Mechanism of synapse elimination during circitogenesis of developing brain

Research Project

Project/Area Number	14580773
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Neuroscience in general
Research Institution	JIKEI UNIVERSITY SCHOOL OF MEDICINE
Principal Investigator	KAWAI Yoshinori Jikei University School of Medicine, Professor, 医学部, 教授 (80211861)
Project Period (FY)	2002 – 2003
Project Status	Completed (Fiscal Year 2003)
Budget Amount *help	¥3,400,000 (Direct Cost: ¥3,400,000) Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000) Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywords	synapse elimination / GABA / GABAA-type receptor / nucleus tractus solitarius / development / neuronal circuit / subunit
Research Abstract	gammna-aminobutyric acid (GABA) is a main inhibitory neurotransmitter in the central nervous system and thought to be critically involved in regulating excitatory neurotransmission. For the' inhibitory neurotransmission, GABA-A receptors, a pentameric hetero-oligomer ligand-gated chloride channel consisting mainly of alpha, beta and gamma subunits, must be clustered at the~postsynaptic membranes. In the present study, how GABAergic synaptic activity and expression of molecules responsible for the receptor-mediated transmission are regulated and correlated with each other during development, was addressed in the caudal nucleus of the tractus solitarius (NTS). GABAergic inhibitory postsynaptic currents (IPSCs) and expression of GABA-A receptor gamma1 subunit, which is reported to be essential for the receptor clustering at the postsynaptic membranes, were consistently evident in small-sized neurons of the caudal NTS during the early postnatal period (P1-6). After the first postnatal week, both IPSCs and expression of GABA-A receptor gamma 1 subunit virtually disappeared in these neurons. Low-level expression of GABAA receptor gamma2 subunit and gephyrin were consistently observed in the NTS. Electron microscopy revealed that number of GABAergic axosomatic synapses was drastically decreased during the development. Pharmacological properties of evoked GAI3A currents suggest a conversion of GABA-A receptor subunit configurations from alpha/beta/gamma to alpha/beta in small-sized neurons. These results show that GABAergic synaptic activity and gamma1 subunit expression were well correlated with each other and regulated developmentally in specific type of NTS neurons to establish the local neuronal networks of adult type. This phenomenon may underlie an establishment of cardiovascular and respiratory reflex circuits in the medulla.