Developmental changes in the localisation of the mGluR1α subtype of metabotropic glutamate receptors in Purkinje cells

Abstract

The regulation of neurotransmitter receptors during synapse formation has been studied extensively at the neuromuscular junction, but little is known about the development of excitatory neurotransmitter receptors during synaptogenesis in central synapses. In this study we show qualitatively and quantitatively that a receptor undergoes changes in localisation on the surface of rat Purkinje cells during development in association with its excitatory synapses. The presence of mGluR1α at parallel and climbing fibre synapses on developing Purkinje cells was studied using high-resolution immunoelectron microscopy. Immunoreactivity for mGluR1α was detected from embryonic day 18 in Purkinje cells, and showed dramatic changes in its localisation with age. At early postnatal ages (P0 and P3), mGluR1α was found both in somata and stem dendrites but was not usually associated with synaptic contacts. At P7, mGluR1α became concentrated in somatic spines associated with climbing fibres and in the growing dendritic arborisation even before innervation by parallel fibres. During the second and third postnatal week, when spines and parallel fibre synapses were generated, mGluR1α became progressively concentrated in the molecular layer, particularly in the synaptic specialisations. As a result, during the fourth postnatal week, the pattern and level of mGluR1α expression became similar to the adult and mGluR1α appeared in high density in perisynaptic sites. Our results indicate that mGluR1α is present in the developing Purkinje cells prior to their innervation by climbing and parallel fibres and demonstrate that this receptor undergoes a dynamic and specific regulation during postnatal development in association with the establishment of synaptic inputs to Purkinje cell.