Two Types of Nicotinic Receptors Mediate an Excitation of Neocortical Layer I Interneurons

Abstract

Nicotinic acetylcholine receptors are widely expressed in the neocortex but their functional roles remain largely unknown. Here we investigated the effect of nicotinic receptor activation on interneurons of layer I, which contains a high density of cholinergic fiber terminals. Ninety-seven of 101 neurons recorded in whole cell configuration in rat acute slices were excited by local pressure application of nicotinic agonists, acetylcholine (500 microM), 1,1-dimethyl-4-phenyl-piperazinium (500 microM) or choline (10 mM). Biocytin labeling confirmed that our sample included different morphological types of layer I interneurons. The responses to nicotinic agonists persisted in presence of glutamate and muscarinic receptor antagonists and on further addition of Cd(2+) or tetrodotoxin, indicating that they were mediated by direct activation of postsynaptic nicotinic receptors. The kinetics of the currents and their sensitivity to nicotinic receptor antagonists, methyllycaconitine (1-10 nM) or dihydro-beta-erythroidine (500 nM), suggested that early and late components of the responses were mediated by alpha7 and non-alpha7 types of receptors. Both components had inwardly rectifying I-V curves, which differed when intracellular spermine was omitted. Single-cell RT-PCR experiments identified alpha4, alpha7, and beta2 as the predominantly expressed mRNAs, suggesting that the receptors consisted of alpha7 homomers and alpha4beta2 heteromers. Finally, selective excitation of layer I interneurons through activation of their nicotinic receptors resulted in a tetrodotoxin-sensitive increase of inhibitory synaptic currents recorded in nonpyramidal cells but not in pyramidal cells of layer II/III. These results suggest that acetylcholine released in layer I may induce a disinhibition of the cortical network through activation of nicotinic receptors expressed by layer I interneurons.

Sodium salicylate suppresses serotonin-induced enhancement of GABAergic spontaneous inhibitory postsynaptic currents in rat inferior colliculus in vitro

“…Moreover, the GABA neuron is modeled to be modulated only by the serotonergic system for simplicity although the GABAergic synaptic transmissions can also be influenced by other neural modulators such as the adrenergic (Bennett et al, 1998), dopaminergic (Gao et al, 2003;Gorelova et al, 2002) and cholinergic (Christophe et al, 2002;Yigit et al, 2003) systems. The glutamate neuron is not modeled to be under the influence of the serotonergic system, although 5-HT receptors are expressed in both GABA and non-GABA neurons in the inferior colliculus (Peruzzi and Dut, 2004).…”

Nicotinic Acetylcholine Receptors in Sensory Cortex: Figure 1

“…In brain slices from motor cortex, parietal association cortex, and hippocampus, nicotinic agonists exert negligible direct actions on pyramidal/principal neurons (however, see Ji et al 2001) but strongly excite GABAergic and other local circuit neurons via non-␣7 and, especially, ␣7 nAChRs; this action could, in turn, strongly inhibit pyramidal neurons (Jones and Yakel 1997;Frazier et al 1998bFrazier et al , 2003Porter et al 1999;Alkondon et al 2000;Ji and Dani 2000;Ji et al 2001;Christophe et al 2002).…”

“…These GABAergic interneurons preferentially project to the upper cortical layers, and would be expected to inhibit pyramidal neurons within the same cortical "column" when excited. Interneurons in layer 1 have been studied in slices from the somatosensory cortex of 2-to 3-week-old rats (Christophe et al 2002). Layer 1 has a particularly rich innervation of cholinergic axons and putative synapses (Mechawar et al 2000).…”

Task-phase-specific dynamics of basal forebrain neuronal ensembles

“…First, modulation of cortical responsiveness by BF can be mediated by at least three neurochemical forms, as projection neurons may be acetylcholinergic, glutamatergic, or GABAergic (Brückner et al, 1994; Metherate and Ashe, 1995; Gritti et al, 1997; Zaborszky et al, 1999; Riedel et al, 2002; Sarter and Bruno, 2002; Nelson et al, 2005; Henny and Jones, 2008). In turn, each neurochemical system maintains a unique set of synaptic targets within any cortical region with, for example, the GABAergic projection predominantly synapsing upon GABAergic interneurons of the neocortex (Kawaguchi, 1997; Xiang et al, 1998; Porter et al, 1999; Christophe et al, 2002; Henny and Jones, 2008). Second, different BF nuclei, and even different individual neurons in any one nucleus, innervate different sub-regions of neocortex (Bigl et al, 1982; Rigdon and Pirch, 1984, 1986; Kristt et al, 1985; Zahm et al, 1996; Zaborszky et al, 1999, 2013).…”