Developmental hearing loss eliminates long-term potentiation in the auditory cortex

Abstract

Severe hearing loss during early development is associated with deficits in speech and language acquisition. Although functional studies have shown a deafness-induced alteration of synaptic strength, it is not known whether long-term synaptic plasticity depends on auditory experience. In this study, sensorineural hearing loss (SNHL) was induced surgically in developing gerbils at postnatal day 10, and excitatory synaptic plasticity was examined subsequently in a brain slice preparation that preserves the thalamorecipient auditory cortex. Extracellular stimuli were applied at layer 6 (L6), whereas evoked excitatory synaptic potentials (EPSPs) were recorded from L5 neurons by using a whole-cell current clamp configuration. In control neurons, the conditioning stimulation of L6 significantly altered EPSP amplitude for at least 1 h. Approximately half of neurons displayed long-term potentiation (LTP), whereas the other half displayed long-term depression (LTD). In contrast, SNHL neurons displayed only LTD after the conditioning stimulation of L6. Finally, the vast majority of neurons recorded from control prehearing animals (postnatal days 9-11) displayed LTD after L6 stimulation. Thus, normal auditory experience may be essential for the maturation of synaptic plasticity mechanisms.

Fig. 1.

LTP was induced in a control posthearing L5 auditory cortex pyramidal neuron. (A) A 50-pA suprathreshold current pulse was injected to characterize the firing pattern. (B) An example of L6-evoked EPSPs at increasing stimulus intensities. For induction of synaptic plasticity, the stimulus intensity was chosen to produce a 50% amplitude EPSP. This strategy allowed normalization of EPSP amplitude to create a window for synaptic potentiation or depression by the subsequently conditioning stimuli applied at the same site (L6). (C) An EPSP trace recorded at the beginning of the experiment (Preconditioning) (Left) and an enhanced EPSP trace (Right) 1 h after the conditioning protocol. (Center) The neuron's response to one of several bursts within a conditioning stimulus is shown.

Fig. 2.

LTD was induced in a control posthearing L5 ACx pyramidal neuron. (A) A 90-pA suprathreshold depolarizing current pulse was injected to characterize the firing pattern (regular spiking). (B) An EPSP trace recorded at the beginning of the experiment (Preconditioning) (Left) and a significantly depressed EPSP trace (Right) 1 h after the conditioning protocol. (Center) The neuron's response to one of several bursts within a conditioning stimulus is shown.

Fig. 3.

Examples of bidirectional plasticity in L5 neurons. Baseline EPSPs were acquired for 10 min before the conditioning stimulus (gray bars). EPSPs were then acquired for an additional hour. (A) Expression of LTP in a control posthearing neuron. (B) Relatively weak LTP in a prehearing neuron. (C) Expression of LTD in a control posthearing neuron. (D) LTD in a prehearing neuron. (E) LTD in a SNHL neuron. The plasticity induction protocol was similar for all cases. Postnatal age is in parentheses.

Fig. 4.

Expression of either LTP or LTD for all control posthearing neurons. Baseline EPSPs were acquired for 10 min before the conditioning stimulus (gray bar). EPSPs were then acquired for an additional hour. (A) Approximately half of the neurons displayed LTP (filled symbols). (B) Approximately half of the neurons displayed LTD (open symbols) (mean EPSP amplitude ± SEM).

Fig. 5.

Difference in the magnitude of control LTP versus LTD. Percent change in the amplitude of the last three EPSPs after the conditioning stimulus were compared with the mean of first three EPSPs for all control posthearing neurons. This analysis showed the minimum change in synaptic strength in an individual neuron (LTP or LTD) was 26% for LTP (mean = 79%) and 27% for LTD (mean = 47%). Thus, the control population did not display a single-peaked distribution.

Fig. 6.

Hearing loss eliminates LTP. Baseline EPSPs were acquired for 10 min before the conditioning stimulus (gray bar). EPSPs were then acquired for an additional hour. (A) An EPSP trace recorded from an SNHL neuron at the beginning of the experiment (Preconditioning) (Left) and a significantly depressed EPSP trace (Right) obtained 1 h after the conditioning protocol. (Center) The neuron's response to one of several bursts within a conditioning stimulus is shown. (B) Control LTD (open circles) data are plotted for comparison (mean EPSP amplitude ± SEM). See Results for statistics.

Fig. 7.

LTD is prominent in prehearing animals. (A) An EPSP trace recorded from a prehearing animal at the beginning of the experiment (Preconditioning) (Left) and a significantly depressed EPSP trace (Right) obtained 1 h after the conditioning protocol. (Center) The neuron's response to one of several bursts within a train is shown. (B) Baseline EPSPs were acquired for 10 min before the conditioning protocol (gray bar). EPSPs were then acquired for an additional hour. Control LTD (open circles) data are plotted for comparison (mean EPSP amplitude ± SEM). (C) The bar graph displays the incidence of LTP and LTD in pre- versus posthearing neurons. Note the bias toward LTD in prehearing neurons.

Fig. 8.

Dendritic morphology does not correspond with the direction of plasticity. The photomicrographs show two biocytin-labeled IB neurons, each recorded in L5 ACx of a control posthearing animal. The neuron on the left displayed LTD, whereas the neuron on the right displayed LTD.