Abstract: Nogo-A is known to restrict plasticity in the adult central nervous system, and signalling through its cognate receptors modulates synaptic spine architecture and excitatory glutamate transmission via restricting synaptic glutamate receptor levels and their delivery to the post-synaptic compartments. A recent report now indicates that Nogo-A, signaling through Sphingosine-1-Phosphate Receptor 2, also strengthens inhibitory gamma amino acid butyric acid (GABA)ergic transmission by limiting the diffusion dynamics of GABAA receptors. This reciprocal modulation of excitatory and inhibitory signaling via neurotransmitter receptor dynamics by Nogo-A likely plays important pathophysiological roles in synaptic plasticity during development and injury.