Aim: 

In a previous study we evidenced that increased local levels of nitric oxide (NO) exert excitatory effects on subthalamic neurons. This study aims to investigate the possible involvement of a modulatory influence of NO on the GABA-evoked responses of neurons in the subthalamic nucleus.

Methods: 

Extracellular single neuron activity from urethane anesthetized rats was recorded. GABA, S-Nitroso-Glutathione (SNOG, NO donor) and Nw-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor) were administered through microiontophoresis. The ability of NO to alter the magnitude of GABA-evoked responses and the ratio between GABA-evoked activity (''signal'') and spontaneous firing (''noise'') was used as an indicator of nitrergic modulation.

Results: 

The majority of subthalamic cells were sensitive to iontophoretically applied SNOG or L-NAME, showing excitatory or inhibitory responses, respectively. Nearly all neurons responding to SNOG (52/69) or L-NAME (34/49) showed responses to iontophoretic GABA administration, all displaying a decreased firing rate when GABA was applied. When a NO-active drug was co-iontophoresed with GABA, significant changes of both the magnitude and signal-to-noise ratio of GABA responses were generally observed: under SNOG continuous ejection, the signal-to-noise ratio of GABA-evoked responses was reduced, while it was enhanced during L-NAME continuous administration.

Conclusion: 

Our present data suggest the existence of a strong modulation of the activity of subthalamic neurons exerted by NO neurotransmission, which could partly be due to an interaction between NO and GABA neurotransmitter systems, probably through the modulation of GABA_A receptor activity.