Manipulation of BDNF Signaling Modifies the Experience-Dependent Plasticity Induced by Pure Tone Exposure during the Critical Period in the Primary Auditory Cortex

Bernd Sokolowski,Rogerio Panizzutti,Michael M Merzenich,Renata Anomal,Etienne De Villers-Sidani

doi:10.1371/journal.pone.0064208

Abstract

Sensory experience powerfully shapes cortical sensory representations during an early developmental “critical period” of plasticity. In the rat primary auditory cortex (A1), the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF), which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.

Highlights

The critical period is an initial postnatal epoch of cortical development that is highly susceptible to the plasticity induced by environmental stimuli [1]
The critical period for experience-dependent plasticity in A1 is linked to the emergence of fine-tuned cortical responses to auditory inputs, with most of the receptive fields becoming tuned across this period of maturation to a single frequency [8]
We observed that our manipulations of cortical brainderived neurotrophic factor (BDNF) during the critical period were mirrored by alterations in the expression of GABAA receptor subunits

Summary

Introduction

The critical period is an initial postnatal epoch of cortical development that is highly susceptible to the plasticity induced by environmental stimuli [1]. The exposure of rats to pure tone during the critical period augments the representation of that stimulus in the primary auditory cortex (A1) [6], [7]. Studies have showed that neurotrophins control the onset and closure of critical period as well as the magnitude of experiencedependent plasticity in the primary visual cortex (V1). In V1 development in mice, exposure of visual cortex to BDNF accelerates emergent GABAergic inhibition, which results in an earlier critical period closure [1], [12]. The present study was designed to determine whether BDNF modulates experience-dependent plasticity induced by pure tone exposure across the critical period for spectral tuning in A1. At the end of that exposure period, we mapped the electrophysiological receptive field to determine, by reference to control age-matched rats, whether or not BDNF or BDNF blocking altered stimulus-induced critical-period changes in A1

Experimental Procedures

Results

Discussion