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The Journal of Neuroscience, January 7, 2004, 24(1):127-137; doi:10.1523/JNEUROSCI.4591-03.2004

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Behavioral/Systems/Cognitive
Input-Specific Modulation of Neurotransmitter Release in the Lateral Horn of the Spinal Cord via Adenosine Receptors

Ruth E. Brooke, Jim Deuchars, and Susan A. Deuchars

School of Biomedical Sciences, University of Leeds, Leeds LS2 9NQ, United Kingdom

Activation of adenosine A2_A receptors (A2_ARs) in the CNS produces a variety of neuromodulatory actions dependent on the region and preparation examined. In autonomic regions of the spinal cord, A1R activation decreases excitatory synaptic transmission, but the effects of A2_AR stimulation are unknown. We sought to determine the location and function of the A2_ARs in the thoracic spinal cord, focusing on the intermediolateral cell column (IML). A2_AR immunoreactivity was observed throughout the gray matter, with particularly dense immunostaining in regions containing sympathetic preganglionic neurons (SPNs), namely, the IML and intercalated nucleus. Electron microscopy revealed A2_AR immunoreactivity within presynaptic terminals and in postsynaptic structures in the IML. To study the functional relevance of these A2_ARs, visualized whole-cell patch-clamp recordings were made from electrophysiologically identified SPNs and interneurons within the IML. The A2_AR agonist c2-[p-(carboxyethyl)phenethylamino]-5'-N-ethylcarboxyamidoadenosine (CGS 21680) had no significant effect on EPSPs but increased the amplitude of IPSPs elicited by stimulation of the lateral funiculus. These effects were attributable to activation of presynaptic A2_ARs because CGS 21680 application altered the paired pulse ratio. Furthermore, neurons in the IML that have IPSPs increased via A2_AR activation also receive excitatory inputs that are inhibited by A1R activation. These data show that activating A2_ARs increase inhibitory but not excitatory transmission onto neurons in the IML. Simultaneous activation of A1Rs and A2_ARs therefore could facilitate inhibition of the postsynaptic neuron, leading to an overall reduction of sympathetic nervous activity.

Key words: adenosine; autonomic; immunoreactivity; patch clamp; spinal; sympathetic

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Received June 19, 2003; revised November 7, 2003; accepted November 11, 2003.

This article has been cited by other articles:

				E. Guntz, H. Dumont, E. Pastijn, A. de Kerchove d'Exaerde, K. Azdad, M. Sosnowski, S. N. Schiffmann, and D. Gall Expression of Adenosine A2A Receptors in the Rat Lumbar Spinal Cord and Implications in the Modulation of N-Methyl-d-Aspartate Receptor Currents Anesth. Analg., June 1, 2008; 106(6): 1882 - 1889. [Abstract] [Full Text] [PDF]

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				K.-i. Otsuguro, Y. Yamaji, M. Ban, T. Ohta, and S. Ito Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats J. Physiol., August 1, 2006; 574(3): 835 - 847. [Abstract] [Full Text] [PDF]

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