Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity.

Lucas Matt,Thomas Ott,Anne E Bausch,Marlies Knipper,Wibke Singer,Ulrike Zimmermann,Lukas Rüttiger,Hyun-Soon Geisler,Rama Panford-Walsh,Karin Rohbock,Marie Manthey,Nicolas I C Müller,Thomas Schimmang,Peter Ruth,Csaba Harasztosi,Philipp Eckert,Eckhard Friauf

doi:10.3389/fnmol.2018.00260

Abstract

Activity-dependent BDNF (brain-derived neurotrophic factor) expression is hypothesized to be a cue for the context-specificity of memory formation. So far, activity-dependent BDNF cannot be explicitly monitored independently of basal BDNF levels. We used the BLEV (BDNF-live-exon-visualization) reporter mouse to specifically detect activity-dependent usage of Bdnf exon-IV and -VI promoters through bi-cistronic co-expression of CFP and YFP, respectively. Enriching acoustic stimuli led to improved peripheral and central auditory brainstem responses, increased Schaffer collateral LTP, and enhanced performance in the Morris water maze. Within the brainstem, neuronal activity was increased and accompanied by a trend for higher expression levels of Bdnf exon-IV-CFP and exon-VI-YFP transcripts. In the hippocampus BDNF transcripts were clearly increased parallel to changes in parvalbumin expression and were localized to specific neurons and capillaries. Severe acoustic trauma, in contrast, elevated neither Bdnf transcript levels, nor auditory responses, parvalbumin or LTP. Together, this suggests that critical sensory input is essential for recruitment of activity-dependent auditory-specific BDNF expression that may shape network adaptation.

Highlights

Brain-derived neurotrophic factor (BDNF), identified in 1982 (Barde et al, 1982), is recognized as key modulator of synaptic plasticity during homeostatic readjustment processes and a master regulator of energy homeostasis
The present findings suggest that exposure to acoustic enrichment (80 dB sound pressure levels (SPL)) and mild acoustic trauma (100 dB SPL), conditions that increase sound sensitivity, hippocampal long-term potentiation (LTP), and learning appears to correlate with an elevation of Bdnf exon-IV-CFP and Bdnf exon-VI-YFP in the brainstem and hippocampus
Different levels of acoustic exposure induced persisting changes in sound-sensitivity that apparently correlated with changes of Bdnf exon-IV-CFP and VI-YFP levels in the brainstem and hippocampus

Summary

Introduction

Brain-derived neurotrophic factor (BDNF), identified in 1982 (Barde et al, 1982), is recognized as key modulator of synaptic plasticity during homeostatic readjustment processes and a master regulator of energy homeostasis (for review see: Bramham and Messaoudi, 2005; Rauskolb et al, 2010; Park and Poo, 2013; Marosi and Mattson, 2014; Nahmani and Turrigiano, 2014; Jeanneteau and Arango-Lievano, 2016; Mitre et al, 2017). Visualizing BDNF During Sound-Induced Plasticity we do not yet understand BDNF’s influence on circuit stabilization in the adult system or its function in platelets (Chacón-Fernández et al, 2016), capillary endothelial cells (Donovan et al, 2000), microglia, and astrocytes (Ferrini and De Koninck, 2013; Parkhurst et al, 2013) during homeostatic readjustment processes (Nahmani and Turrigiano, 2014) Among other reasons, this is due to the difficulty of detecting the very low (Dieni et al, 2012) endogenous expression of BDNF in the mature central nervous system (CNS) (Dieni et al, 2012). BDNF was previously hypothesized to provide the corresponding signal (Jeanneteau and Arango-Lievano, 2016)

Methods

Results

Conclusion