Electrophysiology of neurons adjacent and away from microglia in control and TBI conditions

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.