Adenosine A2A receptor modulates microglia-mediated synaptic pruning of the retinogeniculate pathway during postnatal development

The adenosine A2A receptor antagonist KW6002 distinctly regulates retinal ganglion cell morphology during postnatal development and neonatal inflammation

“…The littermates of the Thy1-YFPH mice were randomly divided into two groups. Pups received intraperitoneal (IP) injections of the A 2A R antagonist KW6002 (10 mg/kg body weight, freshly prepared in dimethyl sulfoxide (DMSO, Sigma), ethoxylated castor oil (Sigma), and phosphatebuffered saline (PBS) with a proportion of 15%:15%:70% (Miao et al, 2021)) every day from P4 to P6. The control group was administered the corresponding vehicle in the same volume.…”

“…Both in vitro and in vivo studies have revealed that A 2A Rs play important roles in brain development (Silva et al, 2013;Ribeiro et al, 2016;Alcada-Morais et al, 2021). Our previous study has found that A 2A Rs modulate microglia-mediated synaptic pruning of the retinogeniculate pathway in the dorsal lateral geniculate during postnatal development (Miao et al, 2021). However, the exact role of the A 2A Rs on the development of retinal neurons including different RGC types is still not known.…”

Microglia: Activity‐dependent regulators of neural circuits

“…A later study showed that either pharmacologically blocking or genetically ablating adenosine A 2A receptors (A 2A R), which are known to drive retinal waves of spontaneous activity and retinogeniculate synaptic pruning, 34 can also result in decreased microglial engulfment and elimination of retinogeniculate synapses. 35 Despite this evidence for an activity-dependent mechanism, how activity influences microglial engulfment of synapses remained an open question.…”

“…Supporting an activity‐dependent mechanism, when RGCs from one eye were silenced with tetrodotoxin, microglia preferentially engulfed presynaptic material within the LGN from those inactive neurons; 30 conversely, enhancing activity in a subset of neurons with a cyclic adenosine monophosphate analog decreased microglial engulfment of more active presynaptic inputs in the LGN. A later study showed that either pharmacologically blocking or genetically ablating adenosine A 2A receptors (A 2A R), which are known to drive retinal waves of spontaneous activity and retinogeniculate synaptic pruning, 34 can also result in decreased microglial engulfment and elimination of retinogeniculate synapses 35 . Despite this evidence for an activity‐dependent mechanism, how activity influences microglial engulfment of synapses remained an open question.…”