Temporal Course of Transient Direct Corticomotoneuronal Connections during Development in Rodents.

We previously observed in rodents that during the 2nd postnatal week corticospinal axons make monosynaptic connections with motoneurons. Prior to that finding, it had been believed that such contacts only occur in higher primates. Although an in vitro electrophysiological study is prerequisite for studying the developmental time course of synaptic connections, the technical difficulty of reliably recording synaptic responses from spinal motoneurons in animals over 2 weeks old hampered the study.

Higher primate-like direct corticomotoneuronal connections are transiently formed in a juvenile subprimate mammal.

The corticospinal (CS) tract emerged and evolved in mammals, and is essentially involved in voluntary movement. Over its phylogenesis, CS innervation gradually invaded to the ventral spinal cord, eventually making direct connections with spinal motoneurons (MNs) in higher primates. Despite its importance, our knowledge of the origin of the direct CS-MN connections is limited; in fact, there is controversy as to whether these connections occur in subprimate mammals, such as rodents.

The decline in synaptic GluN2B and rise in inhibitory neurotransmission determine the end of a critical period.

Neuronal plasticity is especially active in the young, during short windows of time termed critical periods, and loss of a critical period leads to functional limitations in the adults. The mechanism that governs the length of critical periods remains unknown. Here we show that levels of the NMDA receptor GluN2B subunit, which functions as a Ca channel, declines in spinal cord synapses toward the end of the critical period for activity-dependent corticospinal synapse elimination.

Specific involvement of postsynaptic GluN2B-containing NMDA receptors in the developmental elimination of corticospinal synapses.

The GluN2B (GluRepsilon2/NR2B) and GluN2A (GluRepsilon1/NR2A) NMDA receptor (NMDAR) subtypes have been differentially implicated in activity-dependent synaptic plasticity. However, little is known about the respective contributions made by these two subtypes to developmental plasticity, in part because studies of GluN2B KO [Grin2b(-/-) (2b(-/-))] mice are hampered by early neonatal mortality. We previously used in vitro slice cocultures of rodent cerebral cortex (Cx) and spinal cord (SpC) to show that corticospinal (CS) synapses, once present throughout the SpC, are eliminated from the ventral side during development in an NMDAR-dependent manner.

Regionally specific distribution of corticospinal synapses because of activity-dependent synapse elimination in vitro.

We have shown previously that the corticospinal tract (CST) with functional connections can be reconstructed in vitro in slice cocultures. Using that system, we stimulated the deep cortical layer and recorded field EPSPs (fEPSPs) along a 100 microm-interval lattice in the spinal gray matter. The specific, spatial synapse distribution on the dorsal side at 14 d in vitro (DIV) basically corresponded to the in vivo area in which CST axons terminate.