NEW TARGETS OF GLYCINE SIGNALING IN THE MOUSE FOREBRAIN
01/29/2020
Imre Kalló1, Balázs Pál2, Krisztina Nagy1, Tsogbadrakh Bayasgalan2, Csemer Andrea2, Mohanraj Mahendravarman1, Masahiko Watanabe3, László Záborszky4 and Zsuzsanna Bardóczi1, 5
1 Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Budapest
2 Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen
3 Department of Anatomy, Hokkaido University School of Medicine, Sapporo
4 Center for Molecular and Behavioral Neuroscience, Rutgers, Newark
5 Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Budapest
Cholinergic neurons receive a rich glycinergic input in the basal forebrain (BF). We have demonstrated glycine’s effect on BF cholinergic (BFC) neurons by detecting bicuculline-resistant, strychnine-sensitive sIPSCs. To investigate, whether glycine influences also the excitatory input of BFC neurons, whole cell recordings were carried out in the presence of an antagonist of the glycine-binding site of the NMDA receptor (DCKA), which revealed a significant reduction of the frequency of EPSCs. BFC neurons are admixed in the same region with other cell types. Immunohistochemical double labelling revealed glycine receptor-immunoreactive (IR) sites at choline acetyltransferase-immunonegative cells, indicating that they could also be under direct influence of glycinergic neurons. Therefore, we have also examined the non-cholinergic BF neurons for receiving glycinergic afferents. Immunohistochemical double labeling was carried out to reveal, whether glycine transporter-2 (GLYT2)-IR axons establish connection with BF parvalbumin (PV), calbindin (CB), calretinin (CR) and/or somatostatin (SS)-IR neurons. Light- and confocal microscopic analysis of the samples revealed GLYT2-IR axon varicosities in apposition to PV-, CB-, and CR-IR neurons in the nucleus of the horizontal limb of the diagonal band. No such close relationship could be observed for SS-IR neurons. Correlated electron microscopy confirmed the presence of synaptic contacts between GLYT2- and PV-, CB-, or CR-IR neurons.These data extend the target cells population of the ascending glycinergic input and mechanisms of action in the BF and concurrently initiate efforts to distinguish further subgroups (concerning afferent- and or efferent connections, co-expressed neurotransmitters and/or receptors) to clarify the functional role of their glycinergic input. Supported by OTKA K-18_129142 to IK and BP, NIH/NINDS Grant NSO23945 to LZ