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Multisensory Integration in the Auditory System

Department                           Department of Neuroscience

Principal investigator          Aaron Wong

E-mail address                      a.wong@erasmusmc.nl

Website                                  https://neuro.nl/research/wong

 

Building a Neuronal Zoo in the Inferior Colliculus

Supervisor: Aaron Wong, a.wong@erasmusmc.nl

Gene expression patterns are important to the function of neurons. The neurons in the important auditory hub inferior colliculus (IC) are highly diverse in connectivity and functions [1], which to-date are poorly characterization molecularly [2], [3]. This project aims to put IC neurons in a unified “zoo” with state-of-the-art single cell and spatial transcriptomics analysis. Our pilot analysis of the recently published dataset [4], [5] revealed spatially variable transcription patterns within the IC, which you will further study and characterize. A natural extension would be to perform histological staining and patch-clamp recordings of sub-populations and relate physiology to their gene expression profiles. This study will lay the foundation for future physiological and molecular studies, and generate hypotheses for further research.

Techniques

  • Analysis of single cell and spatial transcriptomics data
  • Data analysis in python or R
  • Immunohistochemistry and/or in situ hybridization techniques on brain tissue
  • In vivo viral labelling OR patch-clamp electrophysiology in brain slices

Further reading

[1] D. L. Oliver, “Neuronal organization in the inferior colliculus,” in The inferior colliculus, J. A. Winer and C. E. Schreiner, Eds., New York: Springer, 2005, pp. 69–114.

[2] A. C. Drotos and M. T. Roberts, “Identifying neuron types and circuit mechanisms in the auditory midbrain,” Hearing Research, vol. 442, p. 108938, Feb. 2024, doi: 10.1016/j.heares.2023.108938.

[3] M. Liu, Y. Wang, L. Jiang, X. Zhang, C. Wang, and T. Zhang, “Research progress of the inferior Colliculus: From Neuron, neural circuit to auditory disease,” Brain Research, vol. 1828, p. 148775, Apr. 2024, doi: 10.1016/j.brainres.2024.148775.

[4] Z. Yao et al., “A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain,” Nature, vol. 624, no. 7991, pp. 317–332, Dec. 2023, doi: 10.1038/s41586-023-06812-z.

[5] M. Zhang et al., “Molecularly defined and spatially resolved cell atlas of the whole mouse brain,” Nature, vol. 624, no. 7991, Art. no. 7991, Dec. 2023, doi: 10.1038/s41586-023-06808-9.

 

Modelling sound-evoked responses in the auditory midbrain at a neuronal level

Supervisor: Aaron Wong, a.wong@erasmusmc.nl

Sound processing takes place in a series of brain regions, extracting information at increasing levels of abstraction, e.g. from sound frequencies to identity of a speaker. To understand how each brain region achieves this, we often can refer to computational modelling. The inferior colliculus is a sub-cortical auditory region which integrates information from many earlier brainstem nuclei. Our lab has collected a large number of recordings from the inferior colliculus in response to a variety of auditory stimuli [1], [2]. In this project, you will attempt to create computation models to explain these responses, building from basic auditory nerve models e.g., [3] to more complex, circuit-inspired models e.g., [4].

Techniques

  • Programming in Matlab or python
  • Modelling neuronal activity with computational model

Further reading

  1. M. M. van den Berg, A. B. Wong, G. Houtak, R. S. Williamson, and J. G. G. Borst, “Sodium salicylate improves detection of amplitude-modulated sound in mice,” iScience, vol. 27, no. 5, Apr. 2024, doi: 10.1016/j.isci.2024.109691.
  2. M. M. van den Berg, E. Busscher, J. G. G. Borst, and A. B. Wong, “Neuronal responses in mouse inferior colliculus correlate with behavioral detection of amplitude-modulated sound,” Journal of Neurophysiology, vol. 130, no. 3, pp. 524–546, Sep. 2023, doi: 10.1152/jn.00048.2023.
  3. I. C. Bruce, Y. Erfani, and M. S. A. Zilany, “A phenomenological model of the synapse between the inner hair cell and auditory nerve: Implications of limited neurotransmitter release sites,” Hearing Research, vol. 360, pp. 40–54, Mar. 2018, doi: 10.1016/j.heares.2017.12.016.
  4. L. H. Carney and J. M. McDonough, “Nonlinear auditory models yield new insights into representations of vowels,” Atten Percept Psychophys, vol. 81, no. 4, pp. 1034–1046, May 2019, doi: 10.3758/s13414-018-01644-w.

 

Hearing touches and vibrations: somatosensory signal to the auditory midbrain

Supervisors: Aaron Wong & Blom Kraakman, a.wong@erasmusmc.nl & b.kraakman@erasmusmc.nl

Sensory systems allow us to detect the world around us. The inferior colliculus (IC) is a major station of the ascending auditory pathway, but interestingly also receives inputs from somatosensory regions such as the somatosensory cortex, dorsal column nuclei and trigeminal nuclei. However, what information these connections convey and their function remain mysterious. In this project, you will target somatosensory neurons in the IC and characterize their activities in physiological experiments. Further identification can be done using a combination of viral tracers and optogenetics. The identification of somatosensory stimuli that best activate these somatosensory neurons will aid in distinguishing between competing hypotheses (e.g. suppression of self-generated sounds or to aid in orientation to sounds) in the function of this circuit.

Techniques

  • Microsurgery techniques (and viral injections)
  • Multielectrode recording (in combination with optogenetics)
  • Data analysis and programming in Matlab, with utilization of openly available packages (e.g. Kilosort)

Further reading

  1. Lesicko, A.M. et al. (2016) Connectional modularity of top-down and bottom-up multimodal inputs to the lateral cortex of the mouse inferior colliculus. J Neurosci 36, 11037–11050
  2. Lohse, M. et al. (2020) Subcortical Circuits Mediate Communication Between Primary Sensory Cortical Areas. DOI: 10.1101/2020.04.28.064857
  3. Louthan, A. et al. (2020) Multi-sensory (auditory and somatosensory) pre-pulse inhibition in mice. Physiol Behav 222, 112901
  4. Turecek, J. et al. (2022) The encoding of touch by somatotopically aligned dorsal column subdivisions. Nature 612, 310–315
  5. Wu, C. et al. (2015) Listening to another sense: somatosensory integration in the auditory system. Cell Tissue Res 361, 233–250
  6. Gruters, K.G. and Groh, J.M. (2012) Sounds and beyond: multisensory and other non-auditory signals in the inferior colliculus. Front Neural Circuits 6, 96