TY  - JOUR
A1  - Chumak, Tetyana
A1  - Rüttiger, Lukas
A1  - Lee, Sze Chim
A1  - Campanelli, Dario
A1  - Zuccotti, Annalisa
A1  - Singer, Wibke
A1  - Popelář, Jiří
A1  - Gutsche, Katja
A1  - Geisler, Hyun-Soon
A1  - Schraven, Sebastian Philipp
A1  - Jaumann, Mirko
A1  - Panford-Walsh, Rama
A1  - Hu, Jing
A1  - Schimmang, Thomas
A1  - Zimmermann, Ulrike
A1  - Syka, Josef
A1  - Knipper, Marlies
T1  - BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury
JF  - Molecular Neurobiology
N2  - For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF \(^{Pax2}\) -KO) versus the auditory cortex and hippocampus (BDNF \(^{TrkC}\) -KO). We demonstrate that BDNF \(^{Pax2}\) -KO but not BDNF \(^{TrkC}\) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF \(^{Pax2}\) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF \(^{Pax2}\) -KO, but not of BDNF \(^{TrkC}\) -KO mice. Also, BDNF \(^{Pax2}\) -WT but not BDNF \(^{Pax2}\) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise.
KW  - Inner hair cell
KW  - Neurotropathic Factor
KW  - Hearing-loss
KW  - Alzheimers-disease
KW  - low-threshold fibers
KW  - cochlear nucleus neurons
KW  - Frequency-response areas
KW  - Inferior colliculus
KW  - Environmental enrichment
KW  - Synaptic plasticity
KW  - Cortical plasticity
KW  - BDNF
KW  - Central hyperactivity
KW  - High-spontaneous rate
KW  - Homeostatic plasticity
KW  - Sound detection threshold
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187341
VL  - 53
IS  - 8
ER  - 
TY  - JOUR
A1  - Asthana, Manish Kumar
A1  - Brunhuber, Bettina
A1  - Mühlberger, Andreas
A1  - Reif, Andreas
A1  - Schneider, Simone
A1  - Herrmann, Martin J.
T1  - Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism
JF  - International Journal of Neuropsychopharmacology
N2  - Background:

Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans.

Methods:

An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265.

Results:

The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation.

Conclusions:

Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans.
KW  - BDNF
KW  - brain derived neurotrophic factor
KW  - fear conditioning
KW  - genetics memory
KW  - reconsolidation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166217
VL  - 19
IS  - 6
ER  -