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Long term potentiation
 

Long term potentiation

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    Long term potentiation Long term potentiation Presentation Transcript

    • 1 LONG-TERM POTENTIATION
    • Kolb, An Introduction to Brain and Behavior, Second Edition – Chapter 5 Role of Synapses in Learning and Memory • Habituation Response • Sensitization Response • Long-Term Potentiation and Associative Learning • Learning at the Synapse • Focus on New Research: Dendritic Spines, Small but Mighty
    • • The Nature of Learning – Learning: • The process by which experiences change our nervous system and hence our behaviors • Memories are reconstructed recollections of events and other episodes encountered during our lives – Types of learning (the basics): • Classical conditioning: – A learning procedure in which when a stimulus that initially produced no particular response is followed several times by an unconditioned stimulus that produces a defensive or appetitive response • Instrumental learning: – A learning procedure whereby the effects of a particular behavior in a particular situation increase (reinforce) or decrease (punish) the probability of the behavior • Perceptual learning: – Learning to recognize a particular stimulus • Motor learning: – Learning to perform a particular motor task (writing)
    • • The Nature of Learning – Learning: • The process by which experiences change our nervous system and hence our behaviors. – Perceptual learning: • Learning to recognize a particular stimulus. 4 Associative Learning Linkage of two or more unrelated stimuli to elicit a behavioral response
    • • The Nature of Learning – Classical conditioning: • A learning procedure; when a stimulus that initially produces no particular response is followed several times by an unconditioned stimulus that produces a defensive or appetitive response. 5
    • • The Nature of Learning – Instrumental learning: • A learning procedure whereby the effects of a particular behavior in a particular situation increase (reinforce) or decrease (punish) the probability of the behavior; also called operant conditioning. 6
    • 7
    • • The Nature of Learning – Reinforcing stimulus: • An appetitive stimulus that follows a particular behavior and thus makes the behavior become more frequent. – Punishing stimulus: • An aversive stimulus that follows a particular behavior and thus makes the behavior become less frequent. – Motor learning: • Learning to make a new response. 8
    • 9 In – Integrate -- Out
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Long-term potentiation: • A long-term increase in the excitability of a neuron to a particular synaptic input caused by repeated high- frequency activity of that input. 10
    • • The Nature of Learning • For decades, researchers have been trying to determine how learning is recorded and stored in the brain • There is no shortage of theories, but the most influential (and most likely correct) was proposed by Donald Hebb over 50 years ago • Hebb’s rule: – The cellular basis of learning involves strengthening of a synapse that is repeatedly active when a postsynaptic neuron fires – Through repeated pairing, there will be structural and chemical changes resulting in strengthening of active synapses forming a stronger circuit – This is a form of long term potentiation Fire together = Wire together
    • • The Nature of Learning –Hebb rule: • The hypothesis proposed by Donald Hebb that the cellular basis of learning involves strengthening of a synapse that is repeatedly active when the postsynaptic neuron fires. 12
    • Kolb & Whishaw, An Introduction to Brain and Behavior, Second Edition - Role of Synapses in Learning and Memory Associative Learning • A strong burst of electrical stimulation applied to the presynaptic neuron produces an increase in the amplitude of the EPSP in the postsynaptic neuron • First recorded in the hippocampus by Bliss and Lømø in 1973 – Field Potential: • EPSPs from many neurons; recorded with extracellular electrodes
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Hippocampal formation: • A forebrain structure of the temporal lobe, constituting an important part of the limbic system; includes the hippocampus proper (Ammon’s horn), dentate gyrus, and subiculum. 14
    • Classical Long Term Potentiation • Classical or nonassociative long-term potentiation: – A long-term increase in the excitability of a neuron to a particular synaptic input caused by repeated high- frequency activity of that input – Usually modeled through two neurons, a presynaptic neuron’s repeatedly providing high frequency of activity to another neuron • LTP occurs throughout the brain, but a high concentration of LTP occurs in the hippocampus and is believed to play a role in learning and memories 13.6
    • • Induction of Long-Term Potentiation (LTP) • Hippocampal formation: – A forebrain structure of the temporal lobe, constituting an important part of the limbic system – Hippocampus includes the dentate gyrus, CA fields, and the subiculum • Dentate gyrus: Part of the hippocampal formation that receives inputs from the entorhinal cortex and projects to the CA3 field of the hippocampus – Perforant path: The system of axons that travel from the entorhinal cortex to the dentate gyrus – Granule cells: Receives input from the perforant path and sends axons to the field CA3 of the hippocampus
    • 17Copyright © 2004 Allyn and Bacon
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Entorhinal cortex: • A region of the limbic cortex that provides the major source of input to the hippocampal formation. – Granule cell: • A small, granular cell; those found in the dentate gyrus send axons to the field CA3 of the hippocampus. 18
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Dentate gyrus: • Part of the hippocampal formation; receives inputs from the entorhinal cortex and projects to the CA3 field of the hippocampus. – Perforant path: • The system of axons that travel from cells in the entorhinal cortex to the dentate gyrus of the hippocampal formation. 19
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Field CA3: • Part of the hippocampus; receives inputs from the dentate gyrus and projects to field CA3. – Pyramidal cell: • A category of large neurons with a pyramidal shape; found in the cerebral cortex and Ammon’s horn of the hippocampal formation. 20
    • • Learning and Synaptic Plasticity – Induction of Long-Term Potentiation – Field CA1: • Part of the hippocampus; receives inputs from field CA3 and projects out of the hippocampal formation via the subiculum. – Population EPSP: • An evoked potential that represents the EPSPs of a population of neurons. 21
    • Hippocampus Dentate gyrus CA3 CA1 Entorhinal CortexSubiculu m
    • 23
    • • Induction of Long-Term Potentiation • If the cells of the perforant path are stimulated with rapid bursts of electricity, there will be stronger and stronger EPSPs recorded in the granule cells of the dentate gyrus – This is evidence of LTP – This heightening of activity lasts over time (up to several months)
    • 25Copyright © 2004 Allyn and Bacon
    • Associative Long Term Potentiation •With this type of LTP, a weak burst of electrical stimulation paired with a strong burst of electrical stimulation will result in an increase in the strength of the electrical stimulation by the weak input over time •This is consistent with Hebb’s rule
    • • Role of NMDA Receptors in LTP – Non-associative LTP requires a high frequency rates of input to produce LTP delivered over a short period of time to dendritic spines of postsynaptic neurons • The rapid rate of stimulation results in increases postsynaptic membrane depolarization because the previous EPSP has not dissipated, resulting in a summation effect of EPSP – For LTP to occur, the postsynaptic cell must be depolarized and receiving excitatory input from presynaptic cells • The reason both these events must be occurring simultaneously is due to the complex nature of the receptor protein that plays a role in LTP, the NMDA receptor – NMDA receptor: • A specialized ionotropic glutamate receptor that controls a calcium channel (Ca2+ ) • Normally, NMDA receptors are blocked by a Mg2+ ion which prevents Ca2+ from entering the channel, even in the presence of the glutamate on the receptor • However, when the cell is slightly depolarized Mg2+ is ejected AND Ca2+ can enter the cell resulting in depolarization and strengthening of a synaptic connection (or LTP)
    • • Learning and Synaptic Plasticity – Role of NMDA Receptors – Associative long-term potentiation: • A long-term potentiation in which concurrent stimulation of weak and strong synapses to a given neuron strengthens the weak one. – NMDA receptor: • A specialized ionotropic glutamate receptor that controls a calcium channel that is normally blocked by Mg2 ions; involved in long-term potentiation. 28
    • 29
    • Kolb & Whishaw, An Introduction to Brain and Behavior, Second Edition -
    • 31 13.2
    • 32 • Neurotransmitters and Neuromodulators – Amino Acids – Glutamate – Glutamate: • An amino acid; the most important excitatory neurotransmitter in the brain. – NMDA:_______________? • A drug that serves as a noradrenergic and serotonergic agonist, also known as “ecstasy”; has excitatory and hallucinogenic effects.
    • 33 • Neurotransmitters and Neuromodulators – Amino Acids – Glutamate – NMDA receptor: • A specialized ionotropic glutamate receptor that controls a calcium channel that is normally blocked by Mg2+ ions; has several other binding sites. – AMPA receptor: • An ionotropic glutamate receptor that controls a sodium channel; stimulated by AMPA and blocked by CNQX; the most common glutamate receptor. AMPA receptor: An ionotropic glutamate receptor that controls a sodium channel; when it’s open, it produces EPSPs
    • 34 Copyright © 2004 Allyn and Bacon 13.1
    • 36 • Neurotransmitters and Neuromodulators – Amino Acids – Glutamate – Kainate receptor: • An ionotropic glutamate receptor that controls a sodium channel; stimulated by kainic acid and blocked by CNQX. – Metabotropic glutamate receptor: • A category of metabotropic receptors sensitive to glutamate. – AP5: • A drug that blocks the glutamate binding site on NMDA receptors AP5: 2-Amino-5-phosphonopentanoate; a drug that blocks NMDA receptors.
    • 37 Dendritic spike: An action potential that occurs in the dendrite of some types of pyramidal cells.
    • • Learning and Synaptic Plasticity – Role of NMDA Receptors – Dendritic spike: • An action potential that occurs in the dendrite of some types of pyramidal cells. 38
    • 39Copyright © 2004 Allyn and Bacon 13.3
    • 40
    • 41 Ready to Learn!
    • • Presynaptic Facilitation of LTP – Research believe that presynaptic facilitation is also required for LTP • This may result in an increased release of glutamate from presynaptic cells – Nictric oxide (NO) is a molecule created from a naturally occurring amino acid present in the brain • NO is used as a messenger in the circulatory system and other parts of the body • It is a short acting messenger that is quickly degraded in the brain – Drugs blocking NO seem to prevent development of LTP. Other evidence suggesting NO may be involved in LTP: • NO is synthesized in cells containing NMDA receptors • NO is synthesized in hippocampal cells, such as the dentate gyrus, CA1, and CA3 – In a way that has not yet been determined, NO causes an increase release of glutamate – Finally, LTP requires synthesis of proteins, which is believed to take place in dendritic spines much like it takes place in and around the cell nucleus • Second Messenger – Activated by a neurotransmitter (the first messenger) – A chemical that carries a message to initiate a biochemical process • Examples – Alter ion flow in a membrane channel – Formation of new ion channels – Production of new proteins
    • • Learning and Synaptic Plasticity – Mechanisms of Synaptic Plasticity – CaM-KII: • Type II calcium-calmodulin kinase, an enzyme that must be activated by calcium; may play a role in the establishment of long-term potentiation. – Nitric oxide synthase: • An enzyme responsible for the production of nitric oxide. 43
    • 13.4
    • Kolb & Whishaw, An Introduction to Brain and Behavior, Second Edition - Role of Synapses in Learning and Memory Learning at the Synapse • What neural processes underlie the persistent, long-term changes of learning? – Ca++ enters postsynaptic neuron and activates a second messenger (e.g., cyclic AMP) – cAMP alters gene expression in nucleus, which physically alters synapse: • Structural changes in the synapse – Dendritic spines • Formation or loss of synapses
    • • Learning and Synaptic Plasticity – Long-term Depression – Long-term depression: • A long-term decrease in the excitability of a neuron to a particular synaptic input caused by stimulation of the terminal button while the postsynaptic membrane is hyperpolarized. 46 Long-term depression: A long-term decrease in the excitability of a neuron to a particular synaptic input caused by stimulation of the terminal button while the postsynaptic membrane is weakly depolarized or is hyperpolarized Also results in a decrease of AMPA receptors found in the cell membrane
    • Kolb & Whishaw, An Introduction to Brain and Behavior, Second Edition - Role of Synapses in Learning and Memory Neurochemistry of LTP • Long-Term Depression – Another form of synaptic plasticity – Neuron becomes less active in response to repeated stimulation – Involves NMDA receptors – Requires Ca++ entry: • Decreased responsiveness of AMPA receptors • Decreased numbers of AMPA receptors AMPA
    • 48