Neuromuscular junctions (NMJs) innervated by motor neurons below spinal cord injury (SCI) have been reported to remain intact despite the interruption of supraspinal pathways and the resultant loss of activity. Here we report notably heterogeneous NMJ responses to SCI that include overt synapse disassembly. Complete transection of the thoracic spinal cord of adult rats evoked massive sprouting of nerve terminals in a subset of NMJs in ankle flexors, extensor digitorum longus, and tibialis anterior. Many of these synapses were extensively disassembled 2 weeks after spinal transection but by 2 months had reestablished synaptic organization despite continuous sprouting of their nerve terminals. In contrast, uniform and persistent loss of acetylcholine receptors (AChRs) was evident in another subset of NMJs in the same flexors, which apparently lacked terminal sprouting and largely maintained terminal arbors. Other synapses in the flexors, and almost all the synapses in the ankle extensors, medial gastrocnemius, and soleus, remained intact, with little pre- or postsynaptic alteration. Additional deafferentation of the transected animals did not alter the incidence or regional distribution of either type of the unstable synapses, whereas cycling exercise diminished their incidence. The muscle- and synapse-specific responses of NMJs therefore reflected differential sensitivity of the NMJs to inactivity rather than to differences in residual activity. These observations demonstrate the existence of multiple subpopulations of NMJs that differ distinctly in pre- and postsynaptic vulnerability to the loss of activity and highlight the anatomical instability of NMJs caudal to SCI, which may influence motor deficit and recovery after SCI.

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.