SUMMARY OF WORK
Microglia-neuron crosstalk in development is critical for the formation and refinement of synaptic connections. In
this project, I propose to investigate a novel role for the neuron-derived cytokine IL34 in controlling the function
of microglia to close critical periods of synaptic plasticity in development. IL34, along with the canonical ligand
CSF1, signals through the CSF1 receptor on microglia to promote differentiation. Previous work suggests that
embryonic and neonatal microglia depend primarily on CSF1 from other glia, while adult microglia in regions
such as the cortex and striatum depend on IL34 from neurons. I have shown that IL34 expression increases
between postnatal day 8 (P8) and P15 in the anterior cingulate cortex. Interestingly, this window corresponds
with peak synapse engulfment in the ACC, suggesting that IL34 may play a role in dictating microglial function
rather than just survival. Furthermore, my preliminary data demonstrate that microglia in mice lacking functional
IL34LacZ/LacZ show an elevated inflammatory profile and do not upregulate microglial “maturity” marker TMEM119
between P8 and P15. The overarching goal of this proposal is to test the hypothesis that IL34 is a neuronal
activity-dependent signal that influences microglia function to close critical periods of developmental plasticity.
In Aim 1 I will investigate how chemogenetic activation or inhibition of neuronal activity in development controls
IL34 gene and protein expression in all neuron subtypes. In Aim 2, I will determine whether transiently blocking
IL34 or CSF1 impacts microglial pruning of thalamocortical synapses in the ACC, and if this has an effect of
communicative behaviors (USVs). These studies will elucidate the mechanistic implications of differential CSF1R
signaling in the brain during development, and the functional consequences for microglial.