Frontal cortical afferents facilitate striatal nitric oxide transmission in vivo via a NMDA receptor and neuronal NOS-dependent mechanism.
Striatal nitric oxide (NO) signaling plays a critical role in modulating neural processing and motor behavior. Nitrergic interneurons receive synaptic inputs from corticostriatal neurons and are activated via ionotropic glutamate receptor stimulation. However, the afferent regulation of NO signaling is poorly characterized. The role of frontal cortical afferents in regulating NO transmission was assessed in anesthetized rats using amperometric microsensor measurements of NO efflux and local field potential recordings. Low frequency (3 Hz) electrical stimulation of the ipsilateral cortex did not consistently evoke detectable changes in striatal NO efflux. In contrast, train stimulation (30 Hz) of frontal cortical afferents facilitated NO efflux in a stimulus intensity-dependent manner. Nitric oxide efflux evoked by train stimulation was transient, reproducible over time, and attenuated by systemic administration of either the NMDA receptor antagonist MK-801 or the neuronal NO synthase inhibitors 7-nitroindazole and NG-propyl-L-arginine. The interaction between NO efflux evoked via train stimulation and local striatal neuron activity was assessed using dual microsensor and local field potential recordings carried out concurrently in the contralateral and ipsilateral striatum, respectively. Systemic administration of the non-specific NO synthase inhibitor methylene blue attenuated both evoked NO efflux and the peak oscillation frequency (within the delta band) of local field potentials recorded immediately after train stimulation. Taken together, these observations indicate that feed-forward activation of neuronal NO signaling by phasic activation of frontal cortical afferents facilitates the synchronization of glutamate driven oscillations in striatal neurons. Thus, NO signaling may act to amplify coherent corticostriatal transmission and synchronize striatal output.
Sammut
Stephen
S
Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
Park
Diana J
DJ
West
Anthony R
AR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I