Lecture 17 - Cellular Learning and Memory PDF

Introduction to Behavioral Neuroscience PSYC 211 Lecture 17 of 24 – Cellular learning and memory Professor Jonathan Britt Questions? Concerns? Please write to [email protected] first part cellular learning of memory LEARNING & MEMORY Learning refers to the process by which experiences chang...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 17 of 24 – Cellular learning and memory Professor Jonathan Britt Questions? Concerns? Please write to [email protected] first part cellular learning of memory LEARNING & MEMORY Learning refers to the process by which experiences change our nervous system and hence our behavior. We refer to these changes as memories (memory traces or memory engrams). Memories can be transient or durable, explicit or implicit, personal or impersonal. Accessing memories is known as memory retrieval. acting on memory we learned The cellular basis of long-term memory is neuronal plasticity, which refers to the ability of the nervous system to change and adapt. we gonna look changes in neurons excitability how strong are the connections, the input coming when seizures neurons make new protein, read new genes … or alternative no physical change in the brain brain comes back still with long term memorythings changed neural plasticity always waves in neural activity maybe learning when change this wave become more complex, evolve but no actual physical change how do they change ? no new synapses which is true ? NEURONAL LEARNING & MEMORY To identify neuronal plasticity, researchers typically measure… 2 ways to measure neurons change how action potential likely is, when gets excitability income • Intrinsic excitability - the number of action potentials a neuron exhibits in response to an influx of positive current pretty generic form of learning and if stable always get same number of action potential in response if change can be less action potential or more can be a change in membrane potential, for ex more potassium leak channel more hyperpolorize so more input to spike ? • Synaptic strength - the amount of positive (or negative) current that enters the postsynaptic neuron when a presynaptic cell has an action potential.  A change in the strength of the synaptic connection between two neurons is called synaptic plasticity. we look at the size magnitude of this sinaptic response size of response wheter depolarization or hyper no matter size something about the synapse have changed MEASUREMENT OF INTRINSIC EXCITABILITY Intrinsic excitability is determined by the number and type of ion channels (leak channels and voltage-gated channels) expressed by the neuron. Action potentials elicited by a positive current injection record activity record voltage difference with outside and inside we can also inject current record membrane potential depolarize because gets positive current, so cell strike ? how active the neuron will be dependent of the channels it has how many, which … This cell is more excitable than the cell above. Texte Intracellular current injection If a neuron starts making fewer potassium leak channels, its resting membrane potential will be slightly depolarized, which means the neuron will be more excitable in general (i.e., it will exhibit more action potentials in response to the same excitatory synaptic input). SYNAPTIC PLASTICITY Synaptic plasticity refers to changes in the strength of the synaptic connection between two neurons. When a presynaptic cell releases neurotransmitter, how if response depo excitatory big or small is the postsynaptic we saything if deporalised enough first cell axon response (regardless of potential but if not enough whether it is depolarization or depoback it wont do, go to rest important not to hyperpolarization). induce action If the postsynaptic response is depolarization, we call it an EPSP (excitatory postsynaptic potential). potential here we need to make sure synapse low enough stimulate post synaptic cell so it has action potential measure what the second cell in response inhibitory = depo or hypo subthreshold EPSPs in recorded cell before and after synaptic strengthening synaps ebecome stronger bigger if more glutamate filled vesicles for ex can regulate how stronge that synapse is Electrical stimulation of nearby afferent axons when synapse stronger filling out post synaptic with receptors so dendritic spine gets bigger correlation between their size and size to postsynatic response if very big get split in two so 2 synapses Synaptic plasticity can involve pre- and postsynaptic changes. • On the presynaptic side, the amount of voltage-gated calcium channels on the presynaptic membrane influences how many vesicles will be released following an action potential. • On the postsynaptic side, the amount of neurotransmitter receptors influences the sensitivity of the postsynaptic cell to neurotransmitter release. NON-ASSOCIATIVE LEARNING: HABITUATION & SENSITIZATION ▪ The aplysia is an invertebrate sea slug with a simple nervous system (20,000 neurons). ▪ It has a large gill for respiration, and a siphon through which it expels water. ▪ If the siphon is lightly touched, the gill withdraws reflexively. protective ▪ Repeated light touching of the siphon will reduce the magnitude of this reflex until the Aplysia completely ignores light touches. slower and slower animal earn this touch not harmful ▪ This is an example of habituation - reduced physiological or behavioural responding to a repeated stimulus. yelow thing brings oxygen out of water the gill ▪ In contrast, in response to painful electrical shocks, the sea slug’s gill withdrawal reflex becomes stronger. Increased sensitivity to a stimulus is known as sensitization. HABITUATION OF APLYSIA GILL WITHDRAWAL REFLEX dissect animal die take some cell of animal but can survive for a while in special place activates touched sensitive sensory neurons activates axion potentials …. withdraw • Does the sensory neuron become less sensitive to touch? No, touch continues to cause the same amount of positive ions to enter the sensory neuron. still sensitive to touch • Has the excitability of the sensory neuron changed? Yes, fewer action potentials (1 vs 2) occur when the siphon touched after sameisamount of current tho habituation. more hyperpolarized so harder to spike sensory neuron motor and gill • Has the synaptic connection weakened between the sensory and motor neurons? Yes. postsynatic response changed      Less presynaptic vesicles docked? Vesicles have less glutamate in them? Fewer presynaptic voltage-gated calcium channels? Fewer postsynaptic glutamate receptors? Are postsynaptic glutamate receptors less sensitive to glutamate or do they not open as much or for as long as they did before habituation? • Has the motor neuron become less excitable? No, it spikes the same amount when depolarized. more hyperpolarized sensory neurons change • fewer or more voltage gadted calcium channels release less glutamate ?? all changes where in sensory neurons same excitability Has the synaptic connection weakened between the motor neuron and gill? No, the gill is as sensitive to an action potential in the motor neuron as before. so what tf happened mice rats i think anyway mammal NEURONAL LEARNING & MEMORY Cell excitability and synaptic strength can be directly we want to extract the brain fast enough so neurons measured in brain slice recordings. still alive like can still have action potential if cut part of dendritic spine cell like close in a way and survive so do not worry baby gurl so basically neurons small piece of what it used to be but still itself like has action potential synaptic inputs, makes proteins … even if some axon cut this is brain slice orange = axon terminal with vesicles of neurotransmitter, if axon potential release neuro in green part pgreen = dendrites, with have spine head neck and stuff size of synapses is not encoded into our genome, like this does not say this synapse should be strong or weak kinda random then evolve through experiences, some gets stronger other weaker mammal : how many neurotransmitter in postsynaptic spine, more strong, mainly So what can we do to change strengh of synapses ? SYNAPTIC PLASTICITY Long-term potentiation (LTP) Long-term increase in the strength of the connection between two neurons (i.e., increased synaptic strength). - Repeated high-frequency (tetanic) stimulation of the inputs to a neuron often induces LTP. Commonly used is 100 Hz stimulation for 1 second (repeated 4 times). - LTP is often initiated on the postsynaptic side (with more neurotransmitter receptors) but retrograde signaling of nitric oxide (NO) can drive presynaptic modifications (e.g., more vesicles of neurotransmitters). Long-term depression (LTD) Long-term decrease in the strength of the connection between two neurons (i.e., decreased synaptic strength). more than likestimulation 10 20 min - Persistent low-frequency of the inputs to a quiet neuron we can induce it by stimulating an axon, if stimulate axon one every 10 sec causes LTD. Commonly used is 1 Hz stimulation for 10 minutes. response stable but if in between repeatly do a high frequency stimulation, synapse stronger generally often - LTD is often initiated on the postsynaptic side (with less neurotransmitter receptors) but retrograde endocannabinoid signaling can drive presynaptic modifications (e.g., less calcium-influx per action potential). SYNAPTIC PLASTICITY Long-term potentiation (LTP) Long-term increase in the strength of the connection between two neurons (i.e., increased synaptic strength). - Repeated high-frequency (tetanic) stimulation of the inputs to a neuron often induces LTP. Commonly used is 100 Hz stimulation for 1 second (repeated 4 times). - LTP is often initiated on the postsynaptic side (with more neurotransmitter receptors) but retrograde signaling of nitric oxide (NO) can drive presynaptic modifications (e.g., more vesicles of neurotransmitters). Long-term depression (LTD) we can weaken synapse Long-term decrease in the strength of the connection between two neurons (i.e., decreased synaptic strength). - Persistent low-frequency stimulation of the inputs to a quiet neuron often causes LTD. Commonly used is 1 Hz stimulation for 10 minutes. - LTD is often initiated on the postsynaptic side (with less neurotransmitter receptors) but retrograde endocannabinoid signaling can drive presynaptic modifications (e.g., less calcium-influx per action potential). but what molecules involved to weaken or strong SYNAPTIC PLASTICITY: LTP & LTD • High frequency stimulation (~100 Hz) for 1 second, repeated a few times every 10 seconds often produces LTP. • The same number of stimulations delivered at a slow rate (1 Hz) over 5-10 minutes often produces the opposite effect: LTD. Why??? • It turns out that LTP and LTD are a function of the number of times the synapse was activated as well as whether the postsynaptic neuron fired at those precise times. what determines stronger or weaker is how many times activation how many times • For LTP to occur, the release of neurotransmitter must coincide with a substantial depolarization of the postsynaptic cell (normally associated with an action potential). or close to • High frequency axon stimulation often causes postsynaptic neurons to spike (summation of EPSPs brings the neuron across threshold). Low frequency stimulation on its own is often not sufficient to get a past threshold of hyperpolarization postsynaptic neuron to spike. stimulate like no time to come back to resting state was spiking when stimulation LONG-TERM POTENTIATION neurons constantly monitoring are these synapses helpful or not constantly change strengh or not to test role of hyper stimulate slowly but depola postsynaptic at the same time it actually stronger cell active while depolarization fire together wire together if synapse active everytime you are spiking, then good if active when no spiking, bad boo out - how often is it active - and wether depolarized or not is there molecule monitarising these two things > glutamate receptor called NMDA iotropic receptor positive, sodium comes in big pore bigger ion can get in like sodium a coincidence detector opens, magnesium tries to come in but cannot fit clog to pore no flow ? if cell deporalized to like -40 or more depo magnessium not as attracted to go through hug membrane less so flow throuhg this ion channel so flow only if depolarized enough so sensitive to presence of glutame (is it active) depolarization the 2 like flow calcium comes in key signal for synaptic strengh if can get in rush in because a lot outside amount of calcium in determines if strenghen or weaken so NMDA receptor massive role learning almost every glutamate synapse will have glutamate receptor and NMDA receptor who determine if stronger or weaker should 9t detects if depolarized and calcium comes in, amount of in determines if a little come = weaken lot = strenghten THE NMDA RECEPTOR NMDA receptors plays a large role in learning and memory. They are located in almost every glutamatergic synapse in the brain. ROLE OF NMDA RECEPTORS NMDA Glutamate receptor – A coincidence detector • The NMDA receptor is an ionotropic glutamate receptor that has a large ion pore. When the NMDA receptor binds glutamate and opens, magnesium ions (Mg2+) try to pass through its pore, but they get stuck in it and block all current flow. The Mg2+ blockage of the NMDA receptor only occurs when the membrane potential is below threshold (< -40mV), such as when the cell is at rest. • If the membrane is depolarized (i.e., more positive than -40 mV) because of other synaptic inputs, then Mg2+ ions will not try to enter though the NMDA receptor, and thus they won’t clog the pore. • So, current flow through the NMDA channel is gated by both glutamate and membrane voltage. Na+ and Ca2+ ions will enter a cell through NMDA receptors, but only when these receptors are bound to glutamate and Mg2+ is not clogging the pore. MECHANISMS OF SYNAPTIC PLASTICITY AMPA receptor 2 main glutamate receptors in the brain The glutamate receptor that mediates most excitatory fast synaptic currents in the brain. It is ionotropic and opens upon glutamate binding. It lets in sodium ions which cause EPSPs (excitatory postsynaptic potentials) that depolarizes neurons. Most glutamate synapses in the brain have AMPA and NMDA receptors. how many of these determine strengh of synapse more = stronger, what drives excitatory truc post potentials NMDA receptor Ionotropic glutamate receptor that only passes current upon glutamate binding when the membrane potential is slightly depolarized. If glutamate binds when the cell is hyperpolarized, the pore will get blocked by Mg2+. Open, unblocked NMDA receptors allow sodium and calcium ions through. CaMKII Type II calcium-calmodulin kinase. It is an enzyme that is activated by calcium influx through NMDA receptors. It plays a role in the intracellular signaling cascade that establishes long-term potentiation, by increasing the number of postsynaptic AMPA receptors (in excitatory glutamatergic all other synapses on postsynaptic size synapses). calcium binds to this strenghen or weaken synapse to can say make more or cell ampa LONG-TERM POTENTIATION cam measure these changes visually because stronger synapses are bigger pre gets big when post gets big here ? post stimulation after 2 hours boum bigger release more glutame ?? The strength of glutamate synapses strongly correlates with the size of the postsynaptic dendritic spine and the number of AMPA glutamate receptors in it. LTP can also be expressed through changes on the presynaptic side of things, but postsynaptic neurons often initiate the process. Many experiments suggest that nitric oxide (NO) can act as a retrograde messenger (released from postsynaptic membrane and detected by presynaptic membrane) to promote LTP. CLASSICAL CONDITIONING key experiment associative learning associate two things together learn the relationship eye blink closure response puff = blink, reflex blue cell synapse cause to blind when puff so orange fire after blue to blink if pair tone and puff, do both animal will close blink in anticipation of puff so assumption mauve connect to weak, if mauve has action potential orange will not so no blink but if as orange is active is also receive tone input, we have fire together wire together every time orange depo also gets tone input mauve active every time im depo so mauve usefull so synapse stronger SYNAPTIC PLASTICITY: LONG-TERM POTENTIATION Associative long-term potentiation slide before example pairing things The increase in synaptic strength that occurs in weak synapses when they are active right around the time when stronger inputs caused the postsynaptic neuron to spike. = Hebb’s rule Hypothesis proposed by Donald Hebb that the cellular basis of learning involves the strengthening of synaptic connections that are active when the postsynaptic neuron fires an action potential. This is known as: Fire together, wire together…more strongly than before. The synaptic connection does have to initially exist. everything is a bit wired together everyone kinda interconnected most synapses are weak so when cell together wire more strongly than before BRAIN SLICE LTP INDUCTION preparation for brain slice often study hypocampus stimulate axon activation depolarisation action potential maybe also stimulate from diff direction weak action which wont action potential but wtf i did not understand that TYPES OF LEARNING Perceptual learning Learning to recognize stimuli as distinct entities. Motor learning Learning to make skilled, choreographed movements. Procedural learning. Relational learning Learning relationships among individual stimuli. Stimulus-Stimulus learning. Stimulus– response learning Learning to perform a particular behavior when a particular stimulus is present. Includes classical and instrumental conditioning.