Astrocytes restore connectivity and synchronization in dysfunctional cerebellar networks.

Abstract

Evidence suggests that astrocytes play key roles in structural and functional organization of neuronal circuits. To understand how astrocytes influence the physiopathology of cerebellar circuits, we cultured cells from cerebella of mice that lack the <i>ATM</i> gene. Mutations in <i>ATM</i> are causative of the human cerebellar degenerative disease ataxia-telangiectasia. Cerebellar cultures grown from <i>Atm</i>^<i>-/-</i> mice had disrupted network synchronization, atrophied astrocytic arborizations, reduced autophagy levels, and higher numbers of synapses per neuron than wild-type cultures. Chimeric circuitries composed of wild-type astrocytes and <i>Atm</i>^<i>-/-</i> neurons were indistinguishable from wild-type cultures. Adult cerebellar characterizations confirmed disrupted astrocyte morphology, increased GABAergic synaptic markers, and reduced autophagy in <i>Atm</i>^<i>-/-</i> compared with wild-type mice. These results indicate that astrocytes can impact neuronal circuits at levels ranging from synaptic expression to global dynamics.