Heterosynaptic GABAergic plasticity bidirectionally driven by the activity of pre- and postsynaptic NMDA receptors.

Dynamic changes of the strength of inhibitory synapses play a crucial role in processing neural information and in balancing network activity. Here, we report that the efficacy of GABAergic connections between Golgi cells and granule cells in the cerebellum is persistently altered by the activity of glutamatergic synapses. This form of plasticity is heterosynaptic and is expressed as an increase (long-term potentiation, LTPGABA) or a decrease (long-term depression, LTDGABA) of neurotransmitter release. LTPGABA is induced by postsynaptic NMDA receptor activation, leading to calcium increase and retrograde diffusion of nitric oxide, whereas LTDGABA depends on presynaptic NMDA receptor opening. The sign of plasticity is determined by the activation state of target granule and Golgi cells during the induction processes. By controlling the timing of spikes emitted by granule cells, this form of bidirectional plasticity provides a dynamic control of the granular layer encoding capacity.