Nerve Injury Induces Gap Junctional Coupling among Axotomized Adult Motor Neurons

Abstract

Neonatal spinal motor neurons are electrically and dye-coupled by gap junctions, but coupling is transient and disappears rapidly after birth. Here we report that adult motor neurons become recoupled by gap junctions after peripheral nerve injury. One and 4-6 weeks after nerve cut, clusters of dyecoupled motor neurons were observed among axotomized, but not control, lumbar spinal motor neurons in adult cats. Electrical coupling was not apparent, probably because of the electrotonic distance between dendrodendritic gap junctions and the somatic recording location. Analyses of gap junction protein expression in cat and rat showed that the repertoire of connexins expressed by normal adult motor neurons, Cx36, Cx37, Cx40, Cx43, and Cx45, was unchanged after axotomy. Our results suggest that the reestablishment of gap junctional coupling among axotomized adult motor neurons may occur by modulation of existing gap junction proteins that are constitutively expressed by motor neurons. After injury, interneuronal gap junctional coupling may mediate signaling that maintains the viability of axotomized motor neurons until synaptic connections are reestablished within their targets.

Transient Electrical Coupling Delays the Onset of Chemical Neurotransmission at Developing Synapses

“…However, in some invertebrates, like the crayfish, a "chemical-like" synapse has been shown to precede and give way to formation of an electrical synapse (Leitch et al, 1989). In vertebrates, expression of specific connexins decreases early in development (Rorig and Sutor, 1996;Chang et al, 1999Chang et al, , 2000Nadarajah and Parnavelas, 1999) at the onset of chemical synaptogenesis (Kandler and Katz, 1998). In many cases, the formation of the two types of synaptic connectivity is precisely timed, and they do not appear to coexist for long (for review, see Leitch, 1992).…”

Regulation of Motoneuron Excitability via Motor Endplate Acetylcholine Receptor Activation

“…The same signaling mechanism may also play an important role in driving events during reinnervation when reactivation of AChRs would presumably initiate the recovery of adult motoneuron properties. In conjunction with the elimination of any gap-junction coupling between motoneurons (Chang et al, 1999), this could help establish desynchronized motoneuron firing patterns (Binder and Powers, 2001) and drive synapse elimination, which otherwise would be inhibited by synchronous motoneuron firing (Busetto et al, 2000).…”

A Central Role of Connexin 43 in Hypoxic Preconditioning

“…Previous work has documented that cellular injury is linked to an upregulation of Cx43 expression in a variety of cells and tissues (Daleau et al, 2001;VanSlyke and Musil, 2005). For example, alveolar epithelial cells increased Cx43 expression after radiation (Kasper et al, 1996), smooth muscle cells exhibited increased Cx43 levels after balloon catheter injury of rat carotid artery (Yeh et al, 1997), multiple Cxs were upregulated after peripheral nerve injury (Chandross, 1998;Chang et al, 2000;Lin et al, 2002), and one of the earliest responses to kidney damage is an increase of Cx43 expression (Yaoita et al, 2002). Similarly, Cx43 is upregulated after spinal cord injury (Theriault et al, 1997;Lee et al, 2005) and in cortical astrocytes exposed to ischemia (Cotrina et al, 1998a;Lin et al, 2003).…”