Postsynaptic cell type-dependent cholinergic regulation of GABAergic synaptic transmission in rat insular cortex

J Neurophysiol. 2010 Oct;104(4):1933-45. doi: 10.1152/jn.00438.2010. Epub 2010 Aug 4.


The cerebral cortex consists of multiple neuron subtypes whose electrophysiological properties exhibit diverse modulation patterns in response to neurotransmitters, including noradrenaline and acetylcholine (ACh). We performed multiple whole cell patch-clamp recording from layer V GABAergic interneurons and pyramidal cells of rat insular cortex (IC) to examine whether cholinergic effects on unitary inhibitory postsynaptic currents (uIPSCs) are differentially regulated by ACh receptors, depending on their presynaptic and postsynaptic cell subtypes. In fast-spiking (FS) to pyramidal cell synapses, carbachol (10 μM) invariably decreased uIPSC amplitude by 51.0%, accompanied by increases in paired-pulse ratio (PPR) of the second to first uIPSC amplitude, coefficient of variation (CV) of the first uIPSC amplitude, and failure rate. Carbachol-induced uIPSC suppression was dose dependent and blocked by atropine, a muscarinic ACh receptor antagonist. Similar cholinergic suppression was observed in non-FS to pyramidal cell synapses. In contrast, FS to FS/non-FS cell synapses showed heterogeneous effects on uIPSC amplitude by carbachol. In roughly 40% of pairs, carbachol suppressed uIPSCs by 35.8%, whereas in a similar percentage of pairs uIPSCs were increased by 34.8%. Non-FS to FS/non-FS cell synapses also showed carbachol-induced uIPSC facilitation by 29.2% in about half of the pairs, whereas nearly 40% of pairs showed carbachol-induced suppression of uIPSCs by 40.3%. Carbachol tended to increase uIPSC amplitude in interneuron-to-interneuron synapses with higher PPR, suggesting that carbachol facilitates GABA release in interneuron synapses with lower release probability. These results suggest that carbachol-induced effects on uIPSCs are not homogeneous but preiotropic: i.e., cholinergic modulation of GABAergic synaptic transmission is differentially regulated depending on postsynaptic neuron subtypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Carbachol / pharmacology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Cholinergic Agonists / pharmacology*
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / physiology
  • Female
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Post-Synaptic Density / drug effects*
  • Rats
  • Rats, Transgenic
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Vesicular Inhibitory Amino Acid Transport Proteins / physiology*
  • gamma-Aminobutyric Acid / physiology*


  • Cholinergic Agonists
  • Slc32a1 protein, rat
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • gamma-Aminobutyric Acid
  • Carbachol