Effects of new nitric oxide synthase inhibitors on spontaneous locomotor activity

Introduction. New nitric oxide synthase (NOS) inhibitors: 3-bromo-7-nitro- indazole (3-Br-7-NI), 1-(2-trifluoromethylphenyl) imidazole (TRIM), S-methyl-L-thiocitrulline (S-Me-TC) and 7-nitroindazole (7-NI) reduce spontaneous locomotor activity in mice. Material and methods. In order to elucidate central effects of NOS inhibitors on locomotor activity, the influence of 7-NI on electroencephalographic (EEG) power spectrum in rats was investigated. Results. 7-NI reduced the EEG power density in all frequency bands in rats, suggesting a depression of the central neuronal activity. The electrophysiologic power was most reduced in the range of 7-9 Hz of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotor activity observed following administration of NOS inhibitors. Conclusion. The present results indicate that nitric oxide exerts an excitatory effect on central neuronal structures involved in regulation of locomotion. .

Rhythmically Discharging Basal Forebrain Units Comprise Cholinergic, GABAergic, and Putative Glutamatergic Cells

The basal forebrain plays important roles in arousal, learning, and memory by stimulating cortical activation characterized by rhythmic slow theta and high-frequency beta-gamma activities. Although cholinergic neurons play a significant part in these roles, other, including GABAergic, neurons appear to contribute. Using juxtacellular labeling with neurobiotin of neurons recorded within the magnocellular preoptic-substantia innominata area in urethan-anesthetized rats, we show that in addition to cells that are cholinergic or GABAergic, other cells that are neither fire rhythmically in correlation with stimulation-induced rhythmic slow activity on the cortex. Neurons with the characteristics of the noncholinergic/nonGABAergic cells contain phosphate-activated glutaminase (PAG), the synthetic enzyme for transmitter glutamate and may thus be glutamatergic. Within their oscillatory spike trains, putative glutamatergic neurons fire at a lower frequency (∼20 Hz) than the GABAergic neurons (∼40 Hz) and the cholinergic neurons (average: 75 Hz), whose spike trains include high-frequency bursts. The three groups all discharge rhythmically at a slow frequency in correlation with rhythmic slow activity recorded on the prefrontal, entorhinal, piriform and olfactory bulb cortices. The predominant slow frequency corresponds to the respiratory-olfactory rhythm, which is commonly slower than, yet can be as fast as, the hippocampal theta rhythm during certain coordinated behaviors, such as sniffing-whisking. While stimulating higher frequency beta-gamma activities, putative glutamatergic together with GABAergic and cholinergic cells may thus collectively modulate rhythmic slow activity and thereby promote coherent processing and plasticity across distributed cortical networks during coordinated behaviors and states.