Novel vistas of calcium-mediated signalling in the thalamus

Abstract

Traditionally, the role of calcium ions (Ca(2+)) in thalamic neurons has been viewed as that of electrical charge carriers. Recent experimental findings in thalamic cells have only begun to unravel a highly complex Ca(2+) signalling network that exploits extra- and intracellular Ca(2+) sources. In thalamocortical relay neurons, interactions between T-type Ca(2+) channel activation, Ca(2+)-dependent regulation of adenylyl cyclase activity and the hyperpolarization-activated cation current ( I(h)) regulate oscillatory burst firing during periods of sleep and generalized epilepsy, while a functional triad between Ca(2+) influx through high-voltage-activated (most likely L-type) Ca(2+) channels, Ca(2+)-induced Ca(2+) release via ryanodine receptors (RyRs) and a repolarizing mechanism (possibly via K(+) channels of the BK(Ca) type) supports tonic spike firing as required during wakefulness. The mechanisms seem to be located mostly at dendritic and somatic sites, respectively. One functional compartment involving local GABAergic interneurons in certain thalamic relay nuclei is the glomerulus, in which the dendritic release of GABA is regulated by Ca(2+) influx via canonical transient receptor potential channels (TRPC), thereby presumably enabling transmitters of extrathalamic input systems that are coupled to phospholipase C (PLC)-activating receptors to control feed-forward inhibition in the thalamus. Functional interplay between T-type Ca(2+) channels in dendrites and the A-type K(+) current controls burst firing, contributing to the range of oscillatory activity observed in these interneurons. GABAergic neurons in the reticular thalamic (RT) nucleus recruit a specific set of Ca(2+)-dependent mechanisms for the generation of rhythmic burst firing, of which a particular T-type Ca(2+) channel in the dendritic membrane, the Ca(2+)-dependent activation of non-specific cation channels ( I(CAN)) and of K(+) channels (SK(Ca) type) are key players. Glial Ca(2+) signalling in the thalamus appears to be a basic mechanism of the dynamic and integrated exchange of information between glial cells and neurons. The conclusion from these observations is that a localized calcium signalling network exists in all neuronal and probably also glial cell types in the thalamus and that this network is dedicated to the precise regulation of the functional mode of the thalamus during various behavioural states.