– Assessing the mechanism and the functional impact of activity-dependent synaptic plasticity –

Kaoutsar Nasrallah

Albert Einstein College of Medecine
New York

Abstract
Activity-dependent synaptic plasticity, a process by which synapses can strengthen or weaken in response to neuronal activity, is believed to be a core mechanism involved in memory formation while alterations in synaptic function are associated with brain diseases. The dentate gyrus (DG), a major input area of the hippocampus, contains two types of excitatory neurons: dentate granule cells (GCs) and hilar mossy cells (MCs). MCs and GCs form an important but under-investigated associative circuit, that is implicated in DG-dependent cognitive functions and epilepsy. Yet, very little was known about the dynamic properties of GC-MC-GC associative circuit, which we aimed to address. Remarkably, a single MC contacts about 30,000 GCs. We recently found that MC-GC synapses express a robust form of presynaptic long-term potentiation (MC-GC LTP) that increases DG output. Importantly, initial epileptic seizures trigger broad MC-GC LTP in vivo, which promotes further seizures. It is therefore crucial to understand the molecular processes underlying MC-GC synaptic strengthening. MC-GC LTP requires both postsynaptic TrkB activation and presynaptic cAMP/PKA signaling, indicating the involvement of a retrograde messenger, whose identity was unknown. To our surprise, we found that most conventional retrograde messengers were not implicated in this form of plasticity. Instead, MC-GC LTP is mediated by the novel adenosine/A2AR retrograde signaling system by which BDNF/TrkB and A2ARs may contribute to DG-dependent form of learning and epilepsy. Building up on my previous research experiences, my independent research program will investigate the role of δ-containing GABAA receptors in hippocampal function (e.g. memory) and disease (e.g. epilepsy).

Funding: National Institute of Health (NIH), R01-NS113600 and R01-MH125772 grants to PEC.
Fondation pour la Recherche Médicale (Postdoctoral Fellowship for a research abroad), the
Fondation Bettencourt Schueller (Prix pour les Jeunes Chercheurs 2016) and the American
Epilepsy Society Postdoctoral Research Fellowship (2020) to KN.
No conflict of interest to declare.

Invited by Rosa Cossart

Zoom Metting – January 24th at 2p.m

https://zoom.us/j/96798160455?pwd=TTIwT3BWZFUveWRJeGlpMU1idzBudz09

ID de réunion : 967 9816 0455
Code secret : KH2Y8f