Fig. 7.

Hypothetical diagram showing the involvement of PPARβ/δ in regulation of glutamate release and photic resetting within the SCN. The light signal triggers glutamate release within the SCN (i.e., acute effects). Glutamate binds to the NMDA receptor, and as a consequence, an influx of calcium occurs. Calcium-mediated activation of the cytoplasmic phospholipase A2 (cPLA2) results in the release of arachidonic acid (AA) from membrane phospholipids for further PPAR β/δ activation and prostaglandin E2 (PGE2) synthesis via cyclooxygenase 2 (COX-2). PGE₂ potentiates light-induced glutamate release. Our pharmacological data indicate that PPARβ/δ activation generates a positive feedback loop on light-induced glutamate release, but blocking PPARβ/δ activation will not impair light-induced phase-shifts (i.e., this is a reinforcing, but not necessary, pathway for photic resetting)