Modulation by somatostatin of glutamate sensitivity during development of mouse hypothalamic neurons in vitro.
Glutamate sensitivity development and interactions of somatostatin (SRIF) with AMPA/Kainate receptor-mediated glutamate responses were studied in dissociated hypothalamic neurons from 16-day-old mouse embryos grown in vitro. Only 18% of functionally innervated cells could be found at 6-9 DIV whereas the percentage of innervated neurons progressively increased thereafter to reach 100% at 19-22 DIV. The glutamate sensitivity, estimated from glutamate-induced peak inward current, was very low at 6-9 DIV, sharply increased at 11-14 DIV and developed at a low increase rate thereafter. SRIF either unaffected glutamate peak current (27% of the cells), or significantly decreased (50%) or increased it (23%). Pertussis Toxin pretreatment abolished the SRIF-induced decrease of the glutamate response without affecting the excitatory effect. The number of glutamate responsive neurons inhibited by SRIF increased with time in culture whereas that of neurons responding to SRIF by an increased glutamate response was not statistically modified by functional innervation. The present data suggest that increased glutamate sensitivity coincides with the onset of functional synaptogenesis in mouse hypothalamic neurons in culture. SRIF can modulate glutamate sensitivity of hypothalamic neurons with either synergistic or antagonistic effects. Since glutamate has been shown to stimulate SRIF synthesis and secretion from hypothalamic neurons, the reverse capacity of SRIF to modulate the glutamate response suggests that both transmitters exhibit complex reciprocal interactions.
Gardette
R
R
INSERM U159, Paris, France.
Faivre-Bauman
A
A
Loudes
C
C
Kordon
C
C
Epelbaum
J
J
D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence; D004351:Drug Resistance; D004357:Drug Synergism; D018698:Glutamic Acid / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D013569:Synapses / Q000502:physiology
D018698:Glutamic Acid; D013004:Somatostatin