Neural (N)-cadherin at developing thalamocortical synapses provides an adhesion mechanism for the formation of somatopically organized connections

Abstract

Thalamic projections from the ventrobasal (VB) nucleus to rodent somatosensory cortex develop highly ordered terminations that form discrete, clustered patches localized to layer IV cellular aggregates that are termed "barrels." The molecular signaling and adhesion events that occur at the synapse as barrel-clustered thalamic connections form are unknown. Here, we show that neural (N)-cadherin, a membrane glycoprotein mediating strong homophilic adhesion, is concentrated at the developing thalamocortical synaptic junctional complex and demarcates these synaptic junctions as they form their characteristic barrel clusters during the first postnatal week. Furthermore, experimentally altering the distribution of thalamocortical axon terminals by peripheral manipulation leads to an identically altered N-cadherin distribution pattern, which is significant in establishing that N-cadherin does not define region-specific patterns of synapse distribution proactively but, rather, conforms to patterning imposed by thalamic axons through instructional cues conveyed through several synaptic relays. At postnatal day 9, levels of N-cadherin expression rapidly decrease, leading to loss of N-cadherin labeling of the barrels and, at adulthood, elimination from VB thalamocortical synapses. However, alphaN- and beta-catenin, which are critical binding partners of the classic cadherins, persist at the adult synapse, suggesting the presence of another classic cadherin as the thalamocortical synapse matures. This is the first evidence linking a synapse adhesion molecule with the establishment of patterned thalamocortical synapse distribution, suggesting strongly that N-cadherin performs a critical role in this process by adhering presynaptic and postsynaptic membranes as ingrowing thalamic axon terminals and postsynaptic thalamorecipient sites link and stabilize into mature synaptic junctional complexes distributed with precise topographic order. It is speculated that the developmental redistribution of N-cadherin may reflect dynamic regulation of synaptic membrane adhesion, which, in turn, might modulate plasticity of thalamocortical synaptic function.