Comparison of the role of metabotropic glutamate receptor subtype 1 in developmental refinement of neuronal connectivity between the cerebellum and the sensory thalamus

Abstract

Developmental refinement of neuronal connectivity is crucial for proper brain function. In the early phase of development, input fibers arrive at their target areas guided by specific molecular cues and form abundant immature synapses. Then, functionally important synapses are preserved and strengthened by neural activity while unnecessary synapses are eliminated. Afferent synapses in the sensory thalamus, such as from retina to lateral geniculate nucleus, and climbing fiber (CF)−Purkinje cell (PC) synapses in the cerebellum are valuable models for studying this developmental refinement of synaptic connectivity because only a limited number of input fibers innervate a given postsynaptic thalamocortical (TC) neuron or PC. The metabotropic glutamate receptor subtype 1 (mGluR1) is required for the refinement of both afferent−TC neuron and CF−PC synapses. However, mGluR1 functions differently at these synapses. While mGluR1 is critical for elimination of surplus CF−PC synapses in the cerebellum, retinogeniculate synapses require mGluR1 for maintenance of mature connectivity.