Long-Lasting forward Suppression of Spontaneous Firing in Auditory Neurons: Implication to the Residual Inhibition of Tinnitus

Abstract

Tinnitus is the perception of a sound that has no external source. Sound stimuli can suppress spontaneous firing in auditory neurons long after stimulus offset. It is unknown how changes in sound stimulus parameters affect this forward suppression. Using in vivo extracellular recording in awake mice, we found that about 40 % of spontaneously active inferior colliculus (IC) neurons exhibited forward suppression of spontaneous activity after sound offset. The duration of this suppression increased with sound duration and lasted about 40 s following a 30-s stimulus offset. Pure tones presented at the neuron's characteristic frequency (CF) were more effective in triggering suppression compared to non-CF or wideband noise stimuli. In contrast, non-CF stimuli often induced forward facilitation. About one third of IC neurons exhibited shorter suppression durations with each subsequent sound presentation. These characteristics of forward suppression are similar to the psychoacoustic properties of residual inhibition of tinnitus: a phenomenon of brief (about 30 s) suppression of tinnitus observed in tinnitus patients after sound presentations. Because elevated spontaneous firing in central auditory neurons has been linked to tinnitus, forward suppression of this firing with sound might be an underlying mechanism of residual inhibition.

Keywords: acoustic trauma; inferior colliculus; mice; residual inhibition.

FIG. 1

Long-lasting suppression of spontaneous firing in an IC neuron following a sound stimulus. PSTH of a single recording of an IC neuron in response to a pure tone (30-s duration) presented at the neuron’s CF (18 kHz) at 70 dB SPL or 40 dB above the neuron’s response threshold. Horizontal semitransparent bar represents an averaged level of spontaneous firing ±2 SD calculated based on spontaneous neuronal firing recorded during 5 s before the stimulus onset. The hashed bar indicates the duration of suppression (52 s, shown above). The sound stimulus is shown by a black horizontal bar below the histograms (same timescale as histogram). Bin size is 1 s.

FIG. 2

Suppression duration of spontaneous firing in an IC neuron increases with sound stimulus duration. PSTH of a single recording of an IC neuron in response to a pure tone of 5-s (a) and 30-s (b) duration presented at the neuron’s CF (16 kHz) at 65 dB SPL or 40 dB above the neuron’s response threshold. The duration of suppression was 6 s in a and 38 s in b. See legend of Figure 1 for other details.

FIG. 3

Duration of the suppression correlates with sound duration (r = 0.71, p < 0.0001). Suppression in 27 IC neurons was determined in response to both the 5-s and 30-s sound duration.

FIG. 4

Duration of suppression in IC neurons in response to a pure tone at the neurons’ CF is longer than in response to a wideband noise. a PSTH of a single recording of an IC neuron to a 30-s pure tone at neuron’s CF (24 kHz) presented at 65 dB SPL or 40 dB above threshold. b PSTH of the same neuron in response to a wideband noise. To compensate for the power loss, the wideband noise was presented 10 dB louder (75 dB SPL). The duration of suppression was 38 s in a and 17 s in b. See legend of Figure 1 for other details.

FIG. 5

A small subset of IC neurons exhibited firing rate suppression in response to the neuron’s CF yet with facilitation to non-CFs. a PSTH of a single recording of an IC neuron in response to a 30-s pure tone at neuron’s CF (14 kHz) presented at 75 dB SPL or 40 dB above the neuron’s threshold. b PSTH of the same neuron in response to a non-CF (18 kHz). There was 7-s duration of suppression in a and 9 s of facilitation in b. See legend of Figure 1 for other details.

FIG. 6

Duration of suppression decreased when a consecutive series of sound stimuli were presented. a PSTH of a single recording of an IC neuron to a 5-s pure tone at neuron’s CF (12 kHz) presented at 70 dB SPL or 40 dB above the neuron’s threshold. (b, c) PSTH of the same neuron in response to two more sound presentations. Note that duration of suppression decreased with each subsequent stimulus presentations (a 19 s, b 7 s, c 4 s). Bin size is 1 s. See legend of Figure 1 for other details.

FIG. 7

Facilitation of spontaneous firing in an IC neuron following sound-evoked suppression. PSTH of a single recording of an IC neuron in response to a 30-s pure tone presented at the neuron’s CF (12 kHz) at 60 dB SPL or 40 dB above the neuron’s response threshold. Black arrow indicates the facilitation. See legend of Figure 1 for other details.

FIG. 8

Suppression of spontaneous firing in IC neurons of tinnitus positive and naïve mice is similar. a PSTH of a single recording of an IC neuron in a tinnitus positive mouse to a 5-s pure tone presented at the neuron’s CF (25 kHz) at 70 dB SPL or 40 dB above the neuron’s response threshold. b Comparison of the duration of suppression to 5-s sound stimuli presented at neurons’ CF in IC neurons of the control and tinnitus positive mice. See legend of Figure 1 for other details.