The gaseous neurotransmitter nitric oxide plays an important role in the modulation of corticostriatal synaptic transmission. This study examined the impact of frontal cortex stimulation on striatal nitric oxide efflux and neuron activity in urethane-anesthetized rats using amperometric microsensor and single-unit extracellular recordings, respectively. Systemic administration of the neuronal nitric oxide synthase inhibitor 7-nitroindazole decreased spontaneous spike activity without affecting activity evoked by single-pulse stimulation of the ipsilateral cortex. Train (30 Hz) stimulation of the contralateral frontal cortex transiently increased nitric oxide efflux in a robust and reproducible manner. Evoked nitric oxide efflux was attenuated by systemic administration of 7-nitroindazole and the non-selective nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. Train stimulation of the contralateral cortex, in a manner identical to that used to evoke nitric oxide efflux, had variable effects on spike activity assessed during the train stimulation trial, but induced a short-term depression of cortically evoked activity in the first post-train stimulation trial. Interestingly, 7-nitroindazole potently decreased cortically evoked activity recorded during the train stimulation trial. Moreover, the short-term depression of spike activity induced by train stimulation was enhanced following pretreatment with 7-nitroindazole and attenuated after systemic administration of the dopamine D2 receptor antagonist eticlopride. These results demonstrate that robust activation of frontal cortical afferents in the intact animal activates a powerful nitric oxide-mediated feed-forward excitation which partially offsets concurrent D2 receptor-mediated short-term inhibitory influences on striatal neuron activity. Thus, nitric oxide signaling is likely to play an important role in the integration of corticostriatal sensorimotor information in striatal networks.

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Many studies have demonstrated the presence of scale invariance and long-range correlation in animal and human neuronal spike trains. The methodologies to extract the fractal or scale-invariant properties, however, do not address the issue as to the existence within the train of fine temporal structures embedded in the global fractal organisation. The present study addresses this question in human spike trains by the chaos game representation (CGR) approach, a graphical analysis with which specific temporal sequences reveal themselves as geometric structures in the graphical representation. The neuronal spike train data were obtained from patients whilst undergoing pallidotomy. Using this approach, we observed highly structured regions in the representation, indicating the presence of specific preferred sequences of interspike intervals within the train. Furthermore, we observed that for a given spike train, the higher the magnitude of its scaling exponent, the more pronounced the geometric patterns in the representation and, hence, higher probability of occurrence of specific subsequences. Given its ability to detect and specify in detail the preferred sequences of interspike intervals, we believe that CGR is a useful adjunct to the existing set of methodologies for spike train analysis.