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The Journal of Neuroscience, February 15, 1998, 18(4):1419-1427
Coordination of Neuronal Activity in Developing Visual Cortex by Gap Junction-Mediated Biochemical Communication
Karl Kandler and Lawrence C. Katz Howard Hughes Medical Institute and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710
During brain development, endogenously generated coordinated neuronal activity regulates the precision of developing synaptic circuits (; ). In the neonatal neocortex, a form of endogenous coordinated activity is present as locally restricted intercellular calcium waves that are mediated by gap junctions (). As in other neuronal and non-neuronal systems, these coordinated calcium fluctuations may form the basis of functional cell assemblies (for review, see ; ). In the present study, we investigated the cellular mechanisms that mediate the activation of neuronal domains and the propagation of intercellular calcium waves in slices from neonatal rat neocortex. The occurrence of neuronal domains did not depend on intercellular propagation of regenerative electrical signals because domains persisted after blockade of sodium and calcium-dependent action potentials. Neuronal domains were elicited by intracellular infusion of inositol trisphosphate (IP3) but not of calcium, indicating the involvement of IP3-related second-messenger systems. Pharmacological stimulation of metabotropic glutamate receptors, which are linked to the production of IP3, elicited similarly coordinated calcium increases, whereas pharmacological blockade of metabotropic glutamate receptors dramatically reduced the number of neuronal domains. Therefore, the propagating cellular signal that causes the occurrence of neuronal domains seems to be inositol trisphosphate but not calcium. Because coordination of neuronal calcium changes by gap junctions is independent of electrical signals, the function of gap junctions between neocortical neurons is probably to synchronize biochemical rather than electrical activity.
Key words: gap junction; visual cortex; inositol trisphosphate; calcium; metabotropic glutamate receptor; development; thapsigargin
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841419-09$05.00/0
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