CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCEDo canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?Dasari, Sameeraa; Abramowitz, Joelb; Birnbaumer, Lutzb; Gulledge, Allan T.a Author Information aDepartment of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, New Hampshire bLaboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Correspondence to Allan T. Gulledge, PhD, Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH 03756-0001, USA Tel: +1 603 650 7731; fax: +1 603 650 6130; e-mail: [email protected] Received March 13, 2013 Accepted April 9, 2013 NeuroReport: July 10, 2013 - Volume 24 - Issue 10 - p 550-554 doi: 10.1097/WNR.0b013e3283621344 Buy Metrics Abstract Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a nonselective cation conductance that produces calcium-dependent ‘afterdepolarizing potentials’ (ADPs) following short trains of action potentials. Although the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient receptor potential (TRPC) channels, specifically the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate, flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC and that the focus of future work should be expanded to test the involvement of other potential ionic effectors. © 2013 Lippincott Williams & Wilkins, Inc.