A kinetic model for the frequency dependence of cholinergic modulation at hippocampal GABAergic synapses

Emily Stone, Heikki Haario, J. Josh Lawrence

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Pages (from-to)162-175
Number of pages14
JournalMathematical Biosciences
Volume258
DOIs
StatePublished - Dec 1 2014

Keywords

  • Cholinergic modulation
  • Hippocampal GABAergic synapses
  • Markov Chain Monte Carlo parameter estimation
  • Presynaptic depression

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