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The Journal of Neuroscience, August 1, 2007, 27(31):8324-8333; doi:10.1523/JNEUROSCI.0638-07.2007

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Behavioral/Systems/Cognitive
The Neurochemically Diverse Intermedius Nucleus of the Medulla as a Source of Excitatory and Inhibitory Synaptic Input to the Nucleus Tractus Solitarii

Ian J. Edwards,^1 * Mark L. Dallas,^1 * Sarah L. Poole,¹ Carol J. Milligan,¹ Yuchio Yanagawa,² Gábor Szabó,³ Ferenc Erdélyi,³ Susan A. Deuchars,¹ and Jim Deuchars¹

¹Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom, ²Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, and Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Maebashi 371-8511, Japan, and ³Department of Gene Technology and Developmental Neurobiology, Institute of Experimental Medicine, H-1450 Budapest, Hungary

Correspondence should be addressed to either Jim Deuchars or Susan A. Deuchars, Institute of Membrane and Systems Biology, Garstang Building, University of Leeds, Leeds LS2 9JT, UK. Email: J.Deuchars{at}leeds.ac.uk or Email: S.A.Deuchars{at}leeds.ac.uk

Sensory afferent signals from neck muscles have been postulated to influence central cardiorespiratory control as components of postural reflexes, but neuronal pathways for this action have not been identified. The intermedius nucleus of the medulla (InM) is a target of neck muscle spindle afferents and is ideally located to influence such reflexes but is poorly investigated. To aid identification of the nucleus, we initially produced three-dimensional reconstructions of the InM in both mouse and rat. Neurochemical analysis including transgenic reporter mice expressing green fluorescent protein in GABA-synthesizing neurons, immunohistochemistry, and in situ hybridization revealed that the InM is neurochemically diverse, containing GABAegric and glutamatergic neurons with some degree of colocalization with parvalbumin, neuronal nitric oxide synthase, and calretinin. Projections from the InM to the nucleus tractus solitarius (NTS) were studied electrophysiologically in rat brainstem slices. Electrical stimulation of the NTS resulted in antidromically activated action potentials within InM neurons. In addition, electrical stimulation of the InM resulted in EPSPs that were mediated by excitatory amino acids and IPSPs mediated solely by GABA_A receptors or by GABA_A and glycine receptors. Chemical stimulation of the InM resulted in (1) a depolarization of NTS neurons that were blocked by NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonoamide) or kynurenic acid and (2) a hyperpolarization of NTS neurons that were blocked by bicuculline. Thus, the InM contains neurochemically diverse neurons and sends both excitatory and inhibitory projections to the NTS. These data provide a novel pathway that may underlie possible reflex changes in autonomic variables after neck muscle spindle afferent activation.

Key words: posture; neck; cardiovascular; respiration; medulla oblongata; autonomic

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Received Feb. 13, 2007; revised May 25, 2007; accepted June 20, 2007.

Correspondence should be addressed to either Jim Deuchars or Susan A. Deuchars, Institute of Membrane and Systems Biology, Garstang Building, University of Leeds, Leeds LS2 9JT, UK. Email: J.Deuchars{at}leeds.ac.uk or Email: S.A.Deuchars{at}leeds.ac.uk

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