Postsynaptic Cell Type–Dependent Cholinergic Regulation of GABAergic Synaptic Transmission in Rat Insular Cortex

Abstract

Yamamoto K, Koyanagi Y, Koshikawa N, Kobayashi M. Postsynaptic cell type-dependent cholinergic regulation of GABAergic synaptic transmission in rat insular cortex. J Neurophysiol 104: 1933-1945. First published August 4, 2010 doi:10.1152/jn.00438.2010. 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 M) 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 carbacholinduced 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.

Spatiotemporal specificity in cholinergic control of neocortical function

“…suggested that this effect, together with the muscarinic and nicotinic increase in excitability of the layer V PCs resulted in the generation of Ca 2+ spikes and bursts of action potentials (APs) of the PCs when inputs in basal dendrites were stimulated [71]. Heterogeneous effects at FS cell terminals on INs, as well as on the terminals of non-identified ‘non FS cells’ on PCs were reported [91•,93]. …”

“… h Pronounced inhibition of GABA release at the presynaptic basket terminals of PV-expressing FS INs on PCs has been observed in somatosensory and insular cortices [91•,93], and Nunez et al . suggested that this effect, together with the muscarinic and nicotinic increase in excitability of the layer V PCs resulted in the generation of Ca 2+ spikes and bursts of action potentials (APs) of the PCs when inputs in basal dendrites were stimulated [71].…”

Functional neuromodulation of chemosensation in vertebrates

“…Evidence from GC recordings showing that ACh can decrease a cell's best response to a tastant while increasing its non-best responses to other tastants is consistent with such a rearrangement of taste coding [28] in response to behavioral state. This modulation could involve rearrangements of the balance between excitation and inhibition by cholinergic inputs: ACh reduces inhibitory transmission onto pyramidal cells and had mixed effects on connections between inhibitory interneurons in GC [29]. The final results of these changes would be a shift away from sparse taste representations (typically observed in anesthetized states) to dense, population-based, representations characteristic of wakefulness.…”

Spike Timing Rigidity Is Maintained in Bursting Neurons under Pentobarbital-Induced Anesthetic Conditions

“…All data were collected for the RMT analysis and have not been published elsewhere. The imbalance of the sample size between HFB and non-HFB neurons was caused by their population in the IC, as shown in our previous in vitro study (Yamamoto et al, 2010). Based on this study, we performed the following statistical tests without any correction.…”