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Hippocampal mossy cell circuit plasticity: unconventional synaptic mechanisms and functional impact on seizures| title | Hippocampal mossy cell circuit plasticity: unconventional synaptic mechanisms and functional impact on seizures |
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| start_date | 2024/03/25 |
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| schedule | 14h |
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| online | yes |
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| visio | https://us06web.zoom.us/j/82114169177?pwd=aa14btakTK1kFxdOhaRLBNLYszvdOK.1 |
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| location_info | En visio |
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| summary | In the dentate gyrus (DG), the main input area of the hippocampus, granule cells (GCs) and mossy cells (MCs) form a recurrent excitatory circuit that is critically involved in DG function and epilepsy. However, how this circuit is regulated is poorly understood. A long-term change in neurotransmitter release is a widely expressed mechanism controlling neural circuits in the mammalian brain. Interestingly, robust long-lasting increase in glutamate probability of release occurs in activity-dependent manner at MC-GC synapses. Thus, mediating a robust activity-dependent long-term potentiation (MC-GC LTP). In this study, we sought to determine the molecular mechanism underlying MC-GC LTP and the role of such plasticity in experimental seizures. Remarkably, recent evidence revealed that MC-GC LTP can be induced in vivo with optogenetic stimulation, by enriched environment exposure, and following experimental epileptic activity. In addition, we found that uncontrolled strengthening of MC-GC transmission promotes seizures and likely contributes to the pro-epileptic role of MCs in early epilepsy. To our surprise, we identified adenosine/A2A receptor (A2AR) as a novel retrograde signaling system that mediates presynaptic LTP at MC-GC synapses. Using the genetically encoded sensor for adenosine GRAB Ado1.0m , we found that neuronal activity triggered phasic, postsynaptic TrkB-dependent release of adenosine. Additionally, seizures released adenosine in vivo, while removing A2ARs from DG decreased seizure susceptibility. Thus, adenosine/A2AR retrograde signaling mediates presynaptic LTP that may contribute to DG-dependent learning and promote epilepsy. |
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| responsibles | Burban |
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Workflow history| from state (1) | to state | comment | date |
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| submitted | published | | 2024/03/13 10:35 UTC |
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