Glutamate-mediated responses in developing retinal ganglion cells.
Glutamate has been suggested to regulate the development of retinal ganglion cells, but little is known about the functional properties of glutamate receptors during ontogeny of these neurons. Using whole-cell and outside-out patch-clamp recordings, we have characterized the pharmacological, rectification, and kinetic properties of ionotropic glutamate receptors in ganglion cells isolated from fetal and postnatal cat retinas. The fetal cells were studied at embryonic day 33 (E33) to E38, before significant outgrowth of their dendritic processes and prior to the formation of synaptic contacts in the inner plexiform layer. In several respects, the functional properties of early fetal ganglion cells were found to be remarkably similar to those of postnatal cells. In both age groups, glutamate and AMPA produced fast desensitizing currents, kainate yielded large steady-state currents, while applications of NMDA resulted in multiple channel openings. The shapes and amplitudes of these glutamate-gated currents were also similar and the current-voltage relations were nearly linear, with reversal potentials near 0 mV. Moreover, the dose-response curves (to kainate) were virtually identical in the fetal and postnatal neurons. The proportion of neurons responsive to NMDA and non-NMDA agonists was nearly the same in both age groups. This early functional expression of glutamate receptors cannot be involved in the transmission of electrical information in the developing retina because at this stage few ganglion cells are capable of generating action potentials (Skaliora et al., 1993). It is suggested that the early activation of NMDA and non-NMDA receptors in fetal ganglion cells may regulate the outgrowth and stabilization of dendritic processes in these neurons. Our data also revealed some differences in the responses of fetal and postnatal cells to glutamate and its agonists. Thus, the unitary NMDA conductance was found to decrease with age, while the rate of glutamate receptor desensitization increased with age. Also, while virtually all postnatal cells responded to glutamate, the proportion of fetal cells that manifested glutamate-mediated responses was lower. These maturational changes presumably allow retinal ganglion cells to integrate synaptic inputs for the transmission of electrical signals to the visual centers of the brain.
Liets
L C
LC
Section of Neurobiology, Physiology, and Behavior, University of California, Davis, CA 95616, USA. lcliets@ucdavis.edu
Chalupa
L M
LM
D000818:Animals; D002415:Cats; D004553:Electric Conductivity; D004622:Embryo, Mammalian / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology; D017459:Receptors, Amino Acid / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology*
D007473:Ion Channels; D017459:Receptors, Amino Acid; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid