Week 4 Lectures 3 PDF

morphologies, which may contribute to the disease state Understand that several lines of evidence indicate that neuronal wiring may be altered in the brains of individuals with SCZ Describe that a number of genetic factors associated with SCZ encode for proteins found at synapses Underst...

morphologies, which may contribute to the disease state Understand that several lines of evidence indicate that neuronal wiring may be altered in the brains of individuals with SCZ Describe that a number of genetic factors associated with SCZ encode for proteins found at synapses Understand that it is possible to model the role of synaptic proteins to gain insight into how dysregulation of these proteins may result in altered dendritic spine number, and therefore altered neuronal wiring By the end of Topic 3 you will be able to: Describe the way that synapses are modified by activity and experience Understand how spontaneous activity segregates the brain’s response to sensory stimuli Understand how sensory experience integrates the brain’s response to sensory stimuli Understand how sensory deprivation re-balances the brain’s response to sensory stimuli Understand how inhibition shapes critical periods for development Appreciate how scientific insight into the impact of activity, experience and deprivation on the brain informs us about the causes of neurodevelopmental disorders  05/08/2019 Brain memory. How INSTITUTE OF PSYCHIATRY, - stores potentiation Home PSYCHOLOGY & NEUROSCIENCE Clouy term Professor Module: Peter Giese Biological Foundations of Mental Health Topic 1: Week 4: Learning, memory and Biological basis of learning, memory and cognition synaptic plasticity Part 1 of 4 Topic list This week, we will be looking at the following topics: Topic 1: Learning, memory and synaptic plasticity Topic 2: From the dynamic synapse to synaptopathies Topic 3: The effects of activity, experience and deprivation on the nervous system Click Next to continue Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 2 of 13 1  05/08/2019 Part 1 Part 1 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 3 of 13 Introduction *How the brain stores and forms memory Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 4 of 13 2  05/08/2019 Part 1: Overview Synaptic plasticity Neurons are connected by synapses Synaptic plasticity: very important for learning and memory long term potentiation (LTP) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 5 of 13 Definition of synaptic plasticity Synaptic plasticity: can increase and/or decrease Long term potentiation (LTP) History-dependent change in synaptic transmission can be short-lasting or long-lasting Long term depression (LTD) -- Short term potentiation Plasticity of excitatory synaptic transmission Short term depression - Presynaptic Presynaptic Presynaptic terminal terminal terminal Glutamate Glutamate Glutamate - - Mg2+ LTP LTD NMDA NMDA NMDA AMPA receptor receptor receptor receptor Ca2+ Ca2+ Ca2+ LTP: Long term potentiation Postsynaptic Postsynaptic Postsynaptic LTD: Long term depression terminal terminal terminal Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 6 of 13 3  05/08/2019 Measurement of synaptic plasticity pp: perforant path The famous case of the H.M. patient mf: mossy fibers Patient who suffered from severe epilepsy Sch: Schaffer collaterals Method: Surgeons in the 1950s decided to remove the focus of the epilepsy by lesioning the Hippocampus area of the brain that produces it, which revelat includes the hippocampus. Outcome: The lesion worked for the treatment of stimulation recording epilepsy but resulted in severe memory impairment. Conclusion: The hippocampus is important for learning and memory, particularly for declarative declarative Sch CA1 memory. * dedaitement memory pp mf How do you study synaptic plasticity in the hippocampus? CA3 By using an electric stimulation electrode that simulates and records synaptic currents. Cerates a potentials O’Keefe and Nadel (1978) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 7 of 13 CA2 electrode requi. m also recoding red Different forms of synaptic plasticity Netan EPSP: Excitatory postsynaptic potential (measure of excitatory synaptic transmission) Difference between STP and LTP: A higher frequency stimulation is required Short term potentiation (STP) Long term potentiation (LTP) Long term depression (LTD) EPSP EPSP EPSP 100% 100% 100% high frequency Time high frequency Time low frequency Time stimulation stimulation stimulation Duration: Duration: Normally lasts for about 30 minutes Can last for several hours or even up to a year in vivo Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 8 of 13 4  05/08/2019 Properties of LTP (1) Long-term potentiation was thought to be a mechanism of 300 induction maintenance information storage in the brain. 250 EPSP (% of baseline) 200 150 Short term potentiation PTPPost-tetanic potentiation (PTP) 100 PTP 50 100 Hz stimulation S 0 wow -30 -15 0 15 30 45 60 75 90 105 120 135 150 165 180 Time (min) 100 Hz stimulation = 100 stimuli in one second Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 9 of 13 Properties of LTP (2) Long lasting Input specific Cooperativity Associativity (long lasting enhancement of (specific to the activated (need a threshold stimulation to (applies to long term potentiation synaptic transmission) synapses only – doesn’t affect induce long term potentiation – only at two different synapses – neighbouring synapses) signals of relevance induce long neighbouring synapse experience) term potentiation) Strong Strong input (S) Active (A) input Weak input Inactive (I) Weak input (W) I W A S Before After Before After Before After Before After Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 10 of 13 5  05/08/2019 ~Stil Properties of LTP (3) rape A synaptic model of memory: Long-term potentiation in the hippocampus EPSP: Excitatory postsynaptic potential (measure of excitatory synaptic transmission) Weak stimulation S1 S2 Strong stimulation FEPSPs: Field excitatory postsynaptic potentials corci - Principle of associativity: S1 electrode weak stimulation + strong stimulation = production of LTP EPSP Principle of cooperativity: This stimulation did not reach the required threshold to induce LTP Pavlovian conditioning (Pavlov's dog): Principle of associative learning Production of long lasting synaptic transmission S2 electrode Transient increase in synaptic transmission (PTP and STP) EPSP followed by LTP that is long lasting and stable Input specific phenomenon: Only occurs in the S2 pathway and not in S1 (within the same timeframe) Bliss and Collingridge (1993) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 11 of 13 Part 1: Summary Phenomenon of long-term potentiation In the next part, we will explore: the underlying molecular mechanisms of LTP its role in learning and memory Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 12 of 13 6  05/08/2019 End of part 1 End of part 1 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 13 of 13 7  05/08/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Peter Giese Biological Foundations of Mental Health Topic 1: Week 4: Learning, memory and Biological basis of learning, memory and cognition synaptic plasticity Part 2 of 4 Part 2 Part 2 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 2 of 10 1  05/08/2019 Part 2: Overview In part two, we will look at long-term potentiation in more detail. We will also talk about molecular mechanisms that underlie the induction, consolidation and the maintenance of LTP. Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 3 of 10 Molecular mechanisms of LTP induction Presynaptic membrane Glutamatergic Enhancing synoptic transmission in the postsynaptic synaptic transmission membrane can be done through: could livity Glutamate phosphorylation of the AMPA receptors P ~ Mg2+ - increasing the number of AMPA receptors Firepolarizatio ↳untungitis Mg2+ - Na+ Ca2+ release retrograde signalling Trana AMPA NMDA receptor P receptor Enhanced *. Depolarises membrane Ca2+ S Endosomes Bind to calmodulin Comia Protein kinase activation Gene expression changes in Synaptic changes the nucleus or translation of mRNA at the synapse Long term potentiation is induced Signalling cascade at the postsynaptic site. C required Synthesis of Postsynaptic membrane new proteins Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 4 of 10 Y retrograde signaling. this ex. Nitric oxide indus 2  05/08/2019 The role of CAMKII in LTP production CaMKII: calcium calmodulin- dependent kinase II phosphorylation P of the kinase CaMKII seems to be a critical enzyme for the induction of long-term potentiation. Lisman et al. (2012) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 5 of 10 The late phase of LTP Long-term potentiation varies in terms of its duration. long LTP needs to undergo a protein synthesis-dependent process to be lost-lasting 300 250 EPSP (% of baseline) Late LTP or L-LTP: 200 Terms introduced by Eric Kandel. 150 Late-LTP (L-LTP) Nobel Laureate Requires gene transcription and protein synthesis - 100 Long lasting forms of LTP require protein synthesis and gene transcription. 50 100 Hz stimulation The proteins required for the Tget induction of LTP also contribute 0 to its long lasting nature. -30 -15 0 15 30 45 60 75 90 105 120 135 150 165 180 Time (min) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 6 of 10 Laskohy Lo 3  05/08/2019 Synaptic tagging (synaptic capture) andin aaudi How can these new synthesised proteins be delivered specifically to the synapses A B - undergoing long term potentiation? Once the signal reaches the nucleus, it results 1 in gene expression, followed by mRNA translation and protein synthesis 2 1 nucleus Importins are thought to be important - 2 molecules for gene expression 3 These newly synthesised proteins can only be 3 taken up by tetanised synapses 4 The strong tetanisation induces a molecular 4 change, a so called tag setting, that captures PRP 5 Late phase LTP Early phase LTP transforms into late phase LTP 6 due to it coinciding in time with a strong 6 ~ tetanisation 5 PRP: Plasticity-related protein Redondo and Morris (2011) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 7 of 10 &P heieeerlizs LTP maintenance LTP induction LTP consolidation LTP maintenance Requires NMDA Requires protein It has been suggested that this receptors and synthesis that is taken is mediated by the local CaMKII up by activated translation of the PKMζ kinase. synapses only PKMζ: This mechanism only lasts for as long as PKMζ Lacks a regulatory is around (a few hours to a day at most) domain. Therefore its catalytic domain is active all the time once it has How is long term potentiation kept over a lifetime? been produced. Once PKMζ is turned over, it is replaced Castime. by newly synthesised PKMζ. S When late phase LTP is An active form of PKMζ should always be induced, the repression is present in the synapses that maintain LTP. relieved and PKMζ mRNA can be translated Sacktor (2011) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 8 of 10 effectivein 4  05/08/2019 Part 2: Summary Molecular principles of Research is undergoing on LTP induction the importance of these proteins in late phase LTP Consolidation of early LTP The importance of PKMζ in into late phase LTP via the maintenance of LTP synthesis of new proteins Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 9 of 10 End of part 2 End of part 2 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 10 of 10 5  12/06/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Peter Giese Biological Foundations of Mental Health Topic 1: Week 4: Learning, memory and Biological basis of learning, memory and cognition synaptic plasticity Part 3 of 4 Part 3 Part 3 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 2 of 11 1  12/06/2019 Part 3: Overview Hippocampal memory tasks Studies have shown that some of the patients treated for epilepsy with surgical ablation of the hippocampus have reported suffering from severe memory impairment. The hippocampus is very Further animal experiments are important for learning needed to understand the exact memory in humans. consequences of lesioning the hippocampus. In this part, we will focus on mice studies that have been used to address the issue of long term potentiation and memory. Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 3 of 11 General points about memory Different forms of memory can be distinguished by: John O'Keefe American-British neuroscientist, University College London - Time scale: Brain areas: Discovered the importance of the hippocampus in the process of short-term hippocampus - making a spatial map of the - long-term cerebellum environment, a so called * ‘cognitive map’. working memory Long term potentiation is thought The hippocampus is to be an important mechanism in important for declarative - > facls. long term memory storage. memories in humans. - C Declarative * Studies in mice have shown the memories are not hippocampus to be of particular applicable to mice. importance in - spatial and contextual memory. - Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 4 of 11 2  12/06/2019 mis n ~ Water maze Spatial memory study conducted by Richard Morris Insertion point Insertion = point X - Invisible Invisible platform platform Learning outcome: Learning phases: * Testing the learning strategy: To be able to remember the 1: Try to climb out of the pool Remove the platform and location of the platform. observe if the animal searches 2: Explore the environment by swimming around randomly the area where it used to be 3: Learn to use the platform as a resting spot located in. Procedure strategies ultimately lead to spatial learning. 4: Develop a strategy (‘procedures’) to locate the platform Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 5 of 11 Example of learning in the water maze Latency (seconds) The mutant mice did The training curve alone does not show the same not suffice as an indicative of improvement impaired spatial learning in the mutant mice or of spatial The wild type mice learning in the wild type mice. showed an improvement in learning over time Training sessions - Latency (seconds): The time the animal needs to reach the platform To get evidence for the performance of the wild type mice, we have to conduct a memory probe trial that indicates different strategies, such as: learning that there is no escape & Types of mice: T286A mutants, nonenriched (n=9) use of platform WT (wild type mice), nonenriched (n=9) strategy learning T286A mutants, nonenriched (n=12) WT (wild type mice), enriched (n=12) spatial strategy Need and Giese (2003) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 6 of 11 3  12/06/2019 Assessment of spatial memory in a probe trial nice Spatial memory probe trial (drug treated animal) Training quadrant The amount of time spent by the control mice in the training quadrant indicates: · a clear spatial bias spar evidence for spatial memory spatial mery biad wit The amount of time spent by the drug treated mice in the training quadrant indicates: a lack of spatial memory Morris et al. (1986) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 7 of 11 Passive avoidance (1) Single trial Lit Dark Passive avoidance task compartment compartment Can be learned in a single training trial. - This passive avoidance task requires the hippocampus. A lesion in the hippocampus would jeopardise the mouse’s association between the dark compartment and the foot shock. foot shock Presented Frodut Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 8 of 11 4  12/06/2019 Passive avoidance (2) One-trial learning task E Advantages: useful in the study of molecular and cellular processes because due to all animals learning at the same time more suitable in the study of learning and memory processes in comparison to the water maze due to the lack of - synchronization in animal behavior Smild - mutat easy to distinguish between short term memory (STM) and long term memory Typemac anime - (LTM) Cuddly da Irvine et al. (2005) Week 4 Biological basis of learning, memory and cognition Cay Weekplasticity Topic 1: Learning, memory and synaptic after training 2 – Lorem ipsum 9 of 11 Part 3: Summary = Behavioural testing of protocols *Long term potentiation measured in the What happens when the for assessing hippocampus - hippocampus is connected to induction of LTP is blocked? dependent memory hippocampus dependent memory tasks - Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 10 of 11 5  12/06/2019 End of part 3 End of part 3 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 11 of 11 6  12/06/2019 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Professor Module: Peter Giese Biological Foundations of Mental Health Topic 1: Week 4: Learning, memory and Biological basis of learning, memory and cognition synaptic plasticity Part 4 of 4 Part 4 Part 4 Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 2 of 22 1  12/06/2019 Part 4: Overview In this section, we will: discuss the importance of LTP in the LTP: hippocampus in learning and memory is connected to long learn about approaches to study lasting synaptic plasticity whether LTP is induced through is input specific training in a memory task 1s follows Hebb’s postulate (Hebbian theory) learn about methods that manipulate LTP and its impact on learning and memory Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 3 of 22 Is LTP a memory mechanism? (1) Donald Hebb Canadian psychologist The Organization of Behaviour, 1949 This book illustrates the principle of how Hebb thought neurons behave when an animal learns new information Dendrites Cell Body Neuron B “When an axon of neuron A … excite(s) neuron B and repeatedly or persistently takes part in firing it, some growth processes or metabolic changes take place in one or both neurons so that A’s Axon efficiency as one of the cells firing B is increased.” Synapse Neuron A Although LTP follows Hebb’s postulate, it is the synaptic - transmission - that is enhanced and not the firing. Hebb (1949) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 4 of 22 2  12/06/2019 Is LTP a memory mechanism? (2) Does such type of synaptic plasticity really exist in a behaving brain? Researchers have asked the following question: Can training in a hippocampus dependent memory task induce LTP? Passive avoidance task Lit Dark compartment compartment foot shock Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 5 of 22 Occurrence of LTP (1) ~ dectudeta Behaviour is used to induce LTP: Only a small set of synapses undergo LTP, hence the need for multiple electrodes to detect it. Inhibitory avoidance task 0 - - 0- Whitlock et al. (2006) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 6 of 22 3  12/06/2019 Occurrence of LTP (2) - No LTP was induced in the performance controls. LTP was induced only in animals trained in the inhibitory avoidance task, showing that behavioural training can induce LTP. - Whitlock et al. (2006) Learning induces long-term potentiation in the hippocampus - LTP occurs during memory formation. - Whitlock et al. (2006) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 7 of 22 Block of LTP correlates with impaired memory formation - The following experiments tested the impact of LTP manipulation on the water maze behaviour task. - Memory probe trial: Platform is removed Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 8 of 22 4  12/06/2019 Block of LTP and spatial memory - Spatial memory probe trial (drug treated animal) This study shows: - Training - drug treated animals have a random surge, indicating that they ↳ quadrant have no spatial memory = control animals show spatial memory awareness blocking the NMDA receptor impairs spatial learning - Important to note: - the drug dose in these experiments was relatively high, resulting in performance abnormalities amongst some of the animals blocking NMDA receptors not only blocks the induction of LTP => but also blocks long term depression AP5: NMDA receptor blocker L can't exchulle imp. Week 4 Biological basis of learning, memory and cognition LTDeP = impairs Topic 1: Learning, memory and synaptic Morris et al. (1986) Weekplasticity 2 – Lorem ipsum 9 of 22 leaving. - General strategy for gene targeting in mice LTP can be blocked by generating mutant mice. Whilst a limited number of drugs allow us to block particular molecules, genetics allow us to manipulate any gene of interest. In 2007, the Nobel Prize committee awarded the Nobel Prize Rationale: for gene targeting in manipulating the mouse genome. Impairment of the molecular process Impairment of LTP CRISPR/Cas Impairment of learning and memory Authors: Mario R. Capecchi Sir Martin J. Evans Oliver Smithies The Nobel Prize in Physiology or Medicine 2007 (2019) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 10 of 22 5  12/06/2019 Region-restricted knockout mice Susumu Tonegawa Nobel laureate Received the Nobel prize for his discovery of Conditional knock out antibody diversity. Method of study: Knock out an essential NMDA receptor subunit 1) (GluN1) exclusively in the hippocampus and study its impact. Result: Tonegawa succeeded in having a mutant mouse with an active Cre recombinase exclusively in the CA1 hippocampal area Knocking out the gene that encodes GluN1 blocks NMDA receptors GluN2 GluN1 Tsien et al. (1996) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 11 of 22 Region-restricted KOs Result: There was a lack of the NMDA subunit in the CA1 region Tsien et al. (1996) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 12 of 22 6  12/06/2019 Block of LTP and spatial memory Knocking out NMDA receptors in the CA1 area impairs spatial learning. The findings from this study are consistent with the ones where the pharmacological blockage of the NMDA receptors results in the blockage of spatial memory. However, NMDA receptors can also block long- term depression. Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 13 of 22 aCaMKII-T286A mutants CaM-dependent state 2+ - Ca regulatory domain CaM inactive 2+ + Ca Aeschati T286A CaM Kinase II: catalytic domain a calcium calmodulin- dependent kinase. CaM CaM 2+ - Ca 286 T P 286 T P active Autonomous state Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 14 of 22 7  12/06/2019 Genetic block of LTP in hippocampus These animals have severely impaired LTP in CA1 in the hippocampus. Finding: Autophosphorylation of CaMKII at threonine-286 is fundamentally important for the induction of LTP. Cooke et al. (2006) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 15 of 22 Impaired spatial learning and memory in T286A mutants Memory probe trial Finding: wild-type animals have a selective surge in the target mutants lack LTP induction and spatial memory, quadrant, while various mutants have a random surge, further strengthening the correlation between indicating no spatial memory in the latter LTP and memory Need and Giese (2003) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 16 of 22 8  12/06/2019 Block of LTP maintenance impairs established memory ZIP induced reversal of LTP ZIP induced loss of place avoidance memory D E Peptide that blocks protein kinase M zeta, important for the maintenance of LTP Finding: ZIP erased the memory in these animals and consequently also erased LTP. This shows the existence of a strong correlation between LTP and memory maintenance. Genamus. Pastalkova et al. (2006) Week 4 Biological basis of learning, memory and cognition Weekplasticity Topic 1: Learning, memory and synaptic 2 – Lorem ipsum 17 of 22 Lecture summary There is very strong evidence that LTP is a memory mechanism. It follows Hebb’s postulate. We have seen that: LTP can be induced by behavioural training blocking LTP induction seems to block spatial memory formation