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.
Field of science
- /natural sciences/biological sciences/neurobiology
Call for proposal
See other projects for this call