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      Auditory deprivation modifies the expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the rat auditory cortex

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          Abstract

          The development and plasticity of central auditory system can be influenced by the change of peripheral neuronal activity. However, the molecular mechanism participating in the process remains elusive. Brain-derived neurotrophic factor (BDNF) binding with its functional receptor tropomyosin receptor kinase B (TrkB) has multiple effects on neurons. Here we used a rat model of auditory deprivation by bilateral cochlear ablation, to investigate the changes in expression of BDNF and TrkB in the auditory cortex after auditory deprivation that occurred during the critical period for the development of central auditory system. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry methods were adopted to detect the mRNA and protein expression levels of BDNF and TrkB in the auditory cortex at 2, 4, 6 and 8 weeks after surgery, respectively. The change in the expression of BDNF and TrkB mRNAs and proteins followed similar trend. In the bilateral cochlear ablation groups, the BDNF-TrkB expression level initially decreased at 2 weeks but increased at 4 weeks followed by the reduction at 6 and 8 weeks after cochlear removal, as compared to the age-matched sham control groups. In conclusion, the BDNF-TrkB signaling is involved in the plasticity of auditory cortex in an activity-dependent manner.

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          Most cited references23

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          BDNF and activity-dependent synaptic modulation.

          Bai Lu (2003)
          It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapse-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner.
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            Critical period window for spectral tuning defined in the primary auditory cortex (A1) in the rat.

            Experience-dependent plasticity during development results in the emergence of highly adapted representations of the external world in the adult brain. Previous studies have convincingly shown that the primary auditory cortex (A1) of the rat possesses a postnatal period of sensory input-driven plasticity but its precise timing (onset, duration, end) has not been defined. In the present study, we examined the effects of pure-tone exposure on the auditory cortex of developing rat pups at different postnatal ages with a high temporal resolution. We found that pure-tone exposure resulted in profound, persistent alterations in sound representations in A1 only if the exposure occurred during a brief period extending from postnatal day 11 (P11) to P13. We also found that postnatal sound exposure in this epoch led to striking alterations in the cortical representation of sound intensity.
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              Activity-dependent modulation of the BDNF receptor TrkB: mechanisms and implications.

              Although brain-derived neurotrophic factor (BDNF) has emerged as a key regulator of activity-dependent synaptic plasticity, a conceptually challenging question is how this diffusible molecule achieves local and synapse-specific modulation. One hypothesis is that neuronal activity enhances BDNF signaling by selectively modulating TrkB receptors at active neurons or synapses without affecting receptors on neighboring, less-active ones. Growing evidence suggests that neuronal activity facilitates cell-surface expression of TrkB. BDNF secreted from active synapses and neurons recruits TrkB from extrasynaptic sites into lipid rafts, microdomains of membrane that are enriched at synapses. Postsynaptic rises in cAMP concentrations facilitate translocation of TrkB into the postsynaptic density. Finally, neuronal activity promotes BDNF-induced TrkB endocytosis, a signaling event important for many long-term BDNF functions. These mechanisms could collectively underlie synapse-specific regulation by BDNF.
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                Author and article information

                Contributors
                Journal
                J Otol
                J Otol
                Journal of Otology
                Chinese PLA General Hospital
                1672-2930
                08 March 2017
                March 2017
                08 March 2017
                : 12
                : 1
                : 34-40
                Affiliations
                [a ]Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China
                [b ]Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China
                Author notes
                []Corresponding author. Fax: +86 31166002736. wx_900804@ 123456163.com
                Article
                S1672-2930(16)30084-8
                10.1016/j.joto.2017.02.003
                6011803
                dddcc6e7-6393-4bfe-b319-7d2f14de8723
                Copyright © 2017, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 November 2016
                : 16 February 2017
                : 20 February 2017
                Categories
                Research Article

                central plasticity,brain-derived neurotrophic factor,tropomyosin receptor kinase b,auditory deprivation,auditory cortex

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