title: Gq/11-induced and spontaneous waves of coordinated network activation in developing frontal cortex.
abstract: Repeated episodes of spontaneous large-scale neuronal bursting and calcium influx in the developing brain can potentially affect such fundamental processes as circuit formation and gene expression. Between postnatal day 3 (P3) and P7, the immature cortex can express one such form of activation whereby a wave of neuronal activity propagates through cortical networks, generating massive calcium influx. We previously showed that this activity could be triggered by brief stimulation of muscarinic receptors. Here, we show, by monitoring large cortical areas at low magnification, that although all areas respond to muscarinic agonists to some extent, only some areas are likely to generate the coordinated wave-like activation. The waves can be triggered repeatedly in frontal areas where, as we also show, waves occur spontaneously at a low frequency. In parietal and occipital areas, no such waves are seen. This selectivity may be related in part to differences in the cortical distribution of dopaminergic signaling, because we find that activation of dopamine receptors enables the response. Because M1 muscarinic receptors are typically coupled with G-alpha(q)/11, we investigated whether other receptors known to couple with this G-protein (group I glutamate metabotropic receptors, neurotensin type 1) could similarly elicit wave-like activation in responsive cortical areas. Our results suggest that multiple neurotransmitter systems can enable this form of activation in the frontal cortex. The findings suggest that a poorly recognized, developmentally regulated form of strong network activation found predominantly in the frontal cortex could potentially exert a profound influence on brain development.
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: D Paola
authors.initials: DP
authors.lastname: Calderon
authors.forename: Natalya
authors.initials: N
authors.lastname: Leverkova
authors.forename: Alejandro
authors.initials: A
authors.lastname: Peinado
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D005625:Frontal Lobe / Q000254:growth & development / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D009116:Muscarine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology; D009778:Occipital Lobe / Q000254:growth & development; D010296:Parietal Lobe / Q000254:growth & development; D010446:Peptide Fragments / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D043643:Receptor, Muscarinic M1 / Q000187:drug effects / Q000502:physiology; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors
chemical_list: D000109:Acetylcholine; D001552:Benzazepines; D004298:Dopamine; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D018698:Glutamic Acid; D007189:Indans; D009116:Muscarine; D009419:Nerve Tissue Proteins; D009496:Neurotensin; D010446:Peptide Fragments; D010617:Phenanthridines; D010852:Picrotoxin; D064529:Receptor, Metabotropic Glutamate 5; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; C095756:1-aminoindan-1,5-dicarboxylic acid; C042090:neuromedin N; C061532:dihydrexidine; C054381:neurotensin (8-13)
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