Effects of dark rearing on phosphorylation of neurotrophin Trk receptors

Abstract

Total lack of visual experience (dark rearing, DR) is known to affect development of mammalian visual cortex (VC) and to prolong the critical period of visual cortical plasticity. Neurotrophins (NTs) have been proposed to play a relevant role in activity dependent processes important for the final shaping of cortical visual connections. Neurotrophin supply or antagonism of endogenous NT action profoundly affect visual cortical development and plasticity; in particular, exogenous supply of NTs counteracts DR effects on VC development. However, the effects of DR on NT expression are still debated and mounting evidence reports a mismatch between BDNF mRNA and protein expression in DR animals. To gain insight into the effects of DR on expression of nerve growth factor (NGF) and the functional state of NT signalling pathways, we assessed the phosphorylation state of Trk receptors in light-reared animals (LR), in dark-reared animals (DR), in DR animals briefly exposed to light and in DR animals with exogenous supply of NTs [NGF, brain-derived neurotrophic factor (BDNF) and NT-4] in the VC. We report that DR increases the expression of NGF but reduces the phosphorylation of TrkA and TrkB receptors with respect to LR; normal phosphorylation is rapidly rescued by a brief exposure to light. Exogenous supply of NGF, BDNF or NT4 in DR animals also rescues the phosphorylation of their receptors.

Brain-Derived Neurotrophic Factor and TrkB Modulate Visual Experience-Dependent Refinement of Neuronal Pathways in Retina

“…BDNF protein levels are reduced in the retinas of dark-reared animals or in retinas of lid-sutured eyes (Seki et al, 2003;Mandolesi et al, 2005; this study). TrkB protein expression in retina and visual cortex is not altered by dark rearing (Viegi et al, 2002). These previous findings together with our results support the idea that visual stimulation during postnatal development regulates the transcription and protein levels of BDNF in retina, and BDNF, acting at TrkB receptors, is an important signaling molecule modulating visual experiencedependent plasticity of RGCs.…”

Microglia Function in Central Nervous System Development and Plasticity

“…Interestingly, many of the spines contacted by microglia tended to be smaller and were often no longer present at later imaging sessions, data suggesting microglia may be playing a role in the elimination of these spines. To address how activity may be involved, the investigators also visualized microglia -synapse interactions following a dark adaptation paradigm known to elicit robust synaptic remodeling (Mower et al 1983;Philpot et al 2001;Viegi et al 2002;Tropea et al 2010). Using this paradigm, in dark-adapted mice or dark-adapted mice re-exposed to light, live imaging revealed that microglia changed their motility and interactions with spines as compared with lightreared control animals.…”

Transient Synaptic Silencing of Developing Striate Cortex Has Persistent Effects on Visual Function and Plasticity

“…Proteins were extracted (Viegi et al, 2002) with lysis buffer (1% Triton X-100, 10% glycerol, 20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 10 mM EDTA, 0.1 mM Na 3 VO 4 , 1 g/ml leupeptin, 1 g/ml aprotinin, and 1 mM PMSF). Protein extracts (10 g) were separated by electrophoresis and blotted, and filters were incubated with an antibody specific for the BoNT/E-cleaved form of SNAP-25 (1:50 dilution) or with an antibody recognizing both BoNT/Ecleaved and intact SNAP-25 (1:1000; Sternberger Monoclonals, Lutherville, MD).…”