Serotonergic Modulation of Sensory and Multisensory Processing in Superior Colliculus

in Multisensory Research
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The ability to integrate information across the senses is vital for coherent perception of and interaction with the world. While much is known regarding the organization and function of multisensory neurons within the mammalian superior colliculus (SC), very little is understood at a mechanistic level. One open question in this regard is the role of neuromodulatory networks in shaping multisensory responses. While the SC receives substantial serotonergic projections from the raphe nuclei, and serotonergic receptors are distributed throughout the SC, the potential role of serotonin (5-HT) signaling in multisensory function is poorly understood. To begin to fill this knowledge void, the current study provides physiological evidence for the influences of 5-HT signaling on auditory, visual and audiovisual responses of individual neurons in the intermediate and deep layers of the SC, with a focus on the 5HT2a receptor. Using single-unit extracellular recordings in combination with pharmacological methods, we demonstrate that alterations in 5HT2a receptor signaling change receptive field (RF) architecture as well as responsivity and integrative abilities of SC neurons when assessed at the level of the single neuron. In contrast, little changes were seen in the local field potential (LFP). These results are the first to implicate the serotonergic system in multisensory processing, and are an important step to understanding how modulatory networks mediate multisensory integration in the SC.

Multisensory Research

A Journal of Scientific Research on All Aspects of Multisensory Processing

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Figures

  • Example responses of visual, auditory and audiovisual SC multisensory neurons. Peristimulus-time histograms (PSTHs) from an example visual (A), auditory (B) and audiovisual (C) multisensory neuron showing responsiveness to sensory stimulus presentations before (pre), 10 min following (peri) and 3.5 h following (post) DOI injection. Bar graphs to the right are plotting response per trial (resp/trial) and integrative index (ii) quantifications of the example PTSH shown to the left. The administration of DOI induces an increase in both resp/trial and ii in all three neuronal types. FF: fano factor.

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  • DOI affects unisensory and multisensory responsiveness in deep SC neurons. Average relative responses (A) and fano factor (B) of auditory (left), visual (right), and audiovisual (center) SC neurons to unisensory and multisensory stimulus presentations before (pre) and 10 min following (peri) DOI injection. Responses after administration of DOI (peri) were normalized to unisensory pre-DOI responses to compare populations of neurons. Significance was determined by comparing conditions following DOI addition to the ‘pre’ condition. Asterisks display comparisons of significance, p<0.05, ∗∗p<0.01, ∗∗∗p<0.001. (A) Addition of DOI significantly increased neuronal responses to unisensory and multisensory stimulus presentations. Addition of DOI increased visual neurons’ responses to multisensory stimuli as well as audiovisual neurons’ responses to visual stimulus presentations. (B) Addition of DOI increased fano factor (FF) of visual neurons’ visual and audiovisual responses as well as audiovisual neurons’ auditory responses, while decreasing FF of audiovisual neurons’ multisensory responses.

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  • DOI affects interactive index of multisensory deep SC neurons. (A) Interactive index (ii) of auditory, visual and audiovisual neurons with DOI administration. Interactive index of auditory and visual neurons increased with the addition of DOI. Inset: change in ii (Δii) between pre- and peri-DOI recordings. The greatest change in ii with DOI addition was observed in visual neurons. (B) Interactive index divided between neuronal types as well as RF location. At central RF locations (left), auditory neuron ii was significantly increased with the addition of DOI, whereas at peripheral locations both auditory and visual neuron ii increased with DOI addition. Insets show Δii between pre- and peri-DOI recordings; the greatest change in ii was observed in visual neurons at peripheral RF locations.

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  • DOI effects are more dramatic at peripheral receptive field locations. (A) (top) Relative responses of auditory (left), visual (right), and audiovisual (center) SC neurons from central RF locations. Relative responses of visual neurons to unisensory stimuli increased with DOI addition. (bottom) Fano factor (FF) of auditory (left), visual (right), and audiovisual (center) neurons at central RF locations. FF increased at central locations with DOI addition for visual neurons, whereas FF of audiovisual neurons decreased with the addition of DOI. (B) (top) Relative responses to visual stimuli increased with addition of DOI for both visual and audiovisual neurons at peripheral locations. Audiovisual neurons also exhibited an increase in response to audiovisual stimuli, and a decrease in response to auditory stimuli with addition of DOI at peripheral locations. (bottom) Relative FF at peripheral locations increased for visual neurons with DOI addition while decreasing for audiovisual neurons (right). Significance was determined by comparing conditions following DOI addition to the ‘pre’ condition. Responses after administration of DOI (peri) were normalized to pre-DOI responses to compare populations of neurons. Asterisks display comparisons of significance, p<0.05, ∗∗p<0.01, ∗∗∗p<0.001.

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  • DOI changes SRF of two deep SC multisensory neurons. (A) Pseudo color spatial receptive field (SRF) plots for a visual neuron representing the unisensory (visual, left) and multisensory (right) evoked responses normalized across all locations and all conditions to produce a range from 0 to 1, where 0 represents no response and 1 represents maximum response. Greater responses are depicted as warmer colors and smaller responses are depicted as cooler colors. Dotted outlines on each plot indicate the RF shape pre-DOI (top). (middle) Addition of DOI (peri) increases both overall SRF size and relative magnitude of response in both the visual (left) and audiovisual (right) stimulus conditions. (bottom) The SRF trends back to baseline once DOI action has ceased (post). (B) Contrast plots showing the difference between peri- and pre-DOI application (top) and post- and pre-DOI application (bottom) for both stimulus conditions (visual only, audiovisual). Warmer colors represent more response in the peri- or post-DOI condition compared to the baseline condition. From the plots, there was more and wider responsivity in the peri-DOI condition, which trended to return back to baseline in the post-DOI condition. (C) SRF plots for an auditory neuron. Color representations and scales are the same as in (A). (middle) Addition of DOI (peri) decreases both overall SRF size and relative magnitude of response in both the auditory (left) and audiovisual (right) stimulus conditions. (bottom) The SRF trends to return back to baseline once DOI action has ceased (post). (D) Contrast plots showing the difference between peri- and pre-DOI application (top) and post- and pre-DOI application (bottom) for both stimulus conditions (auditory only, audiovisual). Color representations and scales are the same as in (B).

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  • DOI changes SRFs of a deep SC audiovisual multisensory neuron. (A) Pseudo color spatial receptive field (SRF) plots representing the unisensory (visual, left; auditory, middle) and multisensory (right) evoked responses of an audiovisual neuron pre-DOI application (top) normalized across all locations and all conditions to produce a range from 0 to 1, where 0 represents no response and 1 represents maximum response. This audiovisual neuron showed greater responses to visual as opposed to auditory unisensory stimulus presentations, hence the cooler colors in the auditory SRF plots. Greater responses are depicted as warmer colors and lesser responses are depicted as cooler colors. Dotted outlines on each plot indicate the RF shape pre-DOI. (middle) Addition of DOI (peri) increases both overall SRF size and relative magnitude of response in the unisensory stimulus conditions, but a decrease in overall SRF size and response magnitude in the audiovisual (right) stimulus condition. (bottom) The SRF trends back to baseline once DOI action has ceased (post). (B) Contrast plots showing the difference between peri- and pre-DOI application (top) and post- and pre-DOI application (bottom) for both stimulus conditions (visual only, audiovisual). Warmer colors represent more response in the peri- or post-DOI condition compared to baseline pre conditions. These contrasts indicate less responsivity in the peri-DOI condition, which did not quite trend to return back to baseline in the post-DOI condition.

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  • DOI application evokes minimal changes on local field potential signals. (A) LFP traces from example visual, audiovisual and auditory neurons showing signal responses to auditory (red), visual (blue) and audiovisual (green) stimulus presentations. (B) Relative LFP peak responses of auditory (left), audiovisual (middle), and visual (right) SC neurons to unisensory and multisensory stimulus presentations before (pre) and 10 min following (peri) DOI administration. White bars indicate the predicted peak LFP as determined by the sum of the unisensory peaks (pred peak). Relative local field potential (LFP) peak for auditory (left), audiovisual (middle) and visual (right) neuronal types at central RF locations. Addition of DOI increased visual peaks in visual neurons. (C) At peripheral RF locations, visual peaks were increased in visual neurons.

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  • Depths of single unit recordings of SC multisensory neurons relative to the top of the SC. Auditory (left), visual (middle) and audiovisual (right) multisensory SC neurons were recorded throughout the intermediate and deep SC layers. (A) Auditory (red) and visual (blue) unisensory responses of each neuron. Filled circles indicate an increase in unisensory responsivity with the addition of DOI, and open circles indicate a decrease of unisensory responsivity. In the case of some audiovisual neurons, responsivity to one modality increased with DOI while the other did not. This is shown with a half-filled circle, the color of which corresponds to the modality increased by DOI addition. Neurons located more superficially (i.e., likely in the intermediate SC layers) were more likely to show increases in unisensory responsivity with DOI administration. (B) Multisensory responsivity of the neurons in relation to depth of recording. Filled (green) circles indicate an increase in audiovisual responses with DOI addition while open circles indicate a decrease or no change in responses. Neurons located within more intermediate, as opposed to deep, SC layers more often showed increases in audiovisual response with DOI addition. (C) Multisensory gain of response (interactive index, ii) for each neuron recorded. Grey circles indicate the locations of neurons which did not exhibit a change in ii with the addition of DOI. Filled circles indicate neurons which exhibited a response enhancement and open circles a response depression with DOI injection. Neurons located more superficially more often showed an increase in ii as compared to neurons located in more deep SC layers.

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  • Injection of aCSF does not alter responses of multisensory SC neurons. Relative responses (A), fano factor (B) and interactive index (C) of auditory, visual and audiovisual SC neurons before (pre), 10 min following (peri) and 3.5 h following (post) aCSF injection. Neuronal subtypes are collapsed as there was no effect of neuron type on responses to aCSF injection. Responses were normalized to pre-aCSF responses to compare populations of neurons. (A) Addition of aCSF did not significantly change responses to unisensory (gray) or multisensory (black) stimulus presentations. (B) Addition of aCSF did not alter fano factor (FF) of neuronal responses or (C) interactive index.

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