Manipulation of BDNF signaling modifies the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex

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.

Figure 1. Manipulation of BDNF signaling during critical period affects the tonotopic organization, receptive fields and cortical representation of A1.

(A, B, C) Tonotopic maps (left) of control, anti-BDNF, and BDNF groups; x = no tone-evoke responses; circle inside polygon = multi/flat-peaked sites. (Center) Distributions of tuning curves from illustrated map. The pair of joined lines represents the receptive field of each recorded site, and the apex indicates the threshold of activation of these sites. (Right) Representative receptive field from each displayed map (see number inside maps). (D) Receptive fields tuned to 7 kHz±0.3 octave were significantly increased in the BDNF group compared to control and anti-BDNF groups (F = 7.3, p<0.05, ANOVA). (E, F) The proportion of receptive fields tuned to frequencies higher than 7 kHz±0.3 octave (A) or lower than 7 kHz±0.3 octave (B) were not significantly different between groups. Values are means ± SEM. * p<0.05. Calibration bar = 1 mm.

Figure 2. Manipulation of BDNF signaling affects spectral selectivity.

(A) Percentage of single and multi/flat-peaked receptive fields for each study group. The percentage of single-peaked receptive fields was significantly reduced in the anti-BDNF group compared to controls (F = 13.6, p = 0.003, ANOVA). (B) Response bandwidths above threshold (BW20) were significantly augmented in the anti-BDNF group compared to controls (F = 7.3, p = 0.007, ANOVA). Values are means ± SEM. * p<0.05.

Figure 3. Manipulation of BDNF signaling affects the expression of GABA receptors in A1.

Expression of GABA_A β2/3 subunits measured using quantitative immunoblotting in the different rat groups (3 animals per group). The insert shows a representative western blot. Values are means ± SEM. * significantly different than control rats at p<0.01.