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

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

doi:10.1523/jneurosci.4591-03.2004

Cited by 34 publications

(30 citation statements)

References 59 publications

(75 reference statements)

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“…In addition to these behavioural changes, we found a large reduction in the level of Conflicting results have been obtained from binding studies and autoradiography [3,7,8], and functional studies have reported some inconsistent effects of A 2A receptor ligands [1,5,15,16,25,28,36]. mRNA for the A 2A receptor has been reported to be expressed in the dorsal root ganglion but not in the spinal cord [20,21] suggesting that A 2A receptors could be present on the peripheral terminals of the sensory nerves but not to any significant extent in the spinal cord, as suggested by Sawynok [32].…”

Section: Introductionsupporting

confidence: 45%

Genetic deletion of the adenosine A2A receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus

Hussey

Clarke

Ledent

et al. 2010

Neuroscience Letters

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Section: Introductionsupporting

confidence: 45%

Genetic deletion of the adenosine A2A receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus

Hussey

Clarke

Ledent

et al. 2010

Neuroscience Letters

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“…SPNs were identified electrophysiologically as described previously (Deuchars et al, 2001a,b;Brooke et al, 2004). IPSP amplitudes were measured as the peak changes from the holding potentials, averaged over 10 consecutive sweeps for control and drug responses, and are given as the mean Ϯ SEM.…”

Section: Discussionmentioning

confidence: 99%

“…The upper and middle thoracic spinal cord was removed and sectioned (250 m thick). Slices were then submerged in artificial CSF (aCSF) (in mM: 124 NaCl, 26 NaHCO 3 , 3 KCl, 2 MgSO 4 , 2.5 NaH 2 PO 4 , 2 CaCl 2 , and 10 glucose), equilibrated with 95% O 2 /5% CO 2 , and superfused at a rate of 3-5 ml/min as described previously (Deuchars et al, 2001a,b;Brooke et al, 2004). SPNs within the IML were targeted for these experiments, identified both electrophysiologically and anatomically as described previously (Deuchars et al, 2001a,b;Brooke et al, 2004).…”

Section: Electrophysiologymentioning

confidence: 99%

GABAergic Neurons in the Central Region of the Spinal Cord: A Novel Substrate for Sympathetic Inhibition

Deuchars¹,

Milligan²,

Stornetta³

et al. 2005

J. Neurosci.

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Homeostatic maintenance of widespread functions is critically dependent on the activity of the sympathetic nervous system. This activity is generated by the CNS acting on the sole output cells in the spinal cord, sympathetic preganglionic neurons (SPNs). SPNs are subject to control from both supraspinal and spinal inputs that exert effects through activation of direct or indirect pathways. A high proportion of indirect control is attributable to activation of spinal interneurons in a number of locations. However, little is known about the different groups of interneurons with respect to their neurochemistry or function. In this study, we report on a novel group of GABAergic interneurons located in the spinal central autonomic area (CAA) that directly inhibit SPN activity. In situ hybridization studies demonstrated a group of neurons that contained mRNA for glutamic acid decarboxylase (GAD) 65 and GAD 67 within the CAA. Combining in situ hybridization with trans-synaptic labeling from the adrenal gland using pseudorabies virus identified presympathetic GABAergic neurons in the CAA. Electrical stimulation of the CAA elicited monosynaptic IPSPs in SPNs located laterally in the intermediolateral cell column. IPSPs were GABAergic, because they reversed at the chloride reversal potential and were blocked by bicuculline. Chemical activation of neurons in the CAA hyperpolarized SPNs, an effect that was also bicuculline sensitive. We conclude that the CAA contains GABAergic interneurons that impinge directly onto SPNs to inhibit their activity and suggest that these newly identified interneurons may play an essential role in the regulation of sympathetic activity and thus homeostasis.

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“…However, the A 2A receptor gene does not appear to be expressed in the spinal cord (Kaelin-Lang et al, 1998) and autoradiographic techniques with selective A 2A receptor ligands, at concentrations well above K D values, confirm the absence of spinal cord receptor binding (Bailey et al, 2002). Despite this evidence, recent immunohistochemistry studies coupled with functional electrophysiology have shown responses to the A 2A selective agonist CGS 21680 in spinal cord (Brooke et al, 2004) and it has been proposed that these receptors are located on presynaptic inhibitory terminals of descending fibers from higher centers (Brooke et al, 2004). Thus, as for the central nervous system, the possibility of spinal effects of A 2A receptor activation cannot be completely excluded.…”

Section: Pain Circuitry and Localization Of Adenosine A 2a Receptorsmentioning

confidence: 99%

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

Ferré

Diamond

Goldberg

et al. 2007

Progress in Neurobiology

127

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Adenosine A 2A receptors localized in the dorsal striatum are considered as a new target for the development of antiparkinsonian drugs. Co-administration of A 2A receptor antagonists has shown a significant improvement of the effects of L-DOPA. The present review emphasizes the possible application of A 2A receptor antagonists in pathological conditions other than parkinsonism, including drug addiction, sleep disorders and pain. In addition to the dorsal striatum, the ventral striatum (nucleus accumbens) contains a high density of A 2A receptors, which presynaptically and postsynaptically regulate glutamatergic transmission in the cortical glutamatergic projections to the nucleus accumbens. It is currently believed that molecular adaptations of the cortico-accumbens glutamatergic synapses are involved in compulsive drug seeking and relapse. Here we review recent experimental evidence suggesting that A 2A antagonists could become new therapeutic agents for drug addiction. Morphological and functional studies have identified lower levels of A 2A receptors in brain areas other than the striatum, such as the ventrolateral preoptic area of the hypothalamus, where adenosine plays an important role in sleep regulation. Although initially believed to be mostly dependent on A 1 receptors, here we review recent studies that demonstrate that the somnogenic effects of adenosine are largely mediated by hypothalamic A 2A receptors. A 2A receptor antagonists could therefore be considered as a possible treatment for narcolepsy and other sleep-related disorders. Finally, nociception is another adenosine-regulated neural function previously thought to mostly involve A 1 receptors. Although there is some conflicting literature on the effects of agonists and antagonists, which may partly be due to the lack of selectivity of available drugs, the studies in A 2A receptor knockout mice suggest that A 2A receptor antagonists might have some therapeutic potential in pain states, in particular where high intensity stimuli are prevalent.

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

Cited by 34 publications

References 59 publications

Genetic deletion of the adenosine A2A receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus

Genetic deletion of the adenosine A2A receptor in mice reduces the changes in spinal cord NMDA receptor binding and glucose uptake caused by a nociceptive stimulus

GABAergic Neurons in the Central Region of the Spinal Cord: A Novel Substrate for Sympathetic Inhibition

Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry

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