Amygdala hyperactivity and tonotopic shift after salicylate exposure

Abstract

The amygdala, important in forming and storing memories of aversive events, is believed to play a major role in debilitating tinnitus and hyperacusis. To explore this hypothesis, we recorded from the lateral amygdala (LA) and auditory cortex (AC) before and after treating rats with a dose of salicylate that induces tinnitus and hyperacusis-like behavior. Salicylate unexpectedly increased the amplitude of the local field potential (LFP) in the LA making it hyperactive to sounds ≥60 dB SPL. Frequency receptive fields (FRF) of multiunit (MU) clusters in the LA were also dramatically altered by salicylate. Neuronal activity at frequencies below 10 kHz and above 20 kHz was depressed at low intensities, but was greatly enhanced for stimuli between 10 and 20 kHz (frequencies near the pitch of the salicylate-induced tinnitus in the rat). These frequency-dependent changes caused the FRF of many LA neurons to migrate towards 10-20 kHz thereby amplifying activity from this region. To determine if salicylate-induced changes restricted to the LA would remotely affect neural activity in the AC, we used a micropipette to infuse salicylate (20 µl, 2.8 mM) into the amygdala. Local delivery of salicylate to the amygdala significantly increased the amplitude of the LFP recorded in the AC and selectively enhanced the neuronal activity of AC neurons at the mid-frequencies (10-20 kHz), frequencies associated with the tinnitus pitch. Taken together, these results indicate that systemic salicylate treatment can induce hyperactivity and tonotopic shift in the amygdala and infusion of salicylate into the amygdala can profoundly enhance sound-evoked activity in AC, changes likely to increase the perception and emotional salience of tinnitus and loud sounds.

Salicylate-induced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus

“…We tested this hypothesis by recording LFP I/O functions and multiunit discharge patterns in the LA before and after SS treatment (300 mg/kg, i.p.) as recently reported (Chen et al, 2012). Two hours after systemic SS treatment, the LFPs in the LA elicited by noise bursts were depressed at low intensities as recently noted (Figure 9A) (Chen et al, 2012).…”

“…as recently reported (Chen et al, 2012). Two hours after systemic SS treatment, the LFPs in the LA elicited by noise bursts were depressed at low intensities as recently noted (Figure 9A) (Chen et al, 2012). SS treatment elevated LA response thresholds approximately 20 dB similar to the shifts seen in the cochlea, MGB and AC.…”

“…The amplitude of the AC LFP increased substantially after local SS treatment (Figure 11A). However, the threshold of the LFP was unaffected (Figure 11B) as reported in our recent publication (Chen et al, 2012). These results suggest that the threshold elevation associated with systemic SS treatment originates in the cochlea whereas the suprathreshold hyperactivity arises in the CNS.…”

“…Neurons in the LA respond to acoustic stimuli and are sharply tuned (Figure 9B) as we and others have noted (Bordi et al, 1992; Chen et al, 2012). The frequency receptive field (FRF) of the LA multiunit cluster shown in Figure 9B originally had a CF near 2 kHz, a CF-threshold around 20 dB SPL and responded well to stimuli below 6 kHz.…”

“…To test this hypothesis, recordings were obtained from the AC before and after infusing SS (2.8 mM, 20 μl) into the ipsilateral LA as recently noted (Chen et al, 2012). Two hours after infusing SS into the LA, the amplitude of the AC LFP was greatly enhanced to noise bursts presented at suprathreshold intensities, but the response threshold was not shifted as illustrated in Figure 12A.…”