Effects of sodium salicylate on spontaneous and evoked spike rate in the dorsal cochlear nucleus

Abstract

Spontaneous hyperactivity in the dorsal cochlear nucleus (DCN), particularly in fusiform cells, has been proposed as a neural generator of tinnitus. To determine if sodium salicylate, a reliable tinnitus inducer, could evoke hyperactivity in the DCN, we measured the spontaneous and depolarization-evoked spike rate in fusiform and cartwheel cells during salicylate superfusion. Five minute treatment with 1.4 mM salicylate suppressed spontaneous and evoked firing in fusiform cells; this decrease partially recovered after salicylate washout. Less suppression and greater recovery occurred with 3 min treatment using 1.4 mM salicylate. In contrast, salicylate had no effect on the spontaneous or evoked firing of cartwheel cells indicating that salicylate's suppressive effects are specific to fusiform cells. To determine if salicylate's suppressive effects were a consequence of increased synaptic inhibition, spontaneous inhibitory postsynaptic currents (IPSC) were measured during salicylate treatment. Salicylate unexpectedly reduced IPSC thereby ruling out increased inhibition as a mechanism to explain the depressed firing rates in fusiform cells. The salicylate-induced suppression of fusiform spike rate apparently arises from unidentified changes in the cell's intrinsic excitability.

Figure 1

Protocol for current clamp recording. During current clamp recording, cell injected with −126 pA except during acquisition of spontaneous and evoked spike rate when the current was 0 and +126 pA. A hyperpolarization current step was performed between two recording periods to monitor the input resistance. Salicylate was applied for 5 minutes starting at minute 5, followed by a wash out period.

Figure 2

A sample plot of spontaneous spike rate of fusiform cell obtained during 5-s intervals over baseline, during 5 minute treatment with 1.4 mM sodium salicylate (SS) and during the washout period. Inserts A, B, and C show typical spiking pattern observed during 1-s intervals during baseline, SS and washout periods.

Figure 3

Effect of 5 minute treatment with 1.4 mM salicylate (SS) on fusiform cells. (A) Mean spontaneous spike rates (N=6; +/− SE). (B) Mean rate evoked by a +126 pA depolarization current (N=12; +/− SE). The curve shows the average of normalized spike rates across all cells recorded under this condition. * indicates points significantly different from baseline, which is a set of normalized spike rates during the first 4 minutes of each cell.

Figure 4

Effect of 5 minutes of 1.4 mM salicylate (SS) on cartwheel cells. Typical ‘complex spikes’ used to physiologically classify cartwheel cells. (A) Mean spontaneous spike rates (N=7, +/− SE). None of the individual post-treatment points were significantly different from baseline. (B) Mean rate evoked by a +126 pA depolarization current (N=6, +/− SE). None of the individual post-treatment points were significantly different from baseline.

Figure 5

Effect of 3 minutes of 1.4 mM sodium salicylate (SS) on fusiform cells. (A) Mean spontaneous spike rate (N=5; +/− SE); none of the individual points were significantly different from baseline. (B) Mean spike rates evoked by +126 pA depolarization current (N= 8; +/− SE); none of the individual points were significantly different from baseline.

Figure 6

Effect of 5 minutes of 5 mM sodium salicylate (SS) on fusiform cells. (A) Mean spontaneous spike rate (N= 5; +/− SE); none of the individual points were significantly different from baseline. (B) Mean fusiform spike rate evoked by +126 pA depolarization current (N= 10; +/− SE); * indicate points significantly difference from pre-SS baseline.

Figure 7

Effect of 1.4 mM sodium salicylate (SS) on mean (n=8; +/− SE) of the integral of IPSC recorded from fusiform cells; * indicate points significantly difference from pre-SS baseline.