Postnatal expression of glutamate decarboxylases in developing rat cerebellum

Abstract

The recent identification of two genes encoding distinct forms of the GABA synthetic enzyme, glutamate decarboxylase (GAD), raises the possibility that varying expression of the two genes may contribute to the regulation of GABA production in individual neurons. We investigated the postnatal development the two forms of GAD in the rat cerebellum. The mRNA for GAD67, the form which is less dependent on the presence of the cofactor, pyridoxal phosphate (PLP), is present at birth in presumptive Purkinje cells and increases during postnatal development. GAD67 mRNA predominates in the cerebellum. The mRNA for GAD65, which displays marked PLP-dependence for enzyme activity, cannot be detected in cerebellar cortex by in situ hybridization until P7 in Purkinje cells, and later in other GABA neurons. In deep cerebellar nuclei, which mature prenatally, both forms of GAD mRNA can be detected at birth. The amounts of immunoreactice GAD and GAD enzyme activity parallel changes in mRNA levels. We suggest that the delayed appearance of GAD65 is coincident with synapse formation between GABA neurons and their targets during the second postnatal week. GAD67 mRNA may be present prior to synaptogenesis to produce GABA for trophic and metabolic functions.

Expression of two forms of glutamic acid decarboxylase (GAD67 and GAD65) during postnatal development of rat somatosensory barrel cortex

“…The prolonged development of GAD67-and GAD65-positive puncta (synaptic terminals) agrees with quantitative results on GABA synapses that increase dramatically from very low levels at birth to reach adult numbers after 3 weeks of age (Micheva and Beaulieu, 1996). The delayed development of GAD65 relative to GAD67 has been observed in other systems (Greif et al, 1991(Greif et al, , 1992Guo et al, 1997).…”

“…A plausible hypothesis is that the two GADs play distinct roles during the maturation of the central nervous system. In support of this idea, recent evidence has shown that the two isoforms are expressed differentially during postnatal development in several brain areas (Greif et al, 1991(Greif et al, , 1992Guo et al, 1997). Additionally, the developmental kinetics of the two GADs and an alternatively spliced variant of GAD67 parallel neurogenesis and differentiation of the embryonic rat spinal cord (Behar et al, 1993;Somogyi et al, 1995).…”

Glutamatergic and GABAergic Neurotransmitter Cycling and Energy Metabolism in Rat Cerebral Cortex during Postnatal Development

“…In contrast, GABAergic synapses (synapses per neuron) expand rapidly from P10 to P30 (Micheva and Beaulieu, 1996). The observed increase in V cyc(GABA) (B7 Â ), V TCA(GABA) (B5 Â ), and V GAD (B5.5 Â ) closely parallels the reported percentage increase in total GAD activity of 400% to 470% in the neocortex from P10 to adulthood (Balcar et al, 1992), becoming increasingly associated (65-kd isoform) with nerve terminals (Greif et al, 1991). Thus, the increase in GABA-related fluxes between P10 and P30 appears to be similar to the expansion in the number of inhibitory synapses.…”

Development of “Pinceaux” formations and dendritic translocation of climbing fibers during the acquisition of the balance between glutamatergic and γ‐aminobutyric acidergic inputs in developing Purkinje cells

“…However, they are equipped with the appropriate vesicular transporter (VIAAT) to release GABA in a paracrine manner, and, because the nearby Purkinje cells express GABA A and GABA B receptors (Laurie et al, 1992;Fritschy et al, 1994;Lujan and Shigemoto, 2006), the released GABA might elicit a functional response in newborn Purkinje cells. Thus, postnatal Purkinje cells may respond to GABA release far before the formation of the first synapses with basket fibers (P7; Ango et al, 2004;present study) and before initiation of the expression of GABAergic markers other than VIAAT (McLaughlin et al, 1975;Greif et al, 1991;Yan and Ribak, 1998;Rosina et al, 1999;Takayama and Inoue, 2005).…”