TY - JOUR
T1 - Adenosine is released during thalamic oscillations to provide negative feedback control
AU - Wall, Mark J.
AU - Puddefoot, Katie
AU - Yin, Wencheng
AU - Bingham, Chris
AU - Seifi, Mohsen
AU - Swinny, Jerome D.
AU - Ngomba, Richard Teke
N1 - Funding Information:
Work was perceived by MJW and RTN. Physiology experiments were performed by MJW, RTN and KP, with immunohistochemistry experiments carried out by JDS and MS. Physiology data was analysed by RTN, MJW, WY and CB. Paper was written by MJW and RTN. KP was an MIBTP funded PhD student. The work was funded by an ERUK pilot grant (PGE 1720) to MJW and RTN. The authors would like to thank Prof. Tom E. Salt (emeritus University College London) for reading an earlier version of the manuscript and for expert scientific comments.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/9/15
Y1 - 2022/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133229481&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2022.109172
DO - 10.1016/j.neuropharm.2022.109172
M3 - Article
AN - SCOPUS:85133229481
SN - 0028-3908
VL - 216
JO - Neuropharmacology
JF - Neuropharmacology
M1 - 109172
ER -