An. Vandenpol et al., DEVELOPMENTAL REGULATION OF THE HYPOTHALAMIC METABOTROPIC GLUTAMATE-RECEPTOR MGLUR1, The Journal of neuroscience, 14(6), 1994, pp. 3816-3834
The expression of the metabotropic glutamate receptor mGluR1 was studi
ed with Northern and Western blot analysis, with immunocytochemistry,
and with Ca2+ digital imaging in the developing rat hypothalamus. mGlu
R1 is coupled to a G protein and activation by glutamate and related a
gonists leads to intracellular phosphotidylinositol hydrolysis and Ca2
+ mobilization. mGluR1 RNA could be detected in embryonic hypothalamus
, and by the day of birth and prior to the primary period of synaptoge
nesis, both mGluR1 RNA and protein were strongly expressed. In paralle
l experiments with digital imaging of cultured hypothalamic cells, som
e embryonic day 18 hypothalamic neurons and many astrocytes after 3 d
in vitro showed Ca2+ responses to quisqualate and t-ACPD, and to gluta
mate in the absence of extracellular Ca2+. A greater number of embryon
ic neurons responded to NMDA than to agonists of the metabotropic rece
ptor. With increased development time in culture, the number of neuron
s that responded to metabotropic glutamate receptor agonists increased
. In the adult hypothalamus, mGluR1-immunoreactive neurons were widesp
read, and particularly dense in the dorsomedial, lateral, and anterior
hypothalamus/preoptic areas, and in the mammillary body. Strongly imm
unoreactive cells were interspersed among neurons with no immunoreacti
vity. In developing neurons a diffuse immunostaining appeared along de
ndrites and somata. With time, beginning in the first week after birth
, strongly stained puncta appeared, possibly associated with synaptic
specializations. These puncta were numerous on dendrites of some adult
neurons, and were the most strongly,stained regions of neurons. Neuro
ns developing in vitro at low neuron densities showed a development of
mGluR1 immunoreactivity similar to that of neurons in vivo, but with
a delayed progression of immunostaining. We found no obvious staining
of axons or of astrocytes. A strong expression of mGluR1 protein was f
ound in the hypothalamus during the first 2 postnatal weeks; this expr
ession was partially reduced in adults. In contrast, cerebellum showed
no reduction in mGluR1 protein in adults. Together these data suggest
a complex regulation of mGluR1 during development, with sufficient ex
pression of functional receptors in the developing hypothalamus to mod
ulate morphogenesis and synaptogenesis, and later to play a role in tr
ansduction of glutamate signals in the adult. Different regions of the
brain showed dramatic differences in the way each expresses mGluR1 du
ring development.