Nitric-Oxide Producing Cells in the Somatosensory Cortex: Distinct Roles for Astrocytes and GABAergic neurons

Nitric oxide (NO) has been recognized as an atypical neuronal messenger affecting synaptic transmission, but its cellular source has remained unresolved as the neuronal NO synthase isoform (nNOS) in brain areas such as the neocortex is expressed only by a small subset of inhibitory neurons. The involvement of the glial NOS isoform (iNOS) in modulating neuronal activity has been largely ignored since it has been accepted that this enzyme is regulated by gene induction following detrimental stimuli. Using NO imaging in acute neocortical slices and electrophysiology, we discovered that both neurons and astrocytes were capable of producing NO on a fast time scale.

Using the NO-indicator to induce phototoxic damage to NO-producing inhibitory neurons, we found that these neurons communicate significant lateral inhibition that shapes the horizontal spread of the activity in the neocortex. Astrocytes seemed resistant to this phototoxic damage. In another set of experiments, we demonstrate that selective inhibition of iNOS reduced both spontaneous and evoked synaptic release. Moreover, iNOS inhibition partially prevented and reversed the potentiation of excitatory synapses in layer 2/3 pyramidal neurons.These data point to astrocytes as a source for the nitrosative regulation of synaptic release in the neocortex.