Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections

Abstract

Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2–3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron.(ABSTRACT TRUNCATED AT 250 WORDS)

A Role for Nitric Oxide in the Development of the Ferret Retinogeniculate Projection

“…Whereas presynaptic NMDA receptors may be present in visual cortex (Aoki et al, 1994), there is no evidence for their presence in the LGN. Physiological evidence suggests that NMDA receptors are postsynaptic, because holding postsynaptic LGN cells at hyperpolarizing membrane potentials reduces the NMDA component of the postsynaptic current (Esguerra et al, 1992;Ramoa and McCormick, 1994). Additionally, the NMDA antagonist D-APV selectively inhibits the NMDA receptor-mediated component of retinogeniculate EPSPs (Esguerra et al, 1992).…”

“…Postsynaptic NMDA receptors contribute significantly to retinogeniculate synaptic transmission (Sillito et al, 1990;Kwon et al, 1991;Esguerra et al, 1992;Ramoa and McCormick, 1994). NMDA receptor antagonists infused into the ferret LGN disrupt the pattern of sublamination of presynaptic retinogeniculate axons; retinal ganglion cell axon arbors are either abnormally large or are restricted in size but terminate in inappropriate locations within the LGN (Hahm et al, 1991).…”

Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse

“…thus relieving the magnesium blockade of the NMDA receptor (Mayer et al, 1984;Nowak et al, 1984); (3) development of the intrinsic membrane properties in the immature neuron may be coordinated to enhance excitatory transmission related to retinal activity (Ramoa and McCormick. 1994): and (4) finally, the kinetic properties, but not the voltage dependence, ofthe NMD.4 response itself may be altered during de\,clopment so as to increase the duration of the EPSPs.…”

“…Preparations were as described in the preceding companion article (Ramoa and McCormick, 1994), except that in some experiments, noted in the text and in the figure captions, the concentration of MgSO, was raised to 4 mM. Recordings were conducted in the current-clamp mode at a temperature of 32"C, and in the voltage-clamp mode at a temperature of 22°C.…”

“…Thalamic slices were obtained from animals ranging in age from day of birth (postnatal day 0, PO), when retinogeniculate connections are diffuse and intermixed (Linden et al,198 l), until P54, after morphologically mature cell types can be recognized in the LGNd (Sutton and Brunso-Bechtold, 199 l), retinogeniculate connections have segregated according to eye of origin (Linden et al,198 l), eyelids have opened, and mature electrophysiological properties of LGNd cells have been established (Ramoa and McCormick, 1994). We were especially interested in examining the relative contribution and properties of NMDA receptor-mediated responses to retinogeniculate synaptic activation in the developing LGNd, and the regulation of this by GABAergic inhibition.…”