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Notes: In the mature cerebral cortex the interhemispheric connections across the corpus callosum appear to be essentially completely excitatory on the basis of both immunocytochemical and electrophysiological studies. During late embryonic development, however, immunocytochemical staining reveals numerous GABA-positive fibres in the callosum, which later largely disappear. The origin of these fibres and whether they represent functional GABAergic neurons has not been established. In the present study we used a combination of retrograde labelling in vivo with electrophysiology and immnunocytochemistry in cell culture to show that transiently at birth in rat pups a substantial number of transcallosal cortical cells are functional GABAergic neurons. Possible roles and fates for these neurons are discussed.

Notes: Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, relatively little is known about the nature of the presynaptic properties. In the present study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouse barrel cortex. Using the conventional paired-pulse ratio (PPR) method, both AMPA and NMDA receptor-mediated PPR were observed during development. We found that the NMDA PPR increased gradually (thus, a reduction in Pr) from postnatal day (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We then used an additional method for assessing release probability, the observation of a progressive block of NMDA receptor-mediated EPSCs using MK-801. With this method, we were able to identify two classes of terminals with high or low probabilities of release. Interestingly, the higher release showed a reduction in probability during the critical period, consistent with the NMDA PPR results. We confirmed that the discrepancy between the NMDA and the AMPA PPR results was due to the existence of silent, or NMDA-only, synapses, as suggested in previous literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR discrepancy, we discuss the hypothesis that the terminals with transiently higher probability of release were found preferentially on silent synapses. Our results suggest that these presynaptic sites may also have an active role in plasticity by working concomitantly with postsynaptic sites during the critical period.

Notes: Optical recording with a voltage-sensitive dye was performed in visual cortical slices of the rat to determine the effect of acetylcholine (ACh) on the spread of excitation. In the presence of ACh, the spread of excitation initiated by stimulation at the white matter/layer VI (WM/VI) was greatly suppressed throughout the cortex, with less suppression in the middle layers. By comparing the effect of ACh with that of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the fraction of the synaptic component that was sensitive to ACh was evaluated. ACh suppressed ∼ 40–50% (maximum 55.8%, n = 11) of the initial synaptic component in the superficial and deep layers. In the middle, however, the effect was weakest and only ∼ 20–30% (minimum 20.9%, n = 11) of the initial synaptic component was suppressed. On the basis of histological analysis, the region with the weakest ACh effect extended from upper V to lower II/III. To identify the site of ACh action in terms of pre- versus postsynaptic localization, exogenous glutamate was applied. Because ACh did not suppress the excitation induced by glutamate, the site of the ACh action was indicated to be presynaptic. When layer II/III was stimulated instead of WM/VI, the suppression was uniform throughout the cortex. A muscarinic receptor antagonist, atropine, blocked the suppression by ACh. In conclusion, our results indicate the following two points. First, ACh strongly suppresses intracortical connectivity through presynaptic muscarinic receptors. Secondly, in contrast to the intracortical connection, some group(s) of fibres, possibly thalamocortical afferents that arise from white matter and terminate in the middle cortical layers are suppressed much less by ACh. While ACh has been reported to have confusingly diverse effects, e.g. direct depolarization and hyperpolarization as well as synaptic facilitation and suppression, its effect on the propagation of excitation is very clear; suppression on intracortical connection, leaving thalamocortical inputs rather intact. We postulate that cholinergic innervation enables the afferent input to have a relatively dominant effect in the cortex.