Modulation of NMDA receptors in the cerebellum. II. Signaling pathways and physiological modulators regulating NMDA receptor function.

NMDA receptors in cerebellum have specific characteristics that make their function and modulation different from those of NMDA receptors in other brain areas. The properties of the NMDA receptor that modulate its function: Subunit composition, post-translational modifications and synaptic localization are summarized in an accompanying article. In this review we summarize how different signaling molecules modulate the function of NMDA receptors. The function of the receptors is modulated by the co-agonists glycine and serine and this modulation is different in cerebellum than in other areas. The NMDA receptor also has binding sites for polyamines that regulate its function. Other signaling molecules that modulate NMDA receptors function are: cAMP, neurotrophic factors such as BDNF, FGF-2 or neuregulins. These and other molecules allow an interplay between NMDA receptors and other receptors for neurotransmitters that may in this way modulate NMDA receptor function. This has been reported, for example, for metabotropic glutamate receptors. The expression and function of NMDA receptor is also modulated by synaptic activity, allowing an adaptation of the receptors function to the external inputs. NMDA receptors modulate important cerebral processes. NMDA receptors in different brain areas seem to modulate different processes. Cerebellar NMDA receptors play a special role in the modulation of motor learning and coordination. This is also briefly reviewed.