Visualizing BDNF Transcript Usage During Sound-Induced Memory Linked Plasticity

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.

Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF

“…We also observed that central auditory compensation after acoustic trauma-induced cochlear deafferentation was linked to increased hippocampal long-term potentiation (LTP), and recruitment of activity-dependent Bdnf exon-IV and -VI transcription [ 24 ], providing a mechanistic explanation for the idea that temporal auditory processing abilities are related to each individual’s cognitive skills [ 25 ].…”

Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor

“…Thus, we conclude that a decrease in BNDF levels in the hippocampus of rats submitted to one minute of high-intensity sound, impairs the expression of LTP in the Schaffer-CA1 synapse. Interestingly, Matt et al, (2018) found that prolonged exposure to traumatic noise (120 dB, 6 hours per day for 21 days) in anesthetized rats did not alter LTP and BDNF expression. This suggests that the anesthesia or the prolonged sound exposure protocol might change the hippocampal response to high-intensity sound.…”

“…On the other hand, daily exposure to music at moderated intensity levels (60 dB, 6 hours per day for 21 days) enhanced learning performance and increased BDNF expression in the hippocampus (Angelucci et al, 2007). Similarly, exposure to an 80 dB sound at 10 kHz for 40 minutes in anesthetized rats, increased BDNF expression, hippocampal LTP magnitude and improved the performance in the Morris water maze (Matt et al, 2018). It appears that the effect of moderate noise is more related to the type of noise, and it seems to be contradictory depending on the reports.…”

“…Additionally, exposure to moderate to loud sounds can lead to impairment of spatial and associative memory, which seems to be associated to an oxidative status imbalance (Uran et al, 2010(Uran et al, , 2012Manikandan et al, 2016). On the other hand, 40minutes exposure to mild (80dB) sounds, potentiated hippocampal long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) expression (Matt et al, 2018). Finally, we have shown that one minute exposure to a high-intensity (110-120 dB) broadband sound inhibits LTP in the Schaffer-CA1 synapses in the hippocampus of rats for 24 hours after exposure (de Deus et al, 2017), an effect not related to corticosterone secretion, and not observed after moderate noise (80 dB) exposure.…”

Impacto da estimulação sonora de alta intensidade na plasticidade sináptica de longo prazo e na neurotransmissão hipocampal

“…A aplicação de BDNF em fatias de hipocampo recupera a LTP em fatias de ratos submetidos à hipóxia crônica intermitente, que apresentam um déficit da LTP hipocampal (Xie et al, 2010). Além disso, em animais transfectados para expressão de BDNF com a sequência exon IV e VI e co-expressão fluorescente de CFP e YFP, foi observado que o enriquecimento acústico com 80 dB melhora as respostas auditivas no tronco encefálico, causa potenciação da LTP nas colaterais de Schaffer, melhora o desempenho dos animais no LAM e aumenta a transcrição de BDNF, ao passo que animais submetidos ao trauma acústico de 120 dB não apresentam aumento na transcrição de BDNF e potenciação da LTP, e apresentam piora no desempenho no LAM (Matt et al, 2018).…”