Subcortical neuromodulation of feedforward and feedback inhibitory microcircuits by the reticular activating system

Abstract

GABAergic inhibition originates from distinct subclasses of interneuron subtypes. These interneuron subtypes are highly specialized, exhibiting distinct pre- and postsynaptic properties. The convergence of these specializations enables each interneuron subtype to make a unique but complementary contribution to the function of cortical microcircuits. The existence of morphologically and physiologically distinct interneuron classes raises the possibility of their being controlled independently of one another. Indeed, based on mounting evidence from Somogyi and colleagues for distinct interneuron classes, Nicoll presented a hypothesis that different neuromodulatory systems might exert precise control over principal cell excitability by engaging different interneuron subtypes. Although our knowledge of the manner in which defined interneuron subtypes undergo neuromodulation remains incomplete, there is accumulating evidence that neuromodulatory receptors are differentially expressed on specific GABAergic interneuron subtypes. Therefore, the efficacy of specific GABAergic feedforward and feedback inhibitory circuits will be dynamically regulated by fluctuations in the concentrations of monoamines occurring across the sleep/wake cycle. During periods of wakefulness, alertness, and attention, I propose that the activation of the reticular activating system will engage specific interneuron subtypes in a cell-type specific manner, collectively optimizing sensory processing and information storage in neural microcircuits.