METAPLASTICITY · Role of the Cav2.3 Voltage-gated Calcium Channel Subunit in Presynaptic Metaplasticity, and Hippocampal-dependent Learning and Memory
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-02-15 → 2006-08-14
- EU contribution
- €158,197
- Participants
- 1
- Scheme
- IIF
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Results in brief
Final Activity Report Summary - METAPLASTICITY (Role of the Cav2.3 Voltage-gated Calcium Channel Subunit in Presynaptic Metaplasticity, and Hippocampal-dependent Learning and Memory)
Most Central nervous system (CNS) synapses exhibit a striking potential for activity-dependent changes in synaptic efficacy, occurring either as long-term depression or Long-term potentiation (LTP). Since these lasting changes in synaptic transmission are candidate mechanisms for learning and memory, considerable attention has focussed on their molecular mechanisms. At many CNS synapses, LTP induction appears to require postsynaptic activation of N-methyl-d-aspartate-type glutamate receptors. In contrast, LTP induction at the hippocampal Mossy fibre (MF)-CA3 synapse, as well as at a number of other synapses, is thought to rely mainly on presynaptic mechanisms (see Castillo, Weisskopf and Nicoll, 1994, Neuron, 12:261-9). Previous work indicated that presynaptic Ca2+ influx is required for the induction of MF-LTP. However, the results of these earlier experiments did not allow for a determination of whether Ca2+ influx into the presynaptic neuron occurred at presynaptic versus somatic sites. We therefore developed a novel technique that allowed us to focally apply pharmacological agents to either the soma or the synapse of a neuron while recording MF field Excitatory postsynaptic potentials (fEPSPs). Using this technique, we were able to assess the role of somatic versus synaptic activity in MF-LTP during LTP induction by temporarily inactivating the soma or the synapse. We found that somatic activity was necessary for the induction of stable MF-LTP.
Data: CORDIS, © European Union
Project objective
There have been considerable advances in our knowledge of the mechanisms underlying NMDAR-dependent LTP and LTD. Less attention has been focused on a particularly intriguing finding: The capacity of synapses for plastic changes is itself plastic, that is, it is subject to considerable activity-dependent modulation.This higher-order plasticity, termed 'metaplasticity', may be crucial for maintaining plastic synapses within a dynamic functional range. It also provides an additional layer of complexity for synaptic integration of temporally spaced episodes of synaptic activity.Such metaplasticity has been observed experimentally as an inhibition of LTP or change in the frequency threshold between LTP and LTD by prior activation of NMDARs, or as a facilitation of LTP following either the activation of metabotropic glutamate receptors or the alteration of a behavioural state.Despite its functional importance, metaplasticity has been studied exclusively at synapses that require postsynaptic activation of NMDAR s for LTP and LTD induction, such as the Schaffer collateral-CA1 synapse within the hippocampus.In contrast, LTP induction at the hippocampal mossy fiber-CA3 synapse, as well as at a number of other synapses, is thought to rely mainly on presynaptic mechanisms Accordingly, the experiments in the current proposal will utilize the mossy fiber-CA3 synapse as a model to study metaplasticity of presynaptic LTP and LTD.We plan to study the following four phenomena:- priming-induced metaplasticity at the mossy-fiber CA3 synapse,- the Ca2+ influx pathways mediating presynaptic metaplasticity,- the signal transduction mechanisms underlying presynaptic metaplasticity, and- he role of metaplasticity in spatial learning and memory.These lines of research should clarify the mechanisms of presynaptic metaplasticity and also provide new insights into the role of metaplasticity in learning and memory.
Original text from CORDIS.
Participants
- FACULTY OF MEDICINE, UNIVERSITY OF BONN · BONNCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union