Browsing by Subject "Inferior Colliculi"
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Item Open Access An operant-based detection method for inferring tinnitus in mice.(Journal of neuroscience methods, 2017-11) Zuo, Hongyan; Lei, Debin; Sivaramakrishnan, Shobhana; Howie, Benjamin; Mulvany, Jessica; Bao, JianxinBackground
Subjective tinnitus is a hearing disorder in which a person perceives sound when no external sound is present. It can be acute or chronic. Because our current understanding of its pathology is incomplete, no effective cures have yet been established. Mouse models are useful for studying the pathophysiology of tinnitus as well as for developing therapeutic treatments.New method
We have developed a new method for determining acute and chronic tinnitus in mice, called sound-based avoidance detection (SBAD). The SBAD method utilizes one paradigm to detect tinnitus and another paradigm to monitor possible confounding factors, such as motor impairment, loss of motivation, and deficits in learning and memory.Results
The SBAD method has succeeded in monitoring both acute and chronic tinnitus in mice. Its detection ability is further validated by functional studies demonstrating an abnormal increase in neuronal activity in the inferior colliculus of mice that had previously been identified as having tinnitus by the SBAD method.Comparison with existing methods
The SBAD method provides a new means by which investigators can detect tinnitus in a single mouse accurately and with more control over potential confounding factors than existing methods.Conclusion
This work establishes a new behavioral method for detecting tinnitus in mice. The detection outcome is consistent with functional validation. One key advantage of mouse models is they provide researchers the opportunity to utilize an extensive array of genetic tools. This new method could lead to a deeper understanding of the molecular pathways underlying tinnitus pathology.Item Open Access Detection of single mRNAs in individual cells of the auditory system.(Hearing research, 2018-09) Salehi, Pezhman; Nelson, Charlie N; Chen, Yingying; Lei, Debin; Crish, Samuel D; Nelson, Jovitha; Zuo, Hongyan; Bao, JianxinGene expression analysis is essential for understanding the rich repertoire of cellular functions. With the development of sensitive molecular tools such as single-cell RNA sequencing, extensive gene expression data can be obtained and analyzed from various tissues. Single-molecule fluorescence in situ hybridization (smFISH) has emerged as a powerful complementary tool for single-cell genomics studies because of its ability to map and quantify the spatial distributions of single mRNAs at the subcellular level in their native tissue. Here, we present a detailed method to study the copy numbers and spatial localizations of single mRNAs in the cochlea and inferior colliculus. First, we demonstrate that smFISH can be performed successfully in adult cochlear tissue after decalcification. Second, we show that the smFISH signals can be detected with high specificity. Third, we adapt an automated transcript analysis pipeline to quantify and identify single mRNAs in a cell-specific manner. Lastly, we show that our method can be used to study possible correlations between transcriptional and translational activities of single genes. Thus, we have developed a detailed smFISH protocol that can be used to study the expression of single mRNAs in specific cell types of the peripheral and central auditory systems.Item Open Access Distribution of eye position information in the monkey inferior colliculus.(Journal of neurophysiology, 2012-02) Bulkin, David A; Groh, Jennifer MThe inferior colliculus (IC) is thought to have two main subdivisions, a central region that forms an important stop on the ascending auditory pathway and a surrounding shell region that may play a more modulatory role. In this study, we investigated whether eye position affects activity in both the central and shell regions. Accordingly, we mapped the location of eye position-sensitive neurons in six monkeys making spontaneous eye movements by sampling multiunit activity at regularly spaced intervals throughout the IC. We used a functional map based on auditory response patterns to estimate the anatomical location of recordings, in conjunction with structural MRI and histology. We found eye position-sensitive sites throughout the IC, including at 27% of sites in tonotopically organized recording penetrations (putatively the central nucleus). Recordings from surrounding tissue showed a larger proportion of sites indicating an influence of eye position (33-43%). When present, the magnitude of the change in activity due to eye position was often comparable to that seen for sound frequency. Our results indicate that the primary ascending auditory pathway is influenced by the position of the eyes. Because eye position is essential for visual-auditory integration, our findings suggest that computations underlying visual-auditory integration begin early in the ascending auditory pathway.Item Open Access Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant.(The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016-05) Pages, Daniel S; Ross, Deborah A; Puñal, Vanessa M; Agashe, Shruti; Dweck, Isaac; Mueller, Jerel; Grill, Warren M; Wilson, Blake S; Groh, Jennifer MUnderstanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 μA, 100-300 Hz, n = 172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals' judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site compared with the reference frequency used in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site's response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency-tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts.Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech understanding was limited for the subjects and this limitation is thought to be partly due to challenges in harnessing the sound frequency representation in the IC. Here, we tested the effects of IC stimulation in monkeys trained to report the sound frequencies they heard. Our results indicate that the IC can be used to introduce a range of frequency percepts and suggest that placement of a greater number of electrode contacts may improve the effectiveness of such implants.Item Open Access Single neurons may encode simultaneous stimuli by switching between activity patterns.(Nature communications, 2018-07-13) Caruso, Valeria C; Mohl, Jeff T; Glynn, Christopher; Lee, Jungah; Willett, Shawn M; Zaman, Azeem; Ebihara, Akinori F; Estrada, Rolando; Freiwald, Winrich A; Tokdar, Surya T; Groh, Jennifer MHow the brain preserves information about multiple simultaneous items is poorly understood. We report that single neurons can represent multiple stimuli by interleaving signals across time. We record single units in an auditory region, the inferior colliculus, while monkeys localize 1 or 2 simultaneous sounds. During dual-sound trials, we find that some neurons fluctuate between firing rates observed for each single sound, either on a whole-trial or on a sub-trial timescale. These fluctuations are correlated in pairs of neurons, can be predicted by the state of local field potentials prior to sound onset, and, in one monkey, can predict which sound will be reported first. We find corroborating evidence of fluctuating activity patterns in a separate dataset involving responses of inferotemporal cortex neurons to multiple visual stimuli. Alternation between activity patterns corresponding to each of multiple items may therefore be a general strategy to enhance the brain processing capacity, potentially linking such disparate phenomena as variable neural firing, neural oscillations, and limits in attentional/memory capacity.Item Open Access Systematic mapping of the monkey inferior colliculus reveals enhanced low frequency sound representation.(Journal of neurophysiology, 2011-04) Bulkin, David A; Groh, Jennifer MWe investigated the functional architecture of the inferior colliculus (IC) in rhesus monkeys. We systematically mapped multiunit responses to tonal stimuli and noise in the IC and surrounding tissue of six rhesus macaques, collecting data at evenly placed locations and recording nonresponsive locations to define boundaries. The results show a modest tonotopically organized region (17 of 100 recording penetration locations in 4 of 6 monkeys) surrounded by a large mass of tissue that, although vigorously responsive, showed no clear topographic arrangement (68 of 100 penetration locations). Rather, most cells in these recordings responded best to frequencies at the low end of the macaque auditory range. The remaining 15 (of 100) locations exhibited auditory responses that were not sensitive to sound frequency. Potential anatomical correlates of functionally defined regions and implications for midbrain auditory prosthetic devices are discussed.