ROLE OF THE P2Y1 RECEPTOR IN NEUROMODULATION OF OLFACTORY SIGNALS PROCESSING

Adenosine 5'-triphosphate (ATP) plays an important role as a co-transmitter in the nervous system. ATP activates purinergic signaling by binding to P2 receptors. Here, we want to investigate the role of purinergic neuromodulation for the processing of olfactory signals. Olfactory receptor neurons (ORNs) detect odors and project to the olfactory bulb. There, within separate processing units called glomeruli, the ORN axons release glutamate and ATP exciting mitral cells (MCs) which integrate excitatory input from ORNs and serve as the output neurons of the olfactory bulb. Using patch-clamp recording of MCs in acute brain slices revealed that the uncaging of caged ATP in the glomerulus significantly depolarizes MCs, with the selective P2Y1 antagonist MRS2179 reducing strongly the uncaging response. Therefore MCs in the olfactory bulb are modulated by ATP through a P2Y1 receptor-dependent pathway. Furthermore, approximately 50% of ATP-induced excitation was mediated by glutamate, since the ATP- effect was reduced in the presence of glutamate receptor blockers. Application of TTX suppressed the glutamatergic feed-forward mechanism whereas a small mitral cell depolarization persisted. Moreover, mitral and tufted cell specific p2y1ko mice was shown no reduction in the effect of MRS2179 and ATP-response.Importantly, the astrocytic network, examined by confocal Ca2+ imaging in parallel with mitral cell recording in astrocyte-specific P2Y1 knockout mice, was found not to reduce the effects of MRS2179 on mitral cell ATP-response. In conclusion, this pathway highlights a modulatory role of ATP in olfactory processing, involving both purinergic receptor-mediated excitation and an indirect glutamatergic feed-forward mechanism in MCs.