Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor-mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor-mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor-mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.

Much of what is known about the organization of the superior colliculus is based on the arrangement of its external connections. Consequently, there is little information regarding pathways that remain intrinsic to it, even though recent data suggest that a horizontally oriented local circuit may mediate the functional reciprocity among fixation and saccade-related neurons. Therefore, the present experiments sought physiological evidence for neurons intrinsic to the superior colliculus that might participate in a horizontally oriented local circuit. Parasagittal slices of the ferret superior colliculus were prepared for in vitro recording, and 125 intermediate/deep layer neurons were examined in response to electrical stimulation rostral or caudal to the recording site. A substantial proportion (37%) of neurons responded with a prolonged period (means = 59.3 +/- 30 ms) of poststimulus suppression of spontaneous action potential activity. Of the suppressed neurons, most (53%) were disinhibited when the excitatory amino acid receptor antagonists D-2-amino-5-phosphonovaleric acid (D-APV) and 6-nitro-7 sulphamoylbeno[f]-quinoxaline-2,3-dione (NBQX) were administered, indicating that excitatory input to inhibitory interneurons was blocked. Of the neurons that received inputs from inhibitory interneurons, all had their suppressive responses decreased or eliminated by the gamma-aminobutyric acid antagonist, bicuculline. Finally, severing the superficial layers from the slice had no effect on intermediate layer responses to intrinsic stimulation. These data provide physiological evidence for the presence of horizontally oriented inhibitory interneurons in the superior colliculus. Furthermore, these findings are consistent with the hypothesis that an intrinsic circuit, routed through interneurons, might account for the reciprocal inhibition observed among fixation and saccade-related neurons.

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)

Fetal alcohol syndrome is a major cause of learning and sensory deficits. These disabilities may result from disruption of neocortex development and plasticity. Alcohol exposure during the third trimester equivalent of human gestation may have especially severe and long-lasting consequences on learning and sensory processing, because this is when the functional properties and connectivity of neocortical neurons start to develop. To address this issue, we used the monocular deprivation model of neural plasticity, which shares many common mechanisms with learning. Ferrets were exposed to ethanol (3.5 mg/kg, i.p.) on alternate days for 3 weeks starting on postnatal day (P) 10. Animals were then monocularly deprived at the peak of ocular dominance plasticity after a prolonged alcohol-free period (15-20 d). Quantitative single-unit electrophysiology revealed that alcohol exposure disrupted ocular dominance plasticity while preserving robust visual responses. Moreover, optical imaging of intrinsic signals revealed that the reduction in visual cortex area driven by the deprived eye was much less pronounced in ethanol-treated than in control animals. Alcohol exposure starting at a later age (P20) did not disrupt ocular dominance plasticity, indicating that timing of exposure is crucial for the effects on visual plasticity. In conclusion, alcohol exposure during a brief period of development impairs ocular dominance plasticity at a later age. This model provides a novel approach to investigate the consequences of fetal alcohol exposure and should contribute to elucidate how alcohol disrupts neural plasticity.