Summary
GABA is the principal inhibitory neurotransmitter in the CNS and sustains a variety of brain functions. Dysfunctional GABA signaling is associated with many neurological diseases, including epilepsy, autism, anxiety and schizophrenia. Given its fundamental role in physiology and pathobiology, it is surprising that molecular mechanisms involved in the regulation of the vesicular pools of GABA and their impact on synaptic plasticity and pathophysiology remain elusive. We will present data from a multidiciplinary investigation on Slc38a1/ SAT1/SNAT1 revealing its involvement in multiple functions. Our study shows that the glutamine transporter Slc38a1 sustains GABA neurotransmitter replenishment. It has impact on synaptic vesicle morphology and vesicular neurotransmitter content. Glutamine transport by Slc38a1 also triggers action potentials. Finally, Slc38a1 regulates inhibitory synaptic plasticity and is required for entering the critical periods in the visual cortex. Taken together, our work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.