Lecture 13 Learning Memory PDF

RECAP of Attention and Working Memory Lectures Norepinephrine enhances alertness by increasing sensitivity of sensory neurons. Stimuli that are physically salient engage an automatic/involuntary process (pop-out effect) known as stimulus-driven or bottom-up attention. Goal-directed attention...

RECAP of Attention and Working Memory Lectures Norepinephrine enhances alertness by increasing sensitivity of sensory neurons. Stimuli that are physically salient engage an automatic/involuntary process (pop-out effect) known as stimulus-driven or bottom-up attention. Goal-directed attention (top down/serial) searches item-by-item to find the target. Damage to prefrontal & parietal regions can produce contralateral neglect (space/object). DLPFC and ACC are important in resolving attentional conflict (attentional control in Stroop). ADHD symptoms include: hyperactivity, inattention, impulsiveness. A predominant theory is a dopamine deficit hypothesis given that stimulants inhibit reuptake of dopamine to enhance DA activity and reduce symptoms.. Working memory - ability to maintain and manipulate information over short periods of time. Neural correlates of WM include the dorsolateral PFC and posterior parietal cortex. Dorsolateral PFC neurons remains active during the delay period when items are held in memory and involve recurrent projections. Sustained activity changes with development. When remember an item, activate the same brain regions as when we view an item (imagery). When switch focus between items in memory activate attentional frontoparietal regions. Long-term Learning and Memory  Memory of What is memory? Experiences The ability to retain and recall past events or information Are there different types of memories? Conscious memories: Episodic memory Semantic memory Implicit memories (not conscious): Skill memory Classical conditioning Principles of Behavioral Neuroscience, 1e Table 9-1  Memory of Experiences Episodic Memory The hippocampus is a brain region critical for the storage and retrieval of episodic memories. Principles of Behavioral Neuroscience, 1e Fig 9-3  Memory of Experiences Episodic Memory The role of the hippocampus in episodic memory based on the famous case of H.M., who underwent bilateral removal of the hippocampus to treat his severe epilepsy. Principles of Behavioral Neuroscience, 1e Fig 9-3 Adapted from Squire & Wixted, 2011, fig. 1  Memory of Experiences Loss of hippocampus After surgery removing the hippocampus, HM could no longer remember what he’d eaten for breakfast or recall having met any of the hospital staff. His episodic memory was impaired. He could no longer store memories of events that occurred after his surgery.  Memory of Experiences Loss of hippocampus: Working memory was intact: Patient could actively keep information in mind, such as the topic of a conversation, so long as he wasn’t distracted. However, he could not consolidate lasting memories, so the information was quickly lost.  Memory of Experiences Loss of hippocampus: Implicit memory was intact: Patient was able to acquire motor skills, such as learning to trace the outline of a shape while looking at the shape in a mirror. But because of his episodic memory loss, he believed each of his training sessions to be his first. “50 first dates” with Adam Sandler and Drew Barrymore  Memory of Anterograde and Experiences retrograde amnesia Anterograde amnesia is the inability to remember events that occurred after a brain injury. Damage to the hippocampus produces severe anterograde amnesia. Retrograde amnesia is the inability to recall events that occurred prior to a brain injury. Note: Hippocampal damage can cause partial retrograde amnesia. Long-held memories remain relatively intact. Principles of Behavioral Neuroscience, 1e Fig 9-4  Memory of Experiences According to the standard model of memory consolidation: The cortex and hippocampus interact to Memory involves: consolidate and recall memories. Encoding (initial learning of info) Note: The amygdala is thought to play a role in Consolidating (storing info), and what experiences are remembered long-term (emotional significance) Retrieving (accessing) info. However, when enough time (years) have passed after the event, the long-held memory is stored in the cortex, and no longer requires hippocampal involvement to retrieve the memory. This provides one of the leading explanations for why patients with hippocampal damage can continue to retrieve childhood memories.  Memory of Experiences Information Travels Through the Hippocampus The entorhinal cortex is the gateway to the hippocampus. Information passes through the entorhinal cortex before entering the hippocampus, and after leaving it. The hippocampus is comprised of the dentate gyrus (DG), area CA3, and area CA1. Principles of Behavioral Neuroscience, 1e Information flow through hippocampus Fig 9-6 dendateàCA3àCA1  Memory of Experiences How do we recognize distinct from similar memories? Dentate gyrus and CA3 thought to be involved in pattern separation (making similar memories distinct). While CA1 may be more important for pattern completion (re-establishing a past pattern of activity in response to partial or degraded input). Principles of Behavioral Neuroscience, 1e Information flow through hippocampus Fig 9-6 dentateàCA3àCA1  Memory of Experiences Memory of Familiar Places Hippocampus contains place cells, neurons typically from regions CA1 and CA3 that fire at a high rate when an animal is in a specific environmental location. Different portions of the environment cause different place cells to fire. The specific region of the environment that activates the Adapted from Lever et al., 2002 neuron is called the neuron’s place field. CA1 may continuously update representations of spatial experiences Principles of Behavioral Neuroscience, 1e to predict where the rat is going (pattern completion) while CA3 is encoding present location in the moment (pattern separation). Fig 9-9 From Matt Wilson’s Lab at MIT  Memory of Experiences Memory of Familiar Places The activity of several hippocampal place neurons together provides a cognitive map that allows the animal to track its location within a familiar environment. Principles of Behavioral Neuroscience, 1e Fig 9-9  Memory of Experiences Memory of Familiar People and Things In humans, the hippocampus and surrounding areas also contain neurons called concept neurons which represent information about specific people and things. Adapted from Quiroga, 2012 Neurons in occipital lobe area V1 respond selectively to lines of particular orientations, while neurons in the inferotemporal cortex (fusiform face area) (IT) respond to faces and not to other types of stimuli. Principles of Behavioral Neuroscience, 1e Concept neurons in the hippocampus fire selectively to the faces Fig 9-10 of particular people (Harris, Obama, Taylor Swift, Beyonce, Cher…) https://www.youtube.com/watch?v=JSLF0oAJJnw&t=30s Memories rewire the brain https://www.youtube.com/watch?v=JSLF0oAJJnw&t=30s  Principles of BehavioralNeural Plasticity 1e Neuroscience, Learning-related neural Fig 8-16 plasticity typically involves strengthening or weakening of synapses. Researchers studying plasticity can artificially strengthen synaptic connections. They begin by weakly stimulating a neuron (neuron 1) and observing the weak response in the receiving neuron (neuron 2). To begin with, the synaptic connection is weak. The synapse has few AMPA-type Two glutamate receptors: glutamate receptors AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor NMDA (N-methyl-D-aspartate) receptor  Neural Plasticity Principles of Behavioral Neuroscience, 1e Fig 8-16 In order to strengthen the synapse, the experimenter strongly activates neuron 1. This produces a large amount of glutamate release and causes the receiving neuron to fire.  Principles of BehavioralNeural Plasticity 1e Neuroscience, Fig 8-16 Finally, when the experimenter provides a weak stimulation of neuron 1 (identical to that introduced in the first step of the experiment), neuron 2 fires. Long-term strengthening of a synapse (shown in this example) is called long-term potentiation (LTP). Other procedures can lead to long-term weakening of synapses, called long-term depression (LTD).  Neural Plasticity Notice that in steps 1 and 3, 1. Before LTP Neuron 1 releases only a small amount of neurotransmitter. Before LTP, Neuron 2 hardly responds to the neurotransmitter. The neuron 2. LTP procedure (Strongly activate does not fire Neuron 1 so it activates neuron 2) After LTP, Neuron 2 responds strongly. It fires (black arrow along its axon). This strong response in neuron 2 is often the result of an 3. After LTP increase in AMPA receptors available for the neurotransmitter to bind to. Principles of Behavioral Neuroscience, 1e Fig 8-16  Memories rewire the The ability of the synapse brain between two neurons to change in strength is called: Synaptic plasticity! Example: 3 presynaptic neurons (1A, 1B, and 1C) send inputs to a postsynaptic neuron (2). Lets say there is strengthening of the synaptic connection between neurons 1B & 2. The swelling on the dendrite of synapse 2 represents an increase in the sensitivity or number of excitatory neurotransmitter Activation of neuron 1B is now more likely to activate neuron 2. receptors. Activation of neuron 1A or 1C is unlikely to activate neuron 2 because their synaptic connections to neuron 2 remain weak. Neurons that fire together wire together. Principles of Behavioral Neuroscience, 1e Fig 9-11  Memories rewire the brain LONG TERM POTENTIATION When a pre- and post-synaptic neuron fire one after the other several times the strength of the connection between them strengthens. This strengthening of the synapse can last hours, weeks, or, in some cases, months, and is therefore called long- term potentiation (LTP). The same amount of glutamate produces a larger depolarization of postsynaptic neuron (due to its increase in sensitivity or # of receptors). Principles of Behavioral Neuroscience, 1e Fig 9-12  Memories rewire the brain Glutamate Receptors AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Ion channels opens for Na+ : Sodium NMDA: N-methyl-D-aspartate receptor: ion channels open for Ca++ : Calcium The most studied form of LTP requires an interaction between two different types of glutamate receptor: AMPA-type: contains ion channel that opens for Na+ whenever glutamate attaches to the receptor’s binding site. NMDA-type: contains an ion channel, one that allows both Na+ and calcium ions (Ca++) to enter the neuron.  Memories rewire the brain When Glutamate (GLU) binds to an NMDA receptor, the ions cannot yet flow through the channel because a large magnesium ion (Mg++) is lodged in the channel blocking the ions from entering In order for Mg++ to move away, and for the channel to open, Glutamate must bind at the same time that the neuron is strongly depolarized (i.e., NMDA receptor’s ion channel is only open when neuron is activated/firing). So, if neuron 1 releases glutamate to neuron 2 and neuron 2 fires, the Na+ Sodium NMDA receptor on neuron 2 will Ca++ Calcium open and allow Na+ and Ca++ to Mg++ Magnesium Principles of Behavioral Neuroscience, 1e enter. Fig 9-14  Memories rewire the brain Entry of Ca++ sets in motion a series of events (gene expression and protein synthesis) inside neuron 2 that strengthen the synapse (i.e. INCREASE in the number or sensitivity of AMPA receptors, or an increase in future neurotransmitter release from the presynaptic neuron). Synapses can also weaken, or undergo long-term depression (LTD) (i.e., DECREASE in the number or sensitivity of AMPA receptors, or a decrease in future neurotransmitter release from the presynaptic neuron.) Principles of Behavioral Neuroscience, 1e Fig 9-14 Note: Structural changes in dendritic spines have been associated with LTP and LTD. Synaptic strength correlates with spine volume and the area of the postsynaptic density (orange). LTP can also lead to increase in new dendritic spines. Note: Toxic proteins believed to decrease LTP and increase LTD in Alzheimer’s disease. Christian Lüscher & Robert C. Malenka (2012) doi: 10.1101/cshperspect.a005710  LTP requires interaction between AMPA and NMDA glutamate receptors The NMDA receptor channel is blocked by Mg++ unless the postsynaptic neuron is depolarized (once depolarized the Mg++ is freed) As long as the NMDA channel is blocked CA++ cannot enter the neuron. Without entry of CA++ into the neuron the enzymes needed for plasticity are not activated, gene expression and protein synthesis are not triggered and more AMPA receptors cannot appear at the synapse. So for LTP to occur, both pre- and postsynaptic neurons need to be activated because the postsynaptic neuron must be depolarized when glutamate is released from the presynaptic neuron to fully relieve the Mg++ block of NMDA receptors so CA++ can enter. Christian Lüscher & Robert C. Malenka (2012) doi: 10.1101/cshperspect.a005710  You have a hippocampal concept neuron for Susan. You know Susan’s face but not her name. See her face and glutamate is released by “face” neuron crosses synapse and binds to AMPA receptors of postsynaptic “concept” neuron. No matter how many times you hear her name alone, the concept neuron won’t fire. BUT, when her name is presented with her face… BINGO! The presynaptic “name” neuron and postsynaptic “concept” neuron are active (depolarized) and Mg++ is freed (Yay!) so Ca++ can enter cell leading to changes in gene expression and protein synthesis that can increase the number of AMPA receptors and dendritic volume & spines! Now the name alone can activate the concept neuron in the future.  What happens when the hippocampus is lesioned during development? Based on nonhuman animal work, emergence of spatial memory is delayed and memory for object-space associations (episodes) is abolished. There are significant functional changes in the hippocampus by the first 2.5-3 years of life that may relate to infantile amnesia and again around puberty that may relate to memory for emotional contexts. With aging comes reduced neurogenesis and synaptic plasticity. Alzheimer’s disease thought to decrease LTP via toxic proteins.  Memories rewire the brain § Within the brain, some areas, including the hippocampus, new neurons are born even Learning and the birth during adulthood (adult neurogenesis). of new neurons § Learning and exploratory behavior can enhance the survival of newly born neurons within the hippocampus. § Prevention of neurogenesis within the hippocampus impairs learning.  Implicit Memory Skill learning § Practicing a skill can increase the size of the motor cortical region that participates in executing those movements. § Neuronal assemblies in the cortex are often comprised of neurons with strong excitatory connections to one another. § To perform a particular skill, the individual may activate particular neuronal assemblies within the motor cortex.  Skill learning Strengthening of learning A, B, C & D have through practice involves: strong connections to one another, but E is only weakly connected the inclusion of additional neurons into an assembly of neurons mediating task performance As more neurons are recruited into the skill-related neuronal assembly, the area of motor cortex activated during the skill expands. With practice E now forms strong connections with other members of the assembly (A, B, C, D). Principles of Behavioral Neuroscience, 1e Fig 9-16  Skill Automaticity of Well- learning Learned Behaviors PFC is highly active during early stages of learning a motor skill. As a motor skill becomes automatized, activity shifts to the premotor and primary motor cortices, and to basal ganglia circuits which include the striatum, that is associated with habitual actions. Cerebellum is involved in refinement of skilled movements. It learns to predict outcomes of motor commands and Cerebellum generates a forward model (i.e., what will happen in the future). Principles of Behavioral Neuroscience, 1e. Fig 9-17 Three other forms of “Implicit” Learning Classical conditioning Eyeblink conditioning Habituation learning  Memory of Experiences Whenever an experience affects our behavior without conscious awareness we have formed an implicit memory (procedural memory and classical/Pavlovian conditioning). What is classical/Pavlovian conditioning? %!$%& © Robert Leighton/ Cartoon Stock Principles of Behavioral Neuroscience, 1e Fig 9-2  Pavlovian/Classical Conditioning Pavlov in 1935, by Mikhail Nesterov One of Pavlov's dogs with cannula to measure salivation Remember that saliva is needed to breakdown /dissolve food’s chemicals so they can move through the central pore in a taste bud and bind to taste receptors (and also for digestion). Pavlovian/Classical Conditioning UCS Unconditioned stimulus UCR Unconditioned response Pavlovian/Claasical Conditioning Neutral stimulus Pavlovian/Classical Conditioning Repeated pairing of neutral stimulus (bell) and unconditioned stimulus(food)  Pavlovian/Classical Conditioning UCS Unconditioned stimulus UCR Unconditioned response CS Conditioned stimulus CR Conditioned response Neutral stimulus (bell before paired with food) Can we condition a cat? BoB the Cat (she, her, hers) Pavlovian/classical conditioning is different from instrumental learning Pavlovian/classical conditioning (passive) is different from instrumental learning (active) Pavlovian/classical conditioning (passive) is different from instrumental learning (active) Pavlovian/classical Instrumental Classical /Pavlovian Instrumental (passive learning) (active learning) Aversive (Cued-Fear) Classical Conditioning Classical Fear Learning Pair tone with a light foot shock repeatedly. Cued Fear Classical Conditioning Cued Fear Classical Fear Learning Pair tone with a light foot Then examine how much the shock repeatedly. animal freezes to the tone. Cued-Fear Classical Conditioning in Human Fear Learning Measure Fear Response Pair a colored square Examine Galvanic skin with a loud noise or shock conductance response (SCR) to paired square vs unpaired square Cued Fear § In cued fear conditioning, a subject learns that a learning conditioned stimulus (CS) such as a tone, (Classical Conditioning) signals the onset of an aversive (painful or unpleasant) unconditioned stimulus (US), such as a mild electric shock to the foot. § When the CS has been associated with the aversive US, presentation of the CS alone can produce a conditioned fear response (CR). § Fear learning depends importantly upon the amygdala.  Fear learning Threatening stimuli (shock) activate the basolateral amygdala, which in turn activates the central amygdala. Activity of neurons in the central amygdala generate a fear response, for they activate fear circuitry responsible for: freezing of limb movements sympathetic nervous system activation increased vigilance. Together, outputs from the central amygdala give rise to much of what we describe as fear. FEAR! Principles of Behavioral Neuroscience, 1e Fig 9-18  Fear learning Before the pairings of the CS (say, a tone) and shock, the tone CS is unable to activate the basolateral amygdala, and therefore cannot produce activation of the central amygdala and the fear circuitry. It is only through the repeated pairings of tone and shock that the tone can activate the lateral amygdala which produces activation of the central amygdala and fear circuitry. Principles of Behavioral Neuroscience, 1e Fig 9-19 Eyeblink § The cerebellum plays an important role in learning to respond quickly to environmental Conditioning events. § When a conditioned stimulus (tone), signals the onset of an air puff to the eye, subjects will learn to blink the eyes in response to the conditioned stimulus (tone). § This allows the individual to blink before the annoying air puff arrives. § The cerebellum is key to learning this kind of rapid behavioral response to environmental events.  Eyeblink conditioning Eyeblink conditioning Before conditioning, an air puff to the eye activates the cerebellum and generates an eyeblink. However, the tone (neutral stimulus) fails to activate the cerebellum, and produces no eyeblink. After tone-air puff conditioning, the connection between the tone input and the cerebellum strengthens. This allows the tone to produce an eyeblink before the air puff arrives. Principles of Behavioral Neuroscience, 1e Fig 9-20 Learning in simple organisms Some neuroscientists study learning in very simple organisms, such as the snail, because they have so few neurons that it is possible to track changes in all of the animal’s neurons during learning. Aplysia, sea snails, show some of the same simple forms of learning seen in humans. © 2005, Wägele & Klussmann-Kolb  Learning in simple organisms Habituation in Aplysia Habituation is learning to ignore a sensory event that is repeated many times without consequence. The Aplysia habituates to repeated touch to part of its body. When the Aplysia receives a touch near its gill, a sensory neuron fires and releases a large amount of excitatory neurotransmitter (glutatmate) which in turn activates a motor neuron causing its gill to withdraw. However, after repeated touch, the sensory neuron releases only a small amount of glutamate, leading to little response in the motor neuron, and little or no withdrawal of the Principles of Behavioral Neuroscience, 1e gill. Fig 9-21  RECAP Explicit memory includes episodic and semantic memories. Lesions of hippocampus result in intact WM, implicit memory and even LTM for information learned before the lesion, but failure to form new long-term memories (anterograde amnesia). Retrograde amnesia- can’t recall events before injury. Information flow is through hippocampus dentate -> CA3 -> CA1 Hippocampal place cells fire at high rate when animal is in specific location Concept neurons fire to specific specific people (Jennifer Aniston) and things. Long term potentiation (LTP) is a processing involving persistent strengthening of synapses that leads to long-lasting increase in signal transmission. For LTP to occur, both pre- and postsynaptic neurons need to be activated at the same time because the postsynaptic neuron must be depolarized when glutamate is released from the presynaptic neuron to free the Mg++ blocking NMDA receptors so CA++ can enter and faciliate changes in neuroplasticty through gene expression and protein synthesis that trigger more AMPA receptors at the synapse and increased volume and number of dendritic spines..  RECAP Implicit memory includes procedural/skill memories and classical conditioning. The prefrontal cortex becomes highly active during early stages of procedural/skill learning. As skill becomes automatized activity shifts to premotor and primary motor cortices and basal ganglia circuits. Classical conditioning (appetitive & aversive) involves the passive association of a neutral stimulus (bell, tone) and unconditioned stimulus (food, shock) with repeated pairings so that the neutral stimulus elicits a conditioned response (e.g. salivation, freezing) and is now a conditioned stimulus. Threatening stimuli activate the lateral amygdala , which in turn activates the central amygdala generating a fear response through the autonomic NS (sympathetic) resulting in freezing and increased vigilance. Eye blink conditioning The cerebellum plays an important role in learning to respond quickly to environmental events. Habituation is learning to ignore a sensory event that is repeated many times without consequence. The Aplysia habituates to repeated touch to part of its body.