title: A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses.
abstract: In this paper we use a simple model of presynaptic neuromodulation of GABA signaling to decipher paired whole-cell recordings of frequency dependent cholinergic neuromodulation at CA1 parvalbumin-containing basket cell (PV BC)-pyramidal cell synapses. Variance-mean analysis is employed to normalize the data, which is then used to estimate parameters in the mathematical model. Various parameterizations and hidden parameter dependencies are investigated using Markov Chain Monte Carlo (MCMC) parameter estimation techniques. This analysis reveals that frequency dependence of cholinergic modulation requires both calcium-dependent recovery from depression and mAChR-induced inhibition of presynaptic calcium entry. A reduction in calcium entry into the presynaptic terminal in the kinetic model accounted for the frequency-dependent effects of mAChR activation.
authors.affiliation: Department of Mathematical Sciences, The University of Montana Missoula, MT 59812, USA. Electronic address: stone@mso.umt.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Stone
authors.affiliation: Department of Mathematics and Physics, Lappeenranta University of Technology, Lappeenranta, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Haario
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, The University of Montana Missoula, MT 59812, USA.
authors.forename: J Josh
authors.initials: JJ
authors.lastname: Lawrence
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008962:Models, Theoretical; D017966:Pyramidal Cells / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine
keywords: Cholinergic modulation; Hippocampal GABAergic synapses; Markov Chain Monte Carlo parameter estimation; Presynaptic depression