Experience‐dependent regulation of TrkB isoforms in rodent visual cortex

Abstract

Within primary visual cortex (V1), brain-derived neurotrophic factor (BDNF) signaling through its high-affinity receptor TrkB is important for normal development and experience-dependent plasticity. TrkB is expressed in several alternatively spliced isoforms, including full-length TrkB (TrkB.FL), and several truncated isoforms (TrkB.T1, TrkB.T2, and TrkB.T4) that lack the intracellular tyrosine kinase domain. These isoforms are important components of BDNF signaling, yet little is known about the developmental or experience-dependent regulation of their expression. Using immunohistochemistry, we found TrkB.FL and TrkB.T1 expressed in interneurons and pyramidal neurons within V1, but not in cortical astrocytes. We used real-time PCR to quantify the changes in mRNA expression of BDNF, the four TrkB isoforms, and the low-affinity receptor P75 NTR during normal development, and in response to visual deprivation at two different ages. BDNF expression increased between postnatal days 10 (P10) and P30, and was rapidly downregulated by 3 days of visual deprivation during both the pre-critical period (P14-P17) and the critical period (P18-P21). Over the same developmental period, expression of each TrkB isoform was regulated independently; TrkB.T1 increased, TrkB.FL and TrkB.T2 decreased, and TrkB.T4 showed transient changes. Neither brief visual deprivation nor prolonged dark-rearing induced changes in either TrkB.FL or TrkB.T1 expression. However, TrkB.T4 expression was reduced by brief visual deprivation, whereas TrkB.T4, TrkB.T2 and P75 NTR were up-regulated by prolonged dark-rearing into the critical period. Our data indicate that TrkB isoform expression can be selectively regulated by visual experience, and may contribute to experience-dependent cortical plasticity. '

Effects of chronic iTBS‐rTMS and enriched environment on visual cortex early critical period and visual pattern discrimination in dark‐reared rats

“…Visual experience after DR normalized the expression of these proteins. Our findings are in accordance with those of previous studies, showing reduced visual acuity after DR during the critical period (Fagiolini et al, ; Prusky et al, ) accompanied by reduced BDNF expression within the visual cortex of rats (Bracken and Turrigiano, ), and that environmental enrichment during DR has a compensatory effect (Pham et al, ; Cancedda et al, ; Sale et al, ). It has been further shown that high‐frequency rTMS applied to conscious rats is able to raise cortical BDNF levels in adult rats (Gersner et al, ).…”

Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain

“…Nevertheless, a growing list of CNS molecules are emerging as substrates for MMPs, such as β-dystroglycan, zona occludens-1, and myelin basic protein (13). A selective increase or decrease in cell surface presentation of truncated receptors, internalization of ligand-bound receptors, and stimulus-dependent TRKB processing by agents such as zinc are some known pathways through which BDNF is trapped, salvaged, or scavenged (14,15). Such mechanisms may predominate in situations requiring a rapid and reversible alteration of TRKB on neurons.…”

TrkB and Protein Kinase M ζ Regulate Synaptic Localization of PSD-95 in Developing Cortex

“…Evidence for BDNF/TrkB functions in pyramidal neurons (Bracken and Turrigiano, 2009) and their developing spines is also abundant (Tyler and Pozzo-Miller, 2003; Chakravarthy et al, 2006; Tanaka et al, 2008). Furthermore, it has been established that PSD-95 at synapses is crucial to spine maturation (Kim and Sheng, 2004; van Zundert et al, 2004) and that BDNF-TrkB signaling plays a central role in facilitating glutamate synapse stabilization/maturation through the PSD-95 scaffold (Ji et al, 2005; Yoshii and Constantine-Paton, 2007, 2010).…”