Brain Research, 111 (1976) 119-133 119 © ElsevierScientific PublishingCompany,Amsterdam- Printed in The Netherlands NEUROCHEMICAL ASPECTS OF THE ONTOGENESIS OF GABANERGIC NEURONS IN THE RAT BRAIN J. T. COYLE and S. J. ENNA Departments of Pharmacology and Experimental Therapeutics and Psychiatry and the Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Md. 21205 (U.S.A.) (Accepted December 12th, 1975) SUMMARY Examination of various biochemical characteristics of the GABAnergic nervous system in the rat brain was made between 15 days of gestation and adulthood. At birth, the concentration of GABA in whole brain and most regions is approximately 50 ~ of adult levels, whereas the medulla-pons has achieved adult levels by this time. Compared to GABA levels, there is a marked lag in the development of the activity of glutamic acid decarboxylase in all areas studied; however, the activity of the enzyme increases in a linear fashion from birth to adulthood. The development of the uptake of GABA into particulate fractions prepared from whole brain and regions differs markedly from that of GABA and glutamic acid decarboxylase, with uptake near adult levels by birth, peaking considerably above that of the adult between one to two weeks after birth and then declining toward adult activity by 4 weeks after birth. Examination of the kinetics of GABA uptake into resuspended P2 fractions demonstrates that the developmental changes in the uptake reflects differences in the Vmax whereas the Kt remains constant. Studies on the development of the apparent postsynaptic receptor for GABA reveals that in all regions binding is approximately 25 ~ of adult up to 8 days after birth, at which time it increases dramatically, approx- imating adult levels by 4 weeks after birth. The rise in the density of the apparent post- synaptic GABA receptor after 8 days postpartum correlates best with the increase in the activity of glutamic acid decarboxylase, a presynaptic marker. INTRODUCTION The functional activity of a neuronal pathway depends upon the interaction of numerous variables such as neurotransmitter synthesis, storage, release, uptake, degradation and the number of postsynaptic receptor sites on adjacent neurons.