The sensory thalamus serves as a hub for incoming information encoding different features of the
outside world. This information is parsed and modified as it is transmitted to the cortex. In the visual
thalamus (the dorsal lateral geniculate nucleus), retinal ganglion cell axons converge onto proximal
dendrites of thalamocortical neurons, forming clusters of boutons that stud the dendrites. Many of
these bouton clusters are ensheathed by astrocytes along with synaptic terminals from
neuromodulatory projections and inhibitory dendrodendritic presynaptic terminals. Collectively, this
synaptic motif is called the glomerulus, described beautifully by electron microscopy in many thalamic
nuclei and across many species. While the glomerulus is quite striking, the functional relevance of
this structural motif is still debated.
To address this critical question, here, we propose to establish and characterize mice in which the
glomerular astrocytic sheath is disrupted by genetic deletion of a member of the family of fibroblast
growth factor receptors. Our preliminary data shows that deletion of this receptor from astrocytes
results in reduced astrocytic sheaths around clusters of retinal ganglion cell boutons and aberrant
retinogeniculate functional refinement. We will extend these findings to elucidate the role of this
receptor in the development of astrocytic morphology, glomerular structure and the elimination and
strengthening of retinogeniculate synapses in the visual thalamus. We will also examine whether and
how defects in astrocytic ensheathment of the glomerulus may contribute to aberrant retinogeniculate
synapse refinement. Finally, we will take advantage of the disrupted glomerular ensheathment in
mutant mice to test the hypothesis that the glomerular structure enhances crosstalk between
synapses within the astrocytic sheath that is mediated by glutamate and GABA spillover.
If these proposed experiments are successful, results from these studies will advance our
understanding of how information is organized in the thalamus and the functional sequela of
disruption of this organization.