Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters.
We assessed the pathways by which excitatory and inhibitory neurotransmitters elicit postsynaptic changes in [Ca2+]i in brain slices of developing rat and cat neocortex, using fura 2. Glutamate, NMDA, and quisqualate transiently elevated [Ca2%]i in all neurons. While the quisqualate response relied exclusively on voltage-gated Ca2+ channels, almost all of the NMDA-induced Ca2+ influx was via the NMDA ionophore itself, rather than through voltage-gated Ca2+ channels. Glutamate itself altered [Ca2+]i almost exclusively via the NMDA receptor. Furthermore, synaptically induced Ca2+ entry relied almost completely on NMDA receptor activation, even with low-frequency stimulation. The inhibitory neurotransmitter GABA also increased [Ca2+]i, probably via voltage-sensitive Ca2+ channels, whereas the neuromodulator acetylcholine caused Ca2+ release from intracellular stores via a muscarinic receptor. Low concentrations of these agonists produced nonperiodic [Ca2+]i oscillations, which were temporally correlated in neighbouring cells. Optical recording with Ca2(+)-sensitive indicators may thus permit the visualization of functional networks in developing cortical circuits.
Yuste
R
R
Laboratory of Neurobiology, Rockefeller University, New York, New York 10021.
Katz
L C
LC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015220:Calcium Channels; D005971:Glutamates; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002217:Carbachol; D000109:Acetylcholine; D002118:Calcium