Adenosine is released during thalamic oscillations to provide negative feedback control

Mark J. Wall*, Katie Puddefoot, Wencheng Yin, Chris Bingham, Mohsen Seifi, Jerome D. Swinny, Richard Teke Ngomba

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    30 Downloads (Pure)

    Abstract

    Physiological oscillations in the cortico-thalamo-cortical loop occur during processes such as sleep, but these can become dysfunctional in pathological conditions such as absence epilepsy. The purine neuromodulator adenosine can act as an endogenous anticonvulsant: it is released into the extracellular space during convulsive seizures to activate A1 receptors suppressing on-going activity and delaying the occurrence of the next seizure. However, the role of adenosine in thalamic physiological and epileptiform oscillations is less clear. Here we have combined immunohistochemistry, electrophysiology, and fixed potential amperometry (FPA) biosensor measurements to characterise the release and actions of adenosine in thalamic oscillations measured in rodent slices. In the thalamus, A1 receptors are highly expressed particularly in the ventral basal (VB) thalamus and reticular thalamic nucleus (nRT) supporting a role for adenosine signalling in controlling oscillations. In agreement with previous studies, both adenosine and adenosine A1 receptor agonists inhibited thalamic oscillations in control (spindle-like) and in epileptic conditions. Here we have shown for the first time that both control and epileptiform oscillations are enhanced (i.e., increased number of oscillatory cycles) by blocking A1 receptors consistent with adenosine release occurring during oscillations. Although increases in extracellular adenosine could not be directly detected during control oscillations, clear increases in adenosine concentration could be detected with a biosensor during epileptiform oscillation activity. Thus, adenosine is released during thalamic oscillations and acts via A1 receptors to feedback and reduce thalamic oscillatory activity.

    Original languageEnglish
    Article number109172
    Number of pages13
    JournalNeuropharmacology
    Volume216
    Early online date2 Jul 2022
    DOIs
    Publication statusPublished - 15 Sept 2022

    Fingerprint

    Dive into the research topics of 'Adenosine is released during thalamic oscillations to provide negative feedback control'. Together they form a unique fingerprint.

    Cite this