Bidirectional neuro-glial signaling modalities in the hypothalamus: role in neurohumoral regulation

Maintenance of bodily homeostasis requires concerted interactions between the neuroendocrine and the autonomic nervous systems, which generate adaptive neurohumoral outflows in response to a variety of sensory inputs. Moreover, an exacerbated neurohumoral activation is recognized to be a critical component in numerous disease conditions, including hypertension, heart failure, stress, and the metabolic syndrome. Thus, the study of neurohumoral regulation in the brain is of critical physiological and pathological relevance. Most of the work in the field over the last decades has been centered on elucidating neuronal mechanisms and pathways involved in neurohumoral control. More recently however, it has become increasingly clear that non-neuronal cell types, particularly astrocytes and microglial cells, actively participate in information processing in areas of the brain involved in neuroendocrine and autonomic control. Thus, in this work, we review recent advances in our understanding of neuro-glial interactions within the hypothalamic supraoptic and paraventricular nuclei, and their impact on neurohumoral integration in these nuclei. Major topics reviewed include anatomical and functional properties of the neuro-glial microenvironment, neuron-to-astrocyte signaling, gliotransmitters, and astrocyte regulation of signaling molecules in the extracellular space. We aimed in this review to highlight the importance of neuro-glial bidirectional interactions in information processing within major hypothalamic networks involved in neurohumoral integration.