Aim: We investigated whether neurons adjacent to satellite microglia (microglia juxtaposed to neurons with their soma and processes entwining around the neuronal soma) have differences in intrinsic excitability and how this relationship might change after traumatic brain injury (TBI) or with antagonism of the P2Y12 receptor.

Methods: Whole cell patch clamp experiments were performed on in vitro slices of the orbitofrontal cortex (OFC) in sham or TBI conditions or incubation with a P2Y12 receptor antagonist (PSB 0739 1microM) and a series of current steps was used to invoke action potentials. Tmem119 mice (Jackson Laboratory 031823) were utilized to identify GFP+ microglia and determine whether a neuron was adjacent to a satellite microglia or away. TBI was induced with a controlled cortical impact ~1-2 months before testing. Full details are provided in Feichtenbiner et al. (J Neuroinflammation. 2025. 22:9.)

Results: Satellite microglial association reduced the intrinsic excitability of neurons, but this effect was lost after TBI and with antagonism of the P2Y12 receptor.

Main Conclusion: Loss of regulation of neuronal activity by satellite microglia, perhaps through changes in P2Y12 receptors, may be a maladaptive circuit change that occurs and contributes to impairment in chronic TBI.