Transient Hearing Loss Within a Critical Period Causes Persistent Changes to Cellular Properties in Adult Auditory Cortex

Abstract

Sensory deprivation can induce profound changes to central processing during developmental critical periods (CPs), and the recovery of normal function is maximal if the sensory input is restored during these epochs. Therefore, we asked whether mild and transient hearing loss (HL) during discrete CPs could induce changes to cortical cellular physiology. Electrical and inhibitory synaptic properties were obtained from auditory cortex pyramidal neurons using whole-cell recordings after bilateral earplug insertion or following earplug removal. Varying the age of HL onset revealed brief CPs of vulnerability for membrane and firing properties, as well as, inhibitory synaptic currents. These CPs closed 1 week after ear canal opening on postnatal day (P) 18. To examine whether the cellular properties could recover from HL, earplugs were removed prior to (P17) or after (P23), the closure of these CPs. The earlier age of hearing restoration led to greater recovery of cellular function, but firing rate remained disrupted. When earplugs were removed after the closure of these CPs, several changes persisted into adulthood. Therefore, long-lasting cellular deficits that emerge from transient deprivation during a CP may contribute to delayed acquisition of auditory skills in children who experience temporary HL.

Keywords: auditory; hearing loss; intrinsic property; recovery; sensitive period.

Figure 1.

Thalamocortical slice preparation and auditory thresholds. (A) Diagrammatic sketch illustrates the thalamocortical slice preparation and L2/3 sampling region where whole-cell recordings were conducted (gray area). MGN: medial geniculate nucleus, LGN: lateral geniculate nucleus, Hipp: Hippocampus, and ACx: primary auditory cortex. (B) Line plot shows behaviorally assessed auditory thresholds for control animals (gray bar; n = 3) and animals that received earplugs on P11 (red bar; n = 3). Dashed line represents a threshold criterion of d′ = 1. (C) Bar graph shows the group average and individual auditory threshold for control animals, and earplug animals before and after earplug removal. * = P < 0.05.

Figure 2.

Membrane properties display a CP for EP onset between P11 and P13. (A) A schematic illustrating experimental design to investigate the age of hearing loss onset. (B) Representative example traces of the effect of earplugging between P11 and P23 on membrane properties in response to depolarizing current injection 50 pA above firing threshold or hyperpolarizing current injection −30 pA from resting potential. (C–H) Bar graphs showing the CP for action potential amplitude, action potential HW, RMP, input resistance, membrane time constant, and action potential threshold. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 3.

Specific membrane properties display a CP for EP onset for both P11 to P13 and P14 to P17. (A) A schematic illustrating experimental design to investigate the age of hearing loss onset. (B) Top, representative example traces of the effect of EP between P11 and P23 on the membrane response to hyperpolarizing current injection of −100 pA/1500 ms. Bottom, bar graph shows the 2 CPs of development for depolarizing sag emanating after peak hyperpolarization. (C) Top, Representative traces of the effect of earplugging between P11 and P23 on the response to depolarizing current injection between resting potential and action potential threshold. Bottom, bar graph shows the 2 CPs of development for membrane depolarization in response to a +10 pA current step. (D) Top, representative traces of current-evoked discharge in response to depolarizing current injection of 600 pA. Bottom, Line plots displaying the impact of earplugging from P11 to P13 (red) and P14 to P17 (blue) on firing rates (left), and the impact of earplugging between P18 and P23 on firing rates (right). *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 4.

CP for the influence of EP onset on the development of inhibitory synaptic transmission. (A) Effect of earplugging on spontaneous IPSC amplitude and decay time constant. Left: representative recordings of sIPSC amplitudes. Individual sIPSC displays decay time constant. Right; bar graph showing the quantitative effect of earplugging on sIPSC amplitudes and decay time constant. (B) Effect of earplugging on intracortically-evoked minimum IPSC amplitude. Left: representative example recordings of me-IPSCs. Right: bar graph showing the quantitative effect of earplugging on me-IPSC amplitudes. All recordings were carried out in the presence of DNQX and AP-5. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 5.

The impact of auditory deprivation duration on membrane property development. Line plots display the normal development (black) and effect of EP duration (red) for (A) input resistance, (B) time constant, (C) ΔmV, (D) action potential threshold, (E) action potential amplitude, (F) action potential HW, (G) RMP, (H) depolarizing sag, (I, J) firing rate. Dashed rectangles highlight properties that remain significantly different at P29-35. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 6.

The CP for recovery of membrane and firing properties following EP removal. (A) A schematic illustrates the experimental design used to investigate recovery from hearing loss. (B–F) Bar graphs showing the effect of P11 earplugging on action potential amplitude, RMP, action potential HW, depolarizing sag, and ΔmV when earplugs are removed on P17 followed by short-term recovery (P23), earplug removal at P23 followed by short-term recovery (P35), or earplug removal at P23 followed by long-term recovery (P86). (G–I) Line plots displaying the impact of P11 earplugging on firing rates when earplugs are removed at P17 followed by short-term recovery (P23), earplug removal at P23 followed by short-term recovery (P35), or earplug removal at P23 followed by long-term recovery (P86). *P < 0.05, **P < 0.01, ***P < 0.001.