Early postsynaptic potentiation in hippocampal somatostatin interneurons is mTORC1-dependent and disrupted in Fmr1^-/y...

The synaptic plasticity in hippocampal pyramidal neurons is expressed without a need for activation of gene transcription and protein synthesis during the first hour of induction. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) regulates gene expression at the mRNA translation level and is required for the development of several forms of long-lasting hippocampal synaptic plasticity. However, it is unknown whether this temporal pattern is also present in other cell types, such as interneurons. We stimulated the Oriens-Alveus border to induce synaptic potentiation (SP) in somatostatin-expressing interneurons (SOM-INs). Pre-incubating slices with rapamycin prevented the development of SP during 40 min post-stimulation. To determine the specific role of mTORC1 in SOM-INs, we used a conditional SOM-Raptor^-/- (cKO) mouse line and found that early SP did not develop in SOM-Raptor cKO mice. Moreover, we used Fmr1^-/y mice, an animal model of Fragile X syndrome in which dysregulation of mTOR-dependent signaling pathway is a hallmark of its pathophysiology. Interestingly, SP did not develop in SOM-INs of Fmr1^-/y mice either. We also found a reduction of excitatory synaptic currents in these interneurons in Fmr1^-/y mice, while their membrane intrinsic excitability is comparable to that of wild-type mice. Taken together, we found that the earliest minutes of developing synaptic plasticity in SOM-INs are mTORC1-dependent. Furthermore, we found that this synaptic plasticity is lost in SOM-INs in Fmr1^-/y mice. In sum, the definition of early-phase synaptic plasticity based on its dependency on mTORC1 and its impact on autism pathophysiology should be considered in a synapse-type-specific manner.