Synchronous oscillatory activity in immature cortical network is driven by GABAergic preplate neurons.
Neurons dissociated from embryonic cerebral rat cortex form a differentiated network of synaptic connections and develop synchronous oscillatory network activity with the beginning of the second week in culture. During an initial phase lasting 3-4 d, synchronous calcium transients can be blocked completely by either CNQX or bicuculline, showing that both glutamatergic and GABAergic neurons are required for the generation of this form of activity. By manipulating dissociation and growth conditions, cultures containing different populations of GABAergic neurons were obtained. These cultures revealed that a distinct population of large GABAergic neurons is a key element in the generation of synchronous oscillatory network activity. A minimal number of two large GABAergic neurons per square millimeter are required for the occurrence of synchronous activity. Changes in the density of all other types of GABAergic or non-GABAergic neurons has no influence on the synchronous activity. Electron microscopic analysis shows that the large GABAergic neurons form an interconnected network. Exceptionally high somatodendritic innervation and extended axonal arborization enable these neurons to collect electric network activity and to distribute it effectively throughout the neuronal network. Additional experiments indicated that most neurons developing in culture to large GABAergic neurons are derived from the primordial plexiform layer and reside in the subplate at the time of birth. We suggest that they function as an integrating element that synchronizes neuronal activity during early cortical development by collecting incoming extrinsic and intrinsic signals and distributing them effectively throughout the developing cortical plate.
Voigt
T
T
Otto-von-Guericke Universität, Medizinische Fakultät, Institut für Physiologie, 39120 Magdeburg, Germany. Thomas.Voigt@Medizin.Uni-Magdeburg.de
Opitz
T
T
de Lima
A D
AD
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D002452:Cell Count; D019070:Cell Lineage; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; D018691:Excitatory Amino Acid Antagonists; D016326:Extracellular Matrix Proteins; D018755:GABA Agonists; D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D000091042:Reelin Protein; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D012697:Serine Endopeptidases