Elsevier

Neuroscience

Volume 88, Issue 4, February 1999, Pages 1213-1223
Neuroscience

A novel influence of adenosine on ongoing activity in rat rostral ventrolateral medulla

https://doi.org/10.1016/S0306-4522(98)00296-6Get rights and content

Abstract

We have investigated whether exogenously applied adenosine modulates neuronal activity in a region of the central nervous system crucial for cardiovascular regulation. Extracellular recordings were made from neurons in the rostral ventrolateral medulla of the anaesthetized rat. Ionophoretic application of adenosine altered ongoing activity in 91% of neurons, evoking either a long-lasting depression or a short-lasting increase in firing rate. Both responses were blocked by application of the broad spectrum adenosine receptor antagonist 8-sulphophenyltheophylline, indicating that the responses were mediated by specific cell surface receptors. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine blocked the increase, and partially blocked the decrease in firing rate in response to adenosine. The GABAA receptor antagonist bicuculline also blocked the increase in firing rate in response to adenosine suggesting that adenosine may inhibit release of GABA from axon terminals in this region. The adenosine A2a receptor agonist CGS 21680 produced a long-lasting depression of ongoing activity. These results suggest A1 receptors mediate an increase in firing rate, whilst A1 and A2a receptors mediate decreases in firing rate in some rostral ventrolateral medulla neurons. Thus, adenosine has been shown to modulate the ongoing activity of neurons in the rostral ventrolateral medulla by acting at both A1 and A2a receptors.

Accordingly we suggest, and provide some evidence to support the idea, that adenosine acts as an important neuromodulator in this region of the central nervous system, possibly by modulating the presynaptic release of neurotransmitters such as GABA.

Section snippets

General methods

Experiments were performed on 32 male Sprague–Dawley rats (260–320 g; Royal Free Hospital, Comparative Biology Unit). Anaesthesia was induced with pentobarbitone sodium (Sagatal, May & Baker; 60 mg/kg, i.p.) and supplemented as necessary with α-chloralose (5 mg/kg, i.v.). During the surgery, anaesthesia was maintained such that a strong pinch of the paw did not evoke withdrawal of the paw and there were no spontaneous movements. All of the following procedures and protocols were carried out in

General details

This study reports on a total of 55 neurons recorded within the region of the RVLM as described anatomically by Paxinos and Watson.[15] Ten of the recorded neurons were identified as bulbospinal in that the evoked action potential on stimulation within the thoracic spinal cord had a constant latency (mean 6±1.6 ms, range 2–19 ms) and could be cancelled by collision with an ongoing occurring action potential (see Fig. 1A). The mean axonal conduction velocity of these neurons was 5±0.9 m/s.

Discussion

In the present study, neurons with a variety of electrophysiological characteristics, and inputs, have been investigated from the region of the RVLM. We have shown that ionophoretic application of adenosine and/or an adenosine receptor agonist can alter ongoing activity of these neurons and our observations suggest that several adenosine receptor subtypes are active in this region.

Some of these neurons were shown also to be spinally projecting and had some characteristics consistent with them

Conclusions

We have shown that the activity of neurons in the RVLM is modulated by adenosine acting at P1 receptors. These effects may involve more than one receptor subtype, and are likely to be mediated by an effect on neurotransmitter release in this region of the brainstem. Our data indicate that adenosine appears to have little tonic effect on RVLM neurons, since ionophoresis of adenosine receptor antagonists did not alter ongoing activity. Adenosine has long been termed a “retaliatory metabolite” and

Unlinked References

[27] is not cited in the text.[29] is not cited in the text.

Acknowledgements

We thank Miss Linda Hutchinson for technical assistance. This work was supported by the British Heart Foundation. CGS 21680 sodium salt was donated by Ciba Geigy.

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