Purinergic modulation of granule cells.

Extracellular purines exert their action in the nervous system through purinergic neurotransmission and neuromodulatory processes. Among brain areas, efforts have been made to investigate the purinergic modulation of the cerebellar cortex. In addition, the use of granule cells in culture as a neuronal in vitro model provided important information about the implications of purines in mechanisms such as cell survival and differentiation. This short review is focused on the function of purines in the physiology of granule cells in situ and in vitro. In situ, adenosine has been shown to inhibit some of the glutamatergic and GABAergic synaptic inputs to granule cells. The inhibition of GABA input allows an increase in the excitability of the cell while the output (parallel fibers) of granule cells is also down-regulated by adenosine, suggesting a complex mode of regulation by purines. In vitro, granule cells have been shown to express members of all classes of purinergic receptors, P2X (ionotropic), P2Y (metabotropic) and adenosine receptors. The specific expression of these receptors and the downstream signaling pathways coupling them to cell survival and growth have been extensively studied.