An astrocyte-dependent mechanism for neuronal rhythmogenesis

Rhythmic firing is an essential feature of neuronal circuits generating rhythmic movements. This study shows that this property depends on astrocytes in the trigeminal circuit underlying mastication, where rhythmogenesis relies on activation of a persistent sodium current. Astrocytes modulate this conductance by decreasing the extracellular calcium through release of the calcium-binding protein S100β. Blockade of S100β or inactivation of astrocytes impedes rhythmogenesis. Communication between neurons rests on their capacity to change their firing pattern to encode different messages. For several vital functions, such as respiration and mastication, neurons need to generate a rhythmic firing pattern. Here we show in the rat trigeminal sensori-motor circuit for mastication that this ability depends on regulation of the extracellular Ca 2+ concentration ([Ca 2+ ] e ) by astrocytes. In this circuit, astrocytes respond to sensory stimuli that induce neuronal rhythmic activity, and their blockade with a Ca 2+ chelator prevents neurons from generating a rhythmic bursting pattern. This ability is restored by adding S100β, an astrocytic Ca 2+ -binding protein, to the extracellular space, while application of an anti-S100β antibody prevents generation of rhythmic activity. These results indicate that astrocytes regulate a fundamental neuronal property: the capacity to change firing pattern. These findings may have broad implications for many other neural networks whose functions depend on the generation of rhythmic activity.