Unravelling neuron-astrocyte communication in the dorsal raphe nucleus.

Abstract

Introduction: Serotonin is a neuromodulator widely spread throughout the central nervous system and involved in a vast variety of behaviors, such as cognitive functions and emotional states. On this basis, serotonergic dysfunction has been related to several psychiatric disorders such as Major Depressive Disorder, schizophrenia, or autism. Despite serotonin’s widespread distribution, the location of serotonergic neurons is restricted to the midbrain raphe nuclei. In this context, astrocytes are known to participate in synaptic transmission modulating neural circuits; however, their role in the serotonergic system remains largely unknown. My study aims to elucidate the neuron-astrocyte signaling at serotonergic nuclei, looking at the dorsal raphe nucleus (DRN). Materials and methods: For the purpose of this project, we performed intracranial injections of viral constructs in adult mice to express the Ca2+ indicator GCaMP6 specifically in DRN astrocytes, Ca2+ imaging experiments to record astrocytic activity, electrophysiological recordings of neuronal activity using patch-clamp and immunohistochemistry techniques. Results and conclusions: Preliminary data show that astrocytes from DRN respond to serotonin with an increase in the amplitude and frequency of intracellular Ca2+ events, which is partly mediated by serotonin type 2 receptors. As a consequence of triggering Ca2+ signaling, we found that serotonin induces gliotransmission, shown by an increased frequency of Slow Inward Currents (SICs) and modulation of excitatory synaptic transmission in dorsal raphe neurons. In conclusion, these data suggest that astrocytes might play a role in synaptic transmission and neuronal excitability in the DRN and, therefore, in the serotonergic-mediated actions of DRN.