Presynaptic ionotropic receptors in the cerebellar cortex: Just the tip of the iceberg?

The presence of ionotropic receptors to neurotransmitters in presynaptic structures is well documented in many synapses of the mammalian brain. However, due to technical limitations, the actual prevalence of presynaptic ionotropic receptors, as well as their potential functional roles, have remained largely uncertain. The relatively simple and regular organization of neurites in the cerebellar cortex has offered a unique opportunity to bridge this gap of knowledge, by systematically probing the presence and role of presynaptic ionotropic receptors at various synapses. In the present review, we describe the collective results for glutamate and GABA presynaptic receptors in this brain region. They indicate a surprisingly large prevalence of presynaptic ionotropic receptors, with many synapses displaying several such receptors, often to both neurotransmitters. These results indicate that the presence of several types of presynaptic ionotropic receptors may be the rule rather than the exception in mammalian brain synapses. In addition, we discuss the functional roles of presynaptic ionotropic receptors in the induction of various forms of cerebellar long-term synaptic plasticity, as well as the potential consequences of having multiple presynaptic ionotropic receptors in a single synapse.