: NMDA is blocked by Mg2+ and is preventing Ca2+ from getting into the channel 1. AMPA receptors are near by 2. AMPA and NMDA is not activated at all 3. In the nucleus of a particular cell - it has a DNA and a PRKCZ gene which will create a messenger RNA which is going to leave through the nucleus of the cell and is going to go to all areas of the neuron - This messenger RNA - they are not doing anything and they degrade and go away - In each of the dendrite there is Pin 1 - inhibits the RNA from making any structural changes Long-term changes changes 1. Add gultuate to the AMPA which adds a lot of sodium to which removes Mg2+ and glutamate can interact with NMDA -The NMDA adds Ca2+ 2. Ca 2+ interacts with Cam-KII which will cause more Cam-KII to occur (positive feedback) 3. Because of the Ca2+ you can now move more AMPA receptors which will cause a larger potentiated response

Long-term potentiation: role of synaptic changes - protein synthesis - long-lasting LTP overview

Short-term changes: NMDA is blocked by Mg2+ and is preventing Ca2+ from getting into the channel 1. AMPA receptors are near by 2. AMPA and NMDA is not activated at all 3. In the nucleus of a particular cell - it has a DNA and a PRKCZ gene which will create a messenger RNA which is going to leave through the nucleus of the cell and is going to go to all areas of the neuron - This messenger RNA - they are not doing anything and they degrade and go away - In each of the dendrite there is Pin 1 - inhibits the RNA from making any structural changes Long-term changes changes 1. Add gultuate to the AMPA which adds a lot of sodium to which removes Mg2+ and glutamate can interact with NMDA -The NMDA adds Ca2+ 2. Ca 2+ interacts with Cam-KII which will cause more Cam-KII to occur (positive feedback) 3. Because of the Ca2+ you can now move more AMPA receptors which will cause a larger potentiated response 4. With additional Cam-KII it inhibits Pin 1 (which is another inhibition so it is a disinhibition) so at that particular dendritic spine - you can now allow the message for the protein PRKCZ 5. Will activate the trafficking protein - Will change the seize and shape of the synaptic space - Move AMPA receptors into synapses - This will only be seen in this particular location You can do a bunch of manipulation to change this system - Block the NMDA channel - Directly put in Ca2+ in the space - you were learn faster - Direcly inject Cam-KII: the synapse will learn as well - Put more Pin 1 - inhibit long-term potentiation

Long-term potentiation: role of NMDA receptors

Synaptic strengthening occurs when molecules of the neurotransmitter bind with postsynaptic receptors located in a dendritic spine that is already depolarized LTP requires two events: 1) Activation of synapses 2) Depolarization of the postsynaptic neuron NMDA receptor: glutamate receptor - Found in the hippocampal formation - especially in field CA1 - Controls a calcium ion channel - channel is normally blocked by a magnesium ion (Mg2+), which prevents calcium ions from entering the cell even when the receptor is stimulated by glutamate If the postsynaptic membrane is depolarized, the Mg2+ is ejected from the ion channel, and the channel is free to admit Ca2+ ions - Calcium ions enter the cells through the channels controlled by NMDA receptors only when glutamate is present and when the postsynaptic membrane is depolarized - Ion channel controlled by the NMDA receptor is a neurotransmitter- and voltage-dependent ion channel

Amnesia: perceptual learning

Test: recognize broken drawings - drawings are successively more complete - Participants are first shown the least complete set of each of 20 different drawings. If they do not recognize a figure, they are shown more complete sets until they identify it - One hour later, the participants are tested again for retention, starting with set I When H. M. was given this test and was retested an hour later, he showed considerable improvement. When he was retested four months later, he still showed this improvement - His performance was not as good as healthy volunteers - showed evidence of long-term retention.

Relational learning: role of the hippocampus - consolidation of memories

The hippocampal formation: process declarative memories are formed - Hippocampus promotes consolidation in the cortical areas 1) Hippocampus receives information about what is going on from the sensory and motor association cortexes and from some subcortical regions (basal ganglia and amygdala) 2) It processes this information 3) Through its efferent connections with these regions, modifies the memories that are being consolidated there, linking them together in ways that will permit us to remember the relationships among the elements of the memories (order in which events occurred, the context in which we perceived a particular item) Information —> short-term memories are rehearsed and encoded —> long-term memory storage

Types of memory: short-term memory

The second stage is short-term or working memory Only a small fraction of information passes from sensory memory to the short-term - If information is meaningful or salient enough it will move This stage is longer than sensory memory, but still limited to seconds or minutes Memory capacity of short-term memory is limited to a few items Length can be extended through rehearsal

Relational learning: role of the hippocampus - role of hippocampal neurogenesis in consolidation - The Morris water maze

The task requires rats to find a particular location in space solely by means of visual cues external to the apparatus The "maze" consists of a circular pool filled with a mixture of water and something to increase the opacity of the water - The water mixture hides the location of a small platform Experimenters put the rats into the water and let them swim until they find the hidden platform - They released the rats from a new position on each trial. After a few trials, the rats learned to swim directly to the hidden platform from wherever they were released The Morris water maze requires relational learning - Animals use information from the relative locations of stimuli located outside the maze Maze can be used for nonrelational, stimulus-response learning - Animals are always released at the same place, they learn to head in a particular direction

Types of memory: long-term memory

The third and final stage of memory Relatively permanent and can last for a range of time Short-term --> consolidated to long-term - Not all information makes it to long-term memory Long-term memories can be retrieved throughout a lifetime and strengthened with increased retrieval.

Stimulus-response learning: operant conditioning - basal ganglia - transcortical pathways

Transcortical connections are involved in the acquisition of declarative, episodic memories, complex behaviors that involve deliberation or instruction A memorized set of rules provides a script for us to follow At first, performing a behavior through observation or by following a set of rules is slow and awkward—we must ignore events that might distract us With practice - the behavior becomes much more fluid Finally we perform it without thinking and can easily do other things at the same time

Retaining perceptual information in short-term memory - extrastriate cortex - TMS

Transcranial magnetic stimulation (TMS) of the extrastriate cortex interferes with visual perception TMS: induce a weak electrical current in the brain that disrupts neural activity and interferes with the normal functions of the stimulated region Stimulating the ventral stream interfered with short-term memory for visual patterns Stimulating the dorsal stream interfered with short-term memory for location

Types of learning: stimulus-response learning - classical conditioning

Unimportant stimulus acquires the properties of an important one - association between two stimuli - There is no decision making - it is involuntary, reflexive A stimulus that previously had little effect on behavior becomes able to evoke a reflexive, species- typical behavior Unconditioned response (UR): occurs without any special training. Unconditioned stimulus (US): stimulus that produces the UR Conditioned stimulus elicits the conditioned response Amygdala, cerebellum - Basal ganglia is very important when creating the conditioned response

Perceptual learning: role of the cortex - memory - human studies

V5/MT/MST: essential role in perception of movement - photographs of athlete getting ready to throw a ball activated area MT/MST. - Very activated when you are watching someone do something. Learning occurred in V5 area: when you are watching a movement, you learn it and this area is activated when you watch someone do it or when you do the action

Perceptual learning: role of the cortex - learning - ventral and dorsal stream

Visual area: extrastriate cortical areas Ventral stream: object recognition "What" - Damage: disrupt the ability to discriminate among visual stimuli. These lesions impair the ability to perceive Dorsal stream: perception of the location of objects "Where"