Therapeutic needs to modulate brain circuits highlight graphene based materials (GBMs) as emerging tool to engineer specific interventions to treat neuro-diseases. In this context, graphene oxide (GO) nanosheets offer new drug delivery strategies to reach neural cells and signaling networks selectively. To complex and transport neuropeptide Y (NPY), GO was engineered as GO:NPY, and its activity was investigated in regulating excitatory neurotransmission in NPY-positive synaptic pathways, when delivered to the amygdala, a structure mediating fear memory responses. First, it was shown that in vitro GO:NPY specifically and selectively inhibited glutamate release and suppressed synaptic enhancement via NPY receptors. In a rat model of anxiety disorder, when injected into the amygdala, GO:NPY suppressed contextual fear memory responses via activation of NPY receptors in specific synaptic pathways. This easy-to-tune GBM based nanoplatforms promise advances in co-delivery vectors preserving the synaptic specificity needed for treating specific pathological conditions.