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The Journal of Neuroscience, May 23, 2007, 27(21):5633-5642; doi:10.1523/JNEUROSCI.4647-06.2007

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Cellular/Molecular
Functional Characterization of Intrinsic Cholinergic Interneurons in the Cortex

Jakob von Engelhardt,¹ Marina Eliava,² Axel H. Meyer,³ Andrei Rozov,¹ and Hannah Monyer¹

¹Department Clinical Neurobiology, University of Heidelberg, 69120 Heidelberg, Germany, ²Department of Physiology, Northwestern University, Chicago, Illinois 60611, and ³Neuroscience Research, Abbott GmbH and Company KG, 67061 Ludwigshafen, Germany

Correspondence should be addressed to Hannah Monyer, Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364 69120 Heidelberg, Germany. Email: monyer{at}urz.uni-hd.de

Acetylcholine is a major neurotransmitter that modulates cortical functions. In addition to basal forebrain neurons that give rise to the principal cholinergic input into the cortex, a second source constituted by intrinsic cholinergic interneurons has been identified. Although these cells have been characterized anatomically, little is known about their functional role in cortical microcircuits. The paucity of this cell population has been a major hindrance for detailed electrophysiological investigations. To facilitate functional studies, we generated transgenic mice that express enhanced green fluorescent protein (EGFP) in choline acetyltransferase (ChAT)-positive neurons. Aided by the transgene expression, the characterization of distinct cholinergic interneurons was possible. These cells were located in layer 2–3, had a bipolar morphology, were calretinin- and vasoactive intestinal peptide positive, but had a non-GABAergic phenotype. Paired recordings showed that EGFP/ChAT-positive neurons receive excitatory and inhibitory input from adjacent principal cells and various types of interneurons. However, EGFP/ChAT-positive neurons do not exert direct postsynaptic responses in neighboring neurons. Interestingly, prolonged activation of EGFP-labeled cholinergic neurons induces an increase in spontaneous EPSCs in adjacent pyramidal neurons. This indirect effect is mediated by nicotinic receptors that are presumably presynaptically localized. Thus, intrinsic bipolar cholinergic neurons can modulate cortical function locally.

Key words: ChAT; acetylcholine receptor; nicotinic receptor; calretinin; VIP; BAC; EGFP; GABAergic neuron

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Received Oct. 26, 2006; revised March 27, 2007; accepted March 28, 2007.

Correspondence should be addressed to Hannah Monyer, Department of Clinical Neurobiology, University of Heidelberg, Im Neuenheimer Feld 364 69120 Heidelberg, Germany. Email: monyer{at}urz.uni-hd.de

Related articles in J. Neurosci.:

Illuminating Cholinergic Microcircuits in the Neocortex

Ludovic Tricoire and Christian Andres Cea-Del Rio
J. Neurosci. 2007 27: 12119-12120. [Full Text]  

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				P. Aracri, S. Consonni, R. Morini, M. Perrella, S. Rodighiero, A. Amadeo, and A. Becchetti Tonic Modulation of GABA Release by Nicotinic Acetylcholine Receptors in Layer V of the Murine Prefrontal Cortex Cereb Cortex, October 7, 2009; (2009) bhp214v1. [Abstract] [Full Text] [PDF]

				L. Tricoire and C. A. Cea-Del Rio Illuminating Cholinergic Microcircuits in the Neocortex J. Neurosci., November 7, 2007; 27(45): 12119 - 12120. [Full Text] [PDF]

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