Release of the nitric-oxide (NO) precursor, arginine, from the thalamus in vivo evoked by sensory stimulation and excitatory amino acids. T E Salt, K E Binns, B Benz & K Q Do, Department Of Visual Science, Institute of Ophthalmology, LONDON EC1V 9EL, UK, and Brain Research Institute, Zurich University, Zurich, Switzerland.

The identity of the neurotransmitter(s) which participate in the responses of thalamic relay neurones to sensory stimuli is still unclear, although the responses of ventrobasal (VB) thalamus neurones to natural stimulation of somatosensory afferents of the rat are mediated by ionotropic excitatory amino acid (EAA) receptors when stimulation is performed using an air jet directed at the vibrissa receptive field. Using a similar natural stimulation protocol, together with push-pull perfusion and recording in VB, we have attempted to detect the release of amino acids in the VB thalamus in vivo. We have detected the selective release of arginine among 22 other naturally-occurring amino acids following physiological stimulation of somatosensory afferents. This release of arginine can be blocked by addition of the EAA antagonists CPP (50uM) and CNQX (10uM) to the perfusate, which also block synaptic responses to sensory stimuli. Addition of NMDA (100uM) to the perfusate also evoked release of arginine. These data suggest that release of arginine is dependent upon postsynaptic activation of VB neurones via EAA receptors. Moreover, iontophoretically-applied L-arginine can facilitate sensory synaptic transmission and responses to NMDA and AMPA on VB neurones: this effect was blocked by co-application of L-NAME, an inhibitor of NO synthase. This suggests that the effect of arginine is via the synthesis of the diffusible messenger, NO, and it is possible that the release of arginine is due to an increased requirement for this amino acid for NO synthesis. This may represent a novel, local, positive-feedback, modulatory system which could enhance the responsiveness of thalamic neurones to sensory input.

(This work was supported by the European Science Foundation, grant N 67).