Abstract
The p75 neurotrophin receptor, which binds to all neurotrophins, is implicated in apoptosis, survival, neurite outgrowth, synaptic transmission, and myelination (Dechant & Barde 2002). Upon BDNF treatment, sympathetic neurons co-cultured with cardiac myocytes undergo a rapid p75- mediated switch from an excitatory noradrenergic to inhibitory cholinergic phenotype (Yang et al. 2002). The present in vivo study indicates that adult p75 KOs may have hyperinnervated atria. In aged mice, the apparent hyperinnervation could not be attributed to increased sympathetic fibers. However, cardiac sympathetic innervation in p75 KOs may develop at an accelerated pace. Also, p75 appears to be important in early postnatal patterning of atrial innervation. A hypothesized mechanism for the p75-mediated switch in neurotransmitter phenotypes of cultured sympathetic neurons (Yang et al. 2002) is that synapsin I phosphorylation leads to untethering of cytoskeleton-bound vesicles. This possibility was tested in vitro. Although high variability precludes conclusions, the trend suggests that neurotrophic factor treatment lowers the ratio of synapsin I puncta staining relative to SV2 puncta staining in sympathetic neurites. The lowered ratio appears to reflect slight increases in SV2 puncta staining rather than decreases in synapsin I puncta staining. We were also interested in understanding how the presence of non-neuronal targets such as cardiac myocytes may inhibit the development of functional connections between neurons. Using microarray teclmology, synapsin II has been identified for differential expression in conditions where neurons and myocytes are grown together or separately (Moon & Birren, unpublished). More experiments need to be done, but preliminary immunocytochemistry data suggests that the presence of myocytes may lead to de-aggregation of synapsin II on certain portions of sympathetic neurites.