CH 12: Learning and Memory

stages of LTP

- Early Long Term Potentiation (E-LTP) 1. membrane depolarization 2. release of glutamate 3. activation of NMDA receptors 4. entry of calcium ions (Ca2+) 5. activation of enzymes such as CaM-KII 6. movement of AMPA receptors into the postsynaptic membrane - Long-lasting Long Term Potentiation (L-LTP) * requires protein synthesis and occurs within one hour of the establishment of E-LTP * drugs that blocked protein synthesis, also prevented L-LTP * if the drugs were administered before, during, or immediately after a burst of electrical stimulation was delivered E-LTP occurred, but L-LTP didn't (meaning it only lasted a few hours) * if the drugs were administered an hour after the synapses had been stimulated, L-LTP occurred (it lasted more than a few hours)

CaM-KII

- a calcium dependent enzyme found in dendritic spines, inactive until a Ca2+ ion binds with it and activates it - plays a critical role in LTP - a study found that LTP could not be established in the CA1 field of hippocampal slices taken from mutated mice that could not produce the CaM-KII enzyme - accumulates in postsynaptic dendritic spines during LTP

dendritic spikes

- action potentials that occur in the dendrites of some types of pyramidal cells (pyramid shaped neurons) in the CA1 field of the hippocampal formation - have very high threshold of excitation and only occur when an action potential is fired in the axon of pyramidal cells - the backwash (motion of receding waves) of depolarization across the cell body triggers a dendritic spike *** whenever the axon of a pyramidal cell fires, all of its dendritic spines become depolarized too ***

AMPA receptors

- also found in the dendritic spines of CA1 pyramidal cell in the hippocampal formation - controls sodium (Na-) channels that when activated by glutamate produce EPSPs in the membrane of the dendritic spine - larger excitatory postsynaptic potentials (EPSPs) can be caused when a greater amount of AMPA receptors are activated by the release of glutamate from the terminal buttons (makes the synapses stronger)

population ESPS

- an extracellular measurement of the excitatory postsynaptic potentials (EPSP) produced by the synapses of the perforant path axons with the granule cells in the dentate gyrus (represents the EPSPs of a population of neurons) - size of the first population of EPSP indicates the strength of the synaptic connections before LTP has taken place - we know LTP has occurred if the response (population EPSP) is greater than it was before the burst of pulses was delivered

AMPA receptors in LTP

- an individual synapse can be strengthened by the insertion of additional AMPA receptors into the postsynaptic membrane of the dendritic spine - the establishment of LTP causes AMPA receptors from adjacent nonsynaptic regions of the dendrites to move to the postsynaptic membrane of the dendritic spines - AMPA receptors move into the postsynaptic membrane due to the entrance of calcium ions into the dendritic spine, given that Ca2+ is a secondary messenger that triggers certain biochemical processes and activates several enzymes (including CaM-KII)

human anterograde amnesia

- anterograde amnesia refers to the difficulty in forming new memories and recalling events that occurred after the brain damage - people affected by it can still remember everything they learned before the accidents - pure anterograde amnesia is rare, given that it is almost usually accompanied by some form of retrograde amnesia - basic abilities of perceptual, stimulus-response, and motor learning are intact, but complex relational learning is gone

anatomy of anterograde amnesia

- caused by damage to the hippocampus or to regions in the brain that supply its inputs or receive its outputs - Hippocampal formation consists of: * dentate gyrus * CA fields of the hippocampus * subiculum (and its subregions) - most important are for information input to the hippocampus is the entorhinal cortex * neurons in the entorhinal cortex send axons that terminate in the dentate gyrus, CA1, and CA3 * entorhinal cortex receives input from 1. amygdala, 2. various regions of the limbic cortex, and 3. all association regions of the neocortex ** either directly or indirectly through: perirhinal cortex and the parahippocampal cortex - outputs from the hippocampal system come primarily from: * field CA1 and the subiculum * which are relayed back through the entorhinal, perirhinal, and parahippocampal cortex to the same regions of the association cortex that provide inputs

role of the basal ganglia in instrumental conditioning

- circuits responsible for instrumental conditioning begin in various regions of the sensory association cortex (where perception takes place) and end in the motor association cortex of the frontal lobe (which controls movement) - two major pathways between the sensory association cortex and the motor association cortex - direct transcortical connection (connections from one area of the cerebral cortex to another) * involved in the acquisition of episodic memories * involved in the acquisition of complex behaviors that involve deliberation or instructions (e.g., learning to drive a car) ** learning new complex behaviors requires a lot of transcortical activity in the beginning (thinking, planning, recalling instructions) and thus we cannot respond to other stimuli ** with practice, the behavior becomes more fluid and automatic and is then "transferred" to basal ganglia network - connections via the basal ganglia and thalamus ** at first (when learning complex behaviors) the basal ganglia is "passive observer" receiving information of the stimuli present and the responses we are making ** after several repetitions, basal ganglia learns what to do and eventually takes over most of the details of the process leaving the transcortical circuits free to do something else 1. the neostriatum (caudate nucleus and putamen) receives sensory information from all regions of the cerebral cortex, plus information from the frontal lobes about movements that are planned or actually in progress 2. the output of the neostriatum are sent to the globus pallidus (another structure in the basal ganglia) 3. output from the globus pallidum is sent to the frontal cortex: premotor and supplementary motor cortex (plans for movements are made) and to the primary motor cortex (movements are executed)

lesions in areas of the brain involved in visual perception

- damage to the inferior temporal cortex (the end of the ventral stream) can disrupt the ability to discriminate among stimuli * can impair the ability to perceive (and thus recognize) * disrupt people's memory of the visual properties of familiar stimuli

functions of the reinforcing system

- detect the presence of a reinforcing stimulus * reinforcement occurs when neural circuits detect a reinforcing stimulus which activate dopaminergic neurons in the VTA - strengthen the connections between the neurons that detect the discriminative stimulus and the neurons that produce the instrumental response * when the brain's reinforcing mechanisms are activated by a stimulus, the link between the discriminating stimulus and the instrumental response is strengthened

semantic dementia

- different from anterograde amnesia * semantic information is lost, but episodic memory for recent events can be spared

lesions to the basal ganglia

- disrupt instrumental conditioning but don't affect other types of learning

types of declarative memory

- episodic memories * involves context, and it is specific to a time and place * information on when and under what conditions an episode occurred, and the order in which the events of the episode took place * episodic memories must be learned all at once - semantic memories * involve facts and general information * doesn't include information about the context in which the facts were learned * less specific than episodic memories * semantic memories can be acquired gradually, over time >> episodic and semantic memories are consolidated and retrieved by the hippocampus, limbic cortex, and the medial temporal lobe * but semantic appear to be stored in the neocortex

reconsolidation of memories

- established and consolidated memories can be altered or connected to newer memories - reconsolidation: consolidation of a memory after the original memory was consolidated * can be triggered by a reminder or experiencing the original stimulus * provide the means for modifying existing memories - physiological processes similar to original consolidation - re-experiencing a stimulus makes established memories labile (easily altered) - things that interfere with consolidation can interfere with reconsolidation

Hebb Rule

- explains how neurons are changed by experience in a way that causes changes in behavior - "if a synapse repeatedly becomes active at about the same time that the postsynaptic neuron fires, changes will take place in the estructure or chemistry of the synapse that will strengthen it" - WHAT FIRES TOGETHER, WIRES TOGETHER

NMDA receptors

- found in the hippocampal formation, especially in field CA1 and it is activated by N-methyl-D-aspartate (an agonist that mimics glutamate) - controls a calcium ion (Ca2+) channel (a neurotransmitter and voltage dependent ion channel) and it's blocked by magnesium ions (Mg2+) which prevent calcium from entering the cell even when the receptor is activated by glutamate - if the postsynaptic membrane is depolarized, Mg2+ is ejected from the ion channel and Ca2+ is free to enter the cell - Ca2+ can only enter the cell if glutamate activates the receptor and the postsynaptic membrane is depolarized to allow free passage

role of the hippocampal formation in consolidation of declarative memory

- hippocampus receives information about what's going on from: * the sensory and motor association cortex * subcortical regions (amygdala and basal ganglia) - processes this information - through efferent connections (going out) with these regions, modifies memories being consolidated there * links memories together so we can remember the relationships among elements of the memories - without the hippocampus we would have * individual, isolated memories * w/out the linkage that makes it possible to remember episodes and context - different role in recalling new and old memories * retrieval of most recent memories caused the greatest activation of the hippocampus * retrieval of oldest memories caused the least activation of the hippocampus *** opposite effect in frontal cortex (greatest activity = oldest memories /least activity = youngest memories) ***

nondeclarative (implicit) memory

- instances of perceptual, stimulus-response, and motor learning that we are not necessarily conscious of - appear to operate automatically, they do not require deliberate attempts on the part of the learner to memorize something - they don't include facts or experiences, instead, they control behaviors

instrumental (operant) conditioning

- involves behaviors that have been learned, it is the association between a stimulus and a response - it allows an organism to adjust its behavior based on the consequences that follow it - favorable consequences (reinforcing stimuli) tend to stimulate the behavior (behavior occurs more frequently) - unfavorable consequences (punishing stimuli) tend to reduce the behavior (behavior occurs less frequently)

relational learning

- involves learning the relationship among individual stimuli - episodic learning: remembering sequences of events, not only remember each individual event, but also remember the order in which they happened

hippocampal formation and its role in LTP

- it is a specialized region of the limbic cortex located in the temporal lobe - has a complex 3D shape - primary input to it comes from the entorhinal cortex - axons of neurons from the entorhinal cortex pass through the perforant path and form synapses with the granule cells of the dentate gyrus - a stimulating electrode is placed in the perforant path and a recording electrode is placed in the dentate gyrus (near the granule cells) - a single pulse of electrical stimulation is delivered to the perforant path and then the resulting population ESPS is recorded in the dentate gyrus

classical conditioning

- learning to associate two stimuli to a response Ex: puff of air (unconditional stimulus US because it elicits a response) makes eye blink (unconditional response UR - because it occurs w/out any training); pair a tone (neutral stimulus because it doesn't elicit any response) with the puff of air and after a few tries the eye blinks when the person hears the tone; tone (conditional stimulus CS - because it elicits the same response after conditioning), eye blink (conditional response CR - because it is elicited by the CS) *** LTP in the lateral amygdala, mediated by NMDA receptors and maintained by PKM-zeta, plays a critical role in establishing a conditioned emotional response, if blocked, fear learning is inhibited ***

long-term potentiation

- long-term synaptic changes responsible for learning can be induced by electrical stimulation of circuits within the hippocampal formation - intense electrical stimulation of axons leading from the entorhinal cortex to the dentate gyrus cause long term increase in the magnitude of excitatory postsynaptic potential in the postsynaptic neurons (long-term potentiation) - LTP can be induced by stimulating axons in the perforant path with a burst of approximately 100 pulses of electrical stimulation, delivered within a few seconds - can be produced in may places inside the brain and it can last for months - LTP can follow Hebb's rule: when weak and strong synapses to a single neuron are stimulated at approximately the same time, the weak synapse becomes strengthened (associative LTP) - a series of pulses all delivered in one burst at a high rate will produce LTP, but the same number of pulses given at a slow rate will not produce LTP - synaptic strengthening is more likely to occur when neurotransmitters bind with postsynaptic receptors located in an already depolarized dendritic spine *** LTP requires activation of synapses and depolarization of the postsynaptic neuron *** - LTP can altere synaptic structure (enlarge thin spines into fatter, mushroom-shaped spines) and create new dendritic spines (after 15-19h the new spines formed synaptic connections with the terminal buttons of nearby axons)

long-term depression

- low-frequency stimulation of the synaptic inputs to a cell decreases their strength - LTD occurs if the synaptic inputs are activated when the postsynaptic membrane is either weakly depolarized or hyperpolarized - LTD involves a decrease in the number of AMPA receptors in the dendritic spines (AMPA receptors removed from spines into vesicles)

declarative (explicit) memory

- memories that are explicitly available to conscious recollection as facts, events, or specific stimuli - memory of events and facts that we can think and talk about - but they are not just verbal memories (e.g., birthdays are declarative memories but we usually remember them as movie sequences)

PKM-zeta in LTP

- once the dendritic spine is depolarized and glutamate is released by the terminal buttons, NMDA receptors open to allow Ca2+ passage - Ca2+ activates several enzymes, including CaM-KII - CaM-KII binds to Pin1 and deactivates it - this allows the conversion from PKM-zeta mRNA to PKM-zeta protein to take place - PKM-zeta protein stimulates AMPA receptors to move to the postsynaptic membrane of the dendritic spine, which produces the first stage of LTP (Early LTP) - PKM-zeta protein starts a positive feedback loop which allows it to bind and deactivate Pin1 ensuring its own synthesis (and making the CaM-KII and other enzymes that originally deactivated Pin1 no longer needed) - the self-sustaining synthesis of PKM-zeta makes the second stage of LTP possible (Long-lasting LTP)

Korsakoff's syndrome

- one of the most severe symptoms is anterograde amnesia * the brain damage that causes Korsakoff's syndrome is usually a result of chronic alcohol abuse - confabulation: describe fictitious events when asked about an even that occurred recently * can be a mix of events that really occurred, or can be completely imaginary - caused by the bilateral removal of the medial temporal lobe

memory

- physically change the structure of the nervous system by altering neural circuits involved in perceiving, performing, thinking, and planning - short-term: stores limited amount of information, temporarily - long-term: stores large amounts of information, relatively permanent *** sensory information enters short-term memory, rehearsal keeps it there, and eventually, the information makes its way to long-term memory ***

relational learning in animals

- place cells: neurons that activate or fire at high rates when animal is in a certain location in the environment * they encode not only the animal's current location, but also, where they intend to go next

perceptual learning (vision)

- primary visual cortex receives information receive information from the lateral geniculate nucleus of the thalamus - after the first level of analysis, the information is sent to the extrastriate cortex (surrounding the primary visual cortex - striate cortex) - after second level of analysis (particular attributes of the visual scene such as form, color, and movement), subregions of the extrastriate cortex send the results of their analysis to the next level of the visual association cortex (divided into two "streams") - the ventral stream (continues ventrally into the inferior temporal cortex) is involved with object recognition. the "WHAT" - the dorsal stream (continues dorsally into the posterior parietal cortex) is involved with the perception of the location of objects. the "WHERE"

H.M. (famous case study)

- received a bilateral medial temporal lobectomy as a last resort in order to treat his severe epilepsy - caused damage to hippocampus * 3 general conclusions about the hippocampus 1. not the location of long-term memories, nor necessary for its retrieval 2. not the location of immediate (short-term) memories 3. is involved in converting immediate (short-term) memories into long-term memories *** this process is known as consolidation ***

spatial memory

- requires the hippocampus and relational learning * lesions disrupts ability to keep track of and remember spatial locations - anterograde amnesiacs cannot consolidate information on the * location of rooms, buildings, roads, etc... * location of important items on the environment

human retrograde amnesia

- retrograde amnesia refers to the inability to recall events that happened before the brain damage

NMDA receptors in LTP

- the entry of Ca2+ through the ion channel controlled by NMDA receptors is essential for LTP - AP5, drugs that blocks NMDA receptors and prevents Ca2+ from entering the cell, therefore preventing the establishment of LTP - if weak synapses are active by themselves, nothing will happen because the membrane of the dendritic spine does not depolarize sufficiently for Ca2+ channels controlled by NMDA receptors to open - if the activity of strong synapses located somewhere else on the postsynaptic cell have caused the cell to fire, then a dendritic spike will depolarize the postsynaptic membrane enough for Ca2+ to enter through the ion channel controlled by NMDA receptors

motor learning

- the establishment of changes within motor systems, but cannot occur without sensory guidance from the environment Ex: dancing involves feedback from the joints, muscles, vestibular apparatus, and eyes, and contact between the feet and floor - new behaviors: the more novel the behavior, the more neural circuits in the motor system of the brain must be modified

perceptual learning

- the establishment of changes within the sensory systems of the brain - is the ability to recognize things, not what to do when they are present * learning to recognize new stimuli or learning to recognize variances in familiar stimuli - identify and categorize objects and situations - all of the sensory systems are capable of engaging in perceptual learning - accomplished by changes in synaptic connections in the sensory association cortex that establishes new neural circuits * learning to associate visual stimuli involves changes in the visual association cortex * learning to associate auditory stimuli involves changes in the auditory association cortex)

Stimulus-response learning

- the establishment of connections between the sensory systems and motor systems - learning to perform certain behaviors after certain stimulus are presented - involves the establishment of connections between circuits involved in perception and movement - classical conditioning and instrumental (operant) conditioning

PKM-zeta

- the gene responsible for the production of PKM-zeta is always active * transcribes the DNA of the gene into messenger RNA (mRNA), which is then transported near the dendritic spines - the Pin1 enzyme inhibits the translation of PKM-zeta mRNA into PKM-zeta protein - PKM-zeta is both necessary and sufficient for L-LTP to occur * infusion of PKM-zeta in CA1 pyramidal cells produces LTP even without stimulation of NMDA receptors or the entry of calcium ions * blocking PKM-zeta production abolished both L-LTP and some forms of long-term memory

How does instrumental conditioning affect the brain?

- the process of reinforcement strengthens a connection between neural circuits involved in perception and movement * the brain contains reinforcing mechanisms that control this process

How does classical conditioning affect the brain?

- the unconditional stimulus (puff of air) is first detected by a neuron in the somatosensory system - the conditional stimulus (tone) is detected by a neuron in the auditory system - the response (eye blink) is controlled by a neuron in the motor system *this process actually involves thousands of neurons* 1. the CS (tone) by itself doesn't elicit a response because the synapse connecting the neuron in the auditory system with the neuron in the motor system is weak * the excitatory postsynaptic potential (EPSP) produced in the dendrites of the motor neuron by the action potential when it reaches the terminal buttons of synapse T (tone) is too weak to make the neuron fire 2. the US (puff of air) by itself does evoke a response because the synapse connecting the neuron in the somatosensory system and the motor system is strong 3. to condition a response, we present the CS (tone) quickly followed by the US (puff of air), after pairing both stimuli several times, the CS will elicit a response

neural circuits involved in reinforcement

- when a response leads to favorable outcomes * reinforcing mechanisms in the brain become active * the establishment of synaptic changes is facilitated - activity of dopaminergic neurons is very important in reinforcement - mesolimbic system of dopaminergic neurons begins in the ventral tegmental area (VTA) of the midbrain * projects to the amygdala, hippocampus, and nucleus accumbens (NAC) ** NAC neurons project to the ventral part of the basal ganglia involved in learning ** reinforcing electrical stimulation of the medial forebrain bundle (MFB) or the VTA, or administration of cocaine or amphetamine causes the release of dopamine in the NAC, also caused in the presence of natural reinforcers (sex, water, food) - mesocortical system of dopaminergic neurons also begins in the VTA * projects to the prefrontal cortex, limbic cortex, and the hippocampus

how does Hebb rule apply to classical conditioning

- when the CS tone is presented, weak synapse T (tone) becomes active - if the US (puff of air) is presented immediately after, then strong synapse P (puff of air) becomes active and causes the neuron to fire - the act of firing strengthens any synapse that was active (e.g., synapse T) with the motor neuron which elicits the response (eye blink) - after several pairings, and several strengthening, synapse T becomes strong enough to cause the motor neuron to fire and therefore elicit the response by itself

Learning

experiences that change our nervous system and therefore our behavior