Excitatory and anti‐oscillatory actions of nitric oxide in thalamus

Abstract

The dorsal lateral geniculate nucleus (dLGN) not only serves as the obligatory pathway for visual information transfer from the retina to neocortex but can also generate intrathalamic rhythmic activities associated with different arousal states and certain pathological conditions. The gating activity of thalamocortical circuits is under neuromodulatory control by various brainstem nuclei as well as intrinsic thalamic neurons (e.g. thalamic reticular nucleus (TRN) neurons and dLGN interneurons). In this study, we examined the effect of the putative neuromodulator nitric oxide (NO) on thalamic neuron excitability. There are multiple potential sources of NO in thalamus: cholinergic terminals originating from brainstem nuclei, GABAergic TRN neurons, and local GABAergic interneurons. Using whole cell recording techniques in in vitro thalamic slices, we found that the NO donor SNAP produced a robust, long-lasting depolarization in TRN neurons, a weaker depolarization in thalamocortical relay neurons, and no effect in local interneurons. SNAP preferentially depolarized stereotypical TRN neurons that could produced strong burst discharge. In contrast, SNAP had little effect on atypical burst and non-burst TRN cells. The NO donor SIN-1 and the endogenous NO precursor, L-arginine, mimicked the SNAP-mediated actions. The NO-mediated depolarizations were blocked by the guanylyl cyclase inhibitor ODQ indicating involvement of the cGMP pathway. In addition, the phosphodiesterase (PDE) inhibitor zaprinast depolarized and occluded the NO-mediated depolarization in TRN neurons. At the circuit level, NO activation significantly attenuated intrathalamic rhythmic activities likely resulting from the shifting of the firing mode of thalamic neurons, perhaps both TRN and thalamocortical neurons, from burst- to tonic-discharge mode. These alterations in thalamic neuron excitability not only change rhythmic circuit activity, but could also influence sensory information processing through thalamocortical circuits.