<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Pati, Sthitapranjya</style></author><author><style face="normal" font="default" size="100%">Salvi, Sonali S.</style></author><author><style face="normal" font="default" size="100%">Kallianpur, Mamata</style></author><author><style face="normal" font="default" size="100%">Vaidya, Bhupesh</style></author><author><style face="normal" font="default" size="100%">Banerjee, Antara</style></author><author><style face="normal" font="default" size="100%">Maiti, Sudipta</style></author><author><style face="normal" font="default" size="100%">Clement, James P.</style></author><author><style face="normal" font="default" size="100%">Vaidya, Vidita A.</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Chemogenetic Activation of Excitatory Neurons Alters Hippocampal Neurotransmission in a Dose-Dependent Manner</style></title><secondary-title><style face="normal" font="default" size="100%">eneuro</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019-11-01 00:00:00</style></date></pub-dates></dates><elocation-id><style  face="normal" font="default" size="100%">ENEURO.0124-19.2019</style></elocation-id><doi><style  face="normal" font="default" size="100%">10.1523/ENEURO.0124-19.2019</style></doi><volume><style face="normal" font="default" size="100%">6</style></volume><issue><style face="normal" font="default" size="100%">6</style></issue><abstract><style  face="normal" font="default" size="100%">Designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tools are extensively used to manipulate neuronal activity in a cell type-specific manner. Whole-cell patch-clamp recordings indicate membrane depolarization, coupled with increased neuronal firing rate, following administration of the DREADD ligand, clozapine-N-oxide (CNO) to activate the Gq-coupled DREADD, hM3Dq. Although hM3Dq has been used to enhance neuronal firing in order to manipulate diverse behaviors, often within 30 min to 1 h after CNO administration, the physiological effects on excitatory neurotransmission remain poorly understood. We investigated the influence of CNO-mediated hM3Dq DREADD activation on distinct aspects of hippocampal excitatory neurotransmission at the Schaffer collateral-CA1 synapse in hippocampal slices derived from mice expressing hM3Dq in Ca2+/calmodulin-dependent protein kinase α (CamKIIα)-positive excitatory neurons. Our results indicate a clear dose-dependent effect on field EPSP (fEPSP) slope, with no change noted at the lower dose of CNO (1 μM) and a significant, long-term decline in fEPSP slope observed at higher doses (5–20 μM). Further, we noted a robust θ burst stimulus (TBS) induced long-term potentiation (LTP) in the presence of the lower CNO (1 μM) dose, which was significantly attenuated at the higher CNO (20 μM) dose. Whole-cell patch-clamp recording revealed both complex dose-dependent regulation of excitability, and spontaneous and evoked activity of CA1 pyramidal neurons in response to hM3Dq activation across CNO concentrations. Our data indicate that CNO-mediated activation of the hM3Dq DREADD results in dose-dependent regulation of excitatory hippocampal neurotransmission and highlight the importance of careful interpretation of behavioral experiments involving chemogenetic manipulation.</style></abstract></record></records></xml>