Asymmetric spike-timing dependent plasticity of striatal nitric oxide-synthase interneurons

Abstract

Corticostriatal projections constitute the major inputs to basal ganglia, an ensemble of sub-cortical nuclei involved in the learning of cognitive-motor sequences in response to environmental stimuli. Besides striatal output neurons (medium-sized spiny neurons, MSNs) in charge of the detection of cortical activity, three main classes of interneurons (GABAergic, cholinergic and nitric oxide (NO)-synthase interneurons) tightly regulate the corticostriatal information transfer. Despite the crucial role of NO on neuronal signaling and synaptic plasticity, little is known about corticostriatal synaptic transmission and plasticity at the level of striatal neuronal nitric oxide synthase (nNOS) interneurons. Using a corticostriatal rat brain slice preserving the connections between the somatosensory cortex and the striatal cells, we have explored the synaptic transmission between the cerebral cortex and striatal nNOS interneurons and their capability to develop activity-dependent long-term plasticity based on the quasi-coincident cortical and striatal activities (spike-timing dependent plasticity, STDP). We have observed that cortical pyramidal cells activate monosynaptically and very efficiently the striatal nNOS interneurons. In addition, nNOS interneurons are able to develop strong bidirectional long-term plasticity, following STDP protocols. Indeed, the strength of cortically-evoked response at nNOS interneurons varied as a function of time interval between pre- and postsynaptic activations (Deltat=t(post)-t(pre)). For Deltat<0, excitatory post-synaptic currents (EPSCs) were depressed, peaking at a delay of -25 ms. For Deltat>0, EPSCs depressed for 0<Deltat<+30 ms (peaking at +23 ms) and potentiated for +30<Deltat<+65 ms (peaking at +42 ms). The present study reports a direct connection between the striatal nNOS interneurons and the cerebral cortex, and the existence of long-term synaptic plasticity. In addition, this constitutes the first report of an asymmetric bidirectional STDP, with long-term depression (LTD) induced for Deltat<0 and "early" Deltat>0 and long-term potentiation (LTP) induced by "late" Deltat>0.