Dopamine modulates auditory responses in the inferior colliculus in a heterogeneous manner

Abstract

Perception of complex sounds such as speech is affected by a variety of factors, including attention, expectation of reward, physiological state, and/or disorders, yet the mechanisms underlying this modulation are not well understood. Although dopamine is commonly studied for its role in reward-based learning and in disorders, multiple lines of evidence suggest that dopamine is also involved in modulating auditory processing. In this study, we examined the effects of dopamine application on neuronal response properties in the inferior colliculus (IC) of awake mice. Because the IC contains dopamine receptors and nerve terminals immunoreactive for tyrosine hydroxylase, we predicted that dopamine would modulate auditory responses in the IC. We recorded single-unit responses before, during, and after the iontophoretic application of dopamine using piggyback electrodes. We examined the effects of dopamine on firing rate, timing, and probability of bursting. We found that application of dopamine affected neural responses in a heterogeneous manner. In more than 80 % of the neurons, dopamine either increased (32 %) or decreased (50 %) firing rate, and the effects were similar on spontaneous and sound-evoked activity. Dopamine also either increased or decreased first spike latency and jitter in almost half of the neurons. In 3/28 neurons (11 %), dopamine significantly altered the probability of bursting. The heterogeneous effects of dopamine observed in the IC of awake mice were similar to effects observed in other brain areas. Our findings indicate that dopamine differentially modulates neural activity in the IC and thus may play an important role in auditory processing.

FIG. 1

Dopamine has heterogeneous effects on IC neurons. A Example neuron in which dopamine application increased the firing rate. The first three panels are PSTHs of that neuron's responses to 300 presentations of a 100-ms 24-dB sound pressure level (SPL) broadband noise stimulus (horizontal bar) during control, dopamine application, and recovery periods. The fourth panel represents firing rate throughout the recording period. Each point represents the average firing rate to 300 stimulus presentations. The bar labeled DA represents time of dopamine application. B Example neuron that decreased its firing rate during dopamine application. Same conventions as in A except that the stimulus was a 100-ms 65-dB SPL 18-kHz tone (horizontal bar) that was presented 200 times at each time point. C Example neuron that showed no change in its firing rate during dopamine application. Same conventions as in A except that the stimulus was a 100-ms 25-dB SPL 9-kHz tone (horizontal bar) that was presented 120 times. D Normalized change in response rate with dopamine application for the sample of 28 neurons. The mean number of spikes/trial during dopamine application was divided by the mean number of spikes/trial before dopamine. The majority of neurons showed a significant change in firing rate with dopamine application. Open bars represent neurons showing a significant effect of dopamine. Filled bars represent neurons that did not show a significant effect of dopamine. Values less than 1.0 represent decreases in response strength, and values greater than 1.0 represent increases in response strength.

FIG. 2

Dopamine modulates spontaneous activity and sound-evoked firing similarly. A An example neuron that showed increased spontaneous and evoked firing rates with the application of dopamine. Same neuron as in Figure 1A. A1 PSTH showing time points where spontaneous and evoked firing rates were calculated. A2–3 Time courses of spontaneous and evoked firing rate throughout the recording period. Each point represents the average firing rate to 300 stimulus presentations. B An example neuron that showed decreased spontaneous and evoked firing rates with the application of dopamine. Same neuron as in Figure 1B. B1 PSTH showing time points where spontaneous, suppressed, and offset firing rates were calculated. B2–4 Time courses of spontaneous, evoked, and offset firing rates throughout the recording period. Each point represents the average firing rate to 200 stimulus presentations. C Scatter plot of normalized change in spontaneous firing rate versus normalized change in evoked firing rate in response to dopamine shows that dopamine affected spontaneous and evoked firing in the same direction.

FIG. 3

Dopamine affects first spike latency and jitter. A Raster plots of an example neuron showing that dopamine application could increase first spike latency. Stimulus was a 50-dB SPL 23-kHz tone. B Raster plots of an example neuron showing that dopamine application could decrease first spike latency. Stimulus was a 70-dB SPL downward FM sweep with center frequency of 15 kHz and bandwidth of 6 kHz. The bar below the traces indicates acoustic stimulus. Only the first spike is shown for each trial. C Scatter plot illustrating mean first spike latency in the presence of dopamine versus that under control conditions. In some neurons, dopamine increased mean first spike latency (open squares; P < 0.05); in other neurons, dopamine decreased mean latency (open circles; P < 0.05). The remaining neurons showed no significant effect of dopamine on latency (filled circles; P > 0.05). D Scatter plot illustrating the standard deviation of first spike latency (jitter) during dopamine application plotted against the jitter under control conditions. Same symbols as in C. E Scatter plot of the normalized effect of dopamine on jitter plotted against the normalized effect of dopamine on latency. Changes in jitter and latency were highly correlated. F Scatter plot of the normalized effect of dopamine on the mean number of sound-evoked spikes per trial plotted against the normalized effect of dopamine on mean first spike latency. The change in mean evoked firing was inversely correlated with the change in latency.

FIG. 4

Dopamine can modulate burst firing. A Voltage traces from individual trials from an example neuron showing single spikes during control and recovery (dopamine retained) and an increase in burst firing during dopamine application. The horizontal bar indicates time of the 24-dB SPL broadband noise stimulus. B Voltage traces from individual trials from an example neuron showing bursting during control and recovery (dopamine retained) and a decrease in burst firing during dopamine application. The horizontal bar indicates time of the 25-dB SPL 16-kHz (best frequency) tone.