
@article {96750,
	title = {Reciprocal regulation of spontaneous synaptic vesicle fusion by Fragile X mental retardation protein and group I metabotropic glutamate receptors.},
	journal = {J Neurochem},
	year = {2021},
	month = {2021 Jul 29},
	abstract = {<p>Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a range of aberrations in synaptic signaling pathways and plasticity associated with group I metabotropic glutamate (mGlu) receptors. These studies, however, have mostly focused on the postsynaptic functions of FMRP and mGlu receptor activation, and relatively little is known about their presynaptic effects. Neurotransmitter release is mediated via multiple forms of synaptic vesicle (SV) fusion, each of which contribute to specific neuronal functions. The impacts of mGlu receptor activation and loss of FMRP on these SV fusion events remains unexplored. Here we combined electrophysiological and fluorescence imaging analyses on primary hippocampal cultures prepared from a Fmr1 knockout (KO) rat model. Compared to wild-type (WT) hippocampal neurons, KO neurons displayed an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), as well as spontaneous SV fusion events. Pharmacological activation of mGlu receptors in WT neurons caused a similar increase in spontaneous SV fusion and sEPSC frequency. Notably, this increase in SV fusion was not observed when spontaneous activity was blocked using the sodium channel antagonist tetrodotoxin. Importantly, the effect of mGlu receptor activation on spontaneous SV fusion was occluded in Fmr1 KO neurons. Together, our results reveal that FMRP represses spontaneous presynaptic SV fusion, whereas mGlu receptor activation increases this event. This reciprocal control appears to be mediated via their regulation of intrinsic neuronal excitability.</p>
},
	issn = {1471-4159},
	doi = {10.1111/jnc.15484},
	author = {Subrahmanyam, Rohini and Dwivedi, Deepanjali and Rashid, Zubin and Bonnycastle, Katherine and Cousin, Michael A and Chattarji, Sumantra}
}
