Feed‐forward excitation of striatal neuron activity by frontal cortical activation of nitric oxide signaling in vivo

Abstract

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.

NMDA Receptor Gating of Information Flow through the StriatumIn Vivo

“…In this sense, nitric oxide contributes to UP state amplitude in MSNs (West and Grace, 2004). This, together with evidence showing that burst stimulation of the frontal cortex promotes nitric oxide production by striatal interneurons via NMDAR activation (Sammut et al, 2007), suggested that nitric oxide interneurons exert feedforward excitation on MSNs (Ondracek et al, 2008). However, nitric oxide effect relied on an increase in MSN input resistance, which is at odds with our findings.…”

Inhibitory Contribution to Suprathreshold Corticostriatal Responses: An Experimental and Modeling Study

“…Therefore, before their contribution is evaluated, modeling has to be hypothetical. In addition, modulatory influences (e.g., by dopaminergic and cholinergic systems) may change some of these components so that the response may vary dynamically in agreement to brain state (e.g., Suri et al 2001;Tseng et al 2007;Day et al 2008;Ondracek et al 2008;Vautrelle et al 2009). …”

Endocannabinoid–Dopamine Interactions in Striatal Synaptic Plasticity

“…However, NOS inhibitor exposure prevents induction of HFS-induced LTD (Calabresi et al, 1999), making this scenario seem less plausible. It must be noted that some investigators have reported evidence consistent with the idea that NO increases cortical activation of MSN firing (West and Grace, 2004; Ondracek et al, 2008), and of course there is the work implicating NO in LTP in several brain regions including hippocampus (Schuman and Madison, 1991) and even striatum (Doreulee et al, 2003). Thus, it is unclear why this effect would not counteract LTD upon indiscriminate MSN sampling.…”