Messenger molecules in the cerebellum.

As data accumulate, the mammalian brain reveals its complex and subtle synaptic mechanisms. In the simplest system, a neurotransmitter binds to the receptor portion of a molecular complex incorporating an ion channel and thus alters the membrane potential, leading to excitatory or inhibitory effects. In more complex systems, receptors are coupled to second messenger systems to generate signals of longer duration and to modulate more diverse molecular mechanisms. The cerebellar cortex has a relatively simple wiring diagram with the primary neurotransmitter of most inhibitory and excitatory synapses well established. The second messenger signalling systems are more complex and those of the cerebellar output, the Purkinje cells, are the best characterized. More recently, molecules that might act as neuromodulators, carrying messages between neurons and between neurons and glial cells, have been identified, such as endothelin and nitric oxide. The classic neurotransmitters and novel neuromodulators, together with second messenger-activated trophic factors, can interact in complex ways; in this review Christopher Ross, David Bredt and Solomon Snyder discuss how studies of cerebellar circuitry and biochemistry are revealing such interrelations.