The Role of Astrocytes in the Development of the Avian Auditory Brainstem

The avian auditory brainstem circuit is a well-characterized model for sensory processing.  The molecular and cellular mechanisms that establish this pathway are just beginning to be understood.  We previously reported that astrocytes that express glial fibrillary acidic protein (GFAP) emerge during a period of extensive reorganization and maturation.  Here we present results on the role of GFAP-positive astrocytes during the maturation of dendrites and the formation of inhibitory synapses in chick auditory brainstem.  Nucleus laminaris (NL), a brainstem nucleus that facilitates sound source localization, exhibits a pronounced gradient of dendritic morphology that optimizes phase-locking.  Astrocytes mature at a time that coincides with the formation of this gradient.  We cultured mature astrocytes, collected astrocyte-conditioned media (ACM), and incubated NL neurons in relatively immature organotypic brainstem slices with this ACM.  Using time-lapse multi-photon imaging we found that ACM promotes the formation of the spatial gradient in NL by systemically eliminating primary dendrites as a function of the neuron’s location along the tonotopic axis.  This period of astrocyte development also coincides with the maturation of inhibitory synapses onto NL neurons.  Using the same organotypic slice preparation and an antibody against the vesicular GABA transporter (VGAT) to identify inhibitory synapses, we found that treatment with ACM results in a significant increase in the number of presynaptic inhibitory sites on NL dendrites.  Together, these results suggest that GFAP-positive astrocytes have specific roles that promote maturation of the auditory brainstem.  Future experiments will seek to identify the signaling mechanisms that mediate these changes.