Delivery of graphene oxide nanosheets modulates glutamate release and normalizes amygdala synaptic plasticity to improve anxiety-related behavior

Graphene oxide nanosheets (GO) were reported to alter neurobio- logical processes involving cell membrane dynamics. GO ability to reversibly downregulate specifically glutamatergic synapses under- pins their potential in future neurotherapeutic developments. Aberrant glutamate plasticity contributes to stress-related psycho- pathology and drugs which target dysregulated glutamate rep- resent promising treatments. We find that in a rat model of post- traumatic stress disorder (PTSD), a single injection of GO to the lateral amygdala following the stressful event induced PTSD- related behavior remission and reduced dendritic spine densities. We explored from a mechanistic perspective how GO could impair glutamate synaptic plasticity. By simultaneous patch clamp pair recordings of unitary synaptic currents, live-imaging of presynaptic vesicle release and confocal microscopy, we report that GO nanosheets altered the probability of release enhancing the extinc- tion of synaptic plasticity in the amygdala. These findings show that the modulation of presynaptic glutamate release might rep- resent an unexplored target for (nano)pharmacological interven- tions of stress-related disorders.