P2X7 purinergic receptor modulates dentate gyrus excitatory neurotransmission and alleviates schizophrenia-like symptoms in mouse
Lumei Huang,
Paula Mut-Arbona,
Bernadett Varga,
Bibiana Török,
János Brunner,
Antonia Arszovszki,
András Iring,
Máté Kisfali,
E. Sylvester Vizi,
Beáta Sperlágh
Affiliations
Lumei Huang
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary; János Szentágothai Doctoral School, Semmelweis University, 1085 Budapest, Hungary
Paula Mut-Arbona
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary; János Szentágothai Doctoral School, Semmelweis University, 1085 Budapest, Hungary
Bernadett Varga
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary; János Szentágothai Doctoral School, Semmelweis University, 1085 Budapest, Hungary
Bibiana Török
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary
János Brunner
Laboratory of Cellular Neuropharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary
Antonia Arszovszki
Laboratory of Cellular Neuropharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary
András Iring
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary
Máté Kisfali
Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, 1083 Budapest, Hungary
E. Sylvester Vizi
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary; János Szentágothai Doctoral School, Semmelweis University, 1085 Budapest, Hungary
Beáta Sperlágh
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, 1083 Budapest, Hungary; János Szentágothai Doctoral School, Semmelweis University, 1085 Budapest, Hungary; Corresponding author
Summary: ATP-gated P2X7 receptors (P2X7Rs) play a crucial role in brain disorders. However, how they affect normal and pathological synaptic transmission is still largely unclear. Here, by using whole-cell patch-clamp technique to record AMPA- and NMDA receptor-mediated excitatory postsynaptic currents (s/mEPSCs) in dentate gyrus granule cells (DG GCs), we revealed a modulation by P2X7Rs of presynaptic sites, especially originated from entorhinal cortex (EC)-GC path but not the mossy cell (MC)-GC path. The involvement of P2X7Rs was confirmed using a pharmacological approach. Additionally, the acute activation of P2X7Rs directly elevated calcium influx from EC-GC terminals. In postnatal phencyclidine (PCP)-induced mouse model of schizophrenia, we observed that P2X7R deficiency restored the EC-GC synapse alteration and alleviated PCP-induced symptoms. To summarize, P2X7Rs participate in the modulation of GC excitatory neurotransmission in the DG via EC-GC pathway, contributing to pathological alterations of neuronal functions leading to neurodevelopmental disorders.
