Role of peripheral BDNF for auditory perceptional learning?

Abstract

[Background]: While novel studies indicate that perceptional learning is not linked with permanent changes in cortical circuitry but rather with changes that are gated in a task- or context-dependent fashion, the molecular substrate of perceptional learning is still elusive. It is currently speculated that perhaps changes in synaptic weights restricted to a limited set of task-specific synapses play a crucial role (Irvine DRF Hearing Res. 2018, Zhang Y-X et al. Amitay S 2016, Plos One). BDNF is gradually upregulated in the cochlea and ascending auditory pathway onwards from prior hearing onset (postnatal day P4) (Singer et al., Knipper, Neuropharmacol 2014). Previously, we showed that peripheral BDNF in the cochlea or lower brainstem regions, but not in the central higher cortical brain regions is fundamental for improved and optimized auditory fidelity with hearing onset [Zuccotti A et al. Knipper, 2012, J Neuroscience, Chumak T et al., 2016, Mol Neurobiol]. This improved auditory fidelity included greater sensitivity of auditory fibers, lower hearing thresholds, and enlarged dynamic range and inhibitory strength in the inferior colliculus related to lowering of spontaneous firing rate. We here asked to what extend these BDNF driven changes in auditory fidelity may influence memory-related shaping of auditory skills and auditory perceptional learning.

[Methods]: Using conditional BDNF Pax2 KO mice, lacking BDNF in the cochlea, DCN and IC, we compared auditory fine structure analysis, auditory steady state response (ASSR), LTP and LTP-dependent task performance in BDNF WT and mutant mice, and investigated changes in markers for excitatory and inhibitory neuronal activity using high-resolution confocal microscopy and quantitative westernblot approaches.

[Results]: Fundamental differences were found between BDNF Pax2 WT and KO mice at the molecular, functional, and behavioral level. The findings are discussed in the context of a role of BDNF for auditory perceptional learning in lower auditory brainstem regions.