Research

Our aim is to understand how information is processed in a multisensory circuit and relate this to the control of behaviour, and perception. We primarily study synaptic transmission, synaptic plasticity and intrinsic excitability in an auditory brainstem nucleus (the dorsal cochlear nucleus) integrating auditory nerve and multisensory inputs (Fig. 1A), using electrophysiological and morphological approaches. We have discovered (Fig. 1B) that:

  • Principal fusiform cell intrinsic excitability is primarily dysregulated after acoustic over-exposure leading to hearing loss, due to the downregulation of Kv3 K+ channels (Fig. 1B1) (Pilati et al., 2009).
  • Auditory nerve dysmyelination is related to hearing deficits (Fig. 1B2)  (Pilati et al., 2012) and (Tagoe et al., 2014).
  • Following acoustic over-exposure, there is an increase in glutamatergic synaptic inputs from the vestibular system (Fig. 1B3) (Barker et al., 2012).
  • Long-term potentiation at multisensory parallel fibres can be impaired (Fig. 1B3), and this is accompanied by a deficit in the detection of gaps in background sound (an experimental model for tinnitus) (Tagoe et al., 2017).

 

Pic_multisensory_circuit

Figure 1A & 1B: AbbreviationsCwC: cartwheel cell, DCN: dorsal cochlear nucleus,DL: deep layer, FL: fusiform layer, GC: granule cell, ML: molecular layer, TvC:  tuberculo-ventral cell, VCN: ventral cochlear nucleus.

Our ongoing work aims at determining how modulation of synaptic transmission relates to action potential firing and temporal encoding (Olsen et al., 2018). We have also shown that synaptic release is strongly modulated by NMDA receptors and Kv3 K+ channels, demonstrating the fine-scale interplay between sub-cellular information and the network connectivity in the brain. We are now dissecting the functional impact of this interplay to better understand how it affects auditory processing and multisensory integration. Our research is integrated within ‘Mechanisms of Animal Behaviour’ Research Strand (MoAB) which provides support for neurobiology and behaviour researchers within the Department of Neuroscience, Psychology and Behaviour.

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Current Lab Member

Pic_Masa_SventMasa Svent is a PhD student funded by Midlands Integrative Biosciences (Doctoral) Training Partnership (MIBTP). Her project involves the presynaptic contribution of NMDA receptor subunits (e.g. NR2A, NR2B, NR2C) to auditory and multisensory synapses in the auditory brainstem dorsal cochlear nucleus. Presynaptic Ca2+ imaging is performed in collaboration with Nick Hartell.

 

Past lab members

Pic_Tim_OlsenTim Olsen is a CASE PhD student funded by MRC and Autifony Therapeutics Ltd. His studies showed the role of Kv3 K+ channels in modulating temporal encoding in the dorsal cochlear nucleus (Olsen et al., 2018). Tim demonstrated that a sparse distribution of Kv3 K+ channels on pre-synaptic boutons is responsible for the increased coherence of fusiform cell spike timing, observed upon Kv3 K+channel positive modulation (study in collaboration with Nick Hartell). Tim is currently working as a postdoctoral researcher at the University of California, San Francisco, studying the function of cortical interneurons in the processing of sound embedded in background noise.

 

Pic_Alberto_CappuroAlberto Cappuro is a post-doctoral research associate who was involved in setting up and programming the gap-induced prepulse inhibition of the acoustic startle reflex in Human (studies in collaboration with Doug Barrett). Alberto is a contributing author to Olsen et al., 2018. and a honorary research fellow. He is currently a post-doctoral research associate at University of Newcastle, studying cellular excitability dysregulated in pain.


Pic_Jennifer_SchofieldJennifer Schofield is a senior research technician who performed behavioural prepulse inhibition tests. Studies were funded by a project grant funded by Action on Hearing Loss TRIH to University of Newcastle (M. Cunningham, A. Reiss), Autifony Therapeutics Ltd (C. Large) and University of Leicester (M. Hamann). Studies aimed at common mechanisms in tinnitus and epilepsy. Jenny is currently working with Leicester Drug Discovery and Diagnostics (LD3).

 

Pic_EMPTYAnthony Oakden is a research technician who performed behavioural prepulse inhibition tests on a project grant funded by British Tinnitus Association to M. Hamann and N. Sylvius (University of Leicester). Studies aimed at investigating the presence of microRNAs specific to tinnitus.

 

 

Pic_Thomas_TagoeThomas Tagoe undertook a PhD funded by Action on Hearing Loss characterising dysmyelination in noise-induced hearing loss (Tagoe et al., 2014) and identifying plasticity deficits in an experimental model of tinnitus (Tagoe et al., 2017). Thomas is currently a lecturer at the University of Ghana and co-founder of GhScientific, a science based NGO focused on promoting STEM based content within Ghana through public engagement and outreach activities. His work at University of Ghana has won support from the Wellcome Trust, the International Society of Neurochemistry and the International League Against Epilepsy.

 

Pic_EMPTYJulie-Myrtille Bourgognon is a post-doctoral research associate funded by Nottingham-Leicester Hearing Loss and Tinnitus Neuroscience Consortium and University of Leicester. Her studies involved comparing the properties of the gap-induced prepulse inhibition of the acoustic startle reflex as an experimental model of tinnitus, in different rat strains. Julie-Myrtille is currently working as a post-doctoral research associate at University of Glasgow.


Pic_Matt_BarkerMatt Barker is a departmental technician when he did an MSc, setting up a method for delivering macromolecules focally (Barker et al., 2009), and using this method, identifying synaptic projections from the vestibular system to the dorsal cochlear nucleus, modulated after exposure to loud sound (Barker et al., 2012). Matt is currently technical service manager at University of Leicester.

 

Pic_Nadia_PilatiNadia Pilati is a PhD student funded by GlaxoSmithkline UK. Nadia developed a method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture (Pilati et al., 2008). Her studies demonstrated that exposure to loud sound triggers bursts in dorsal cochlear nucleus fusiform cells due to a downregulation of Kv3 K+ currents (Pilati et al., 2012A) and affects differentially synaptic transmission originating from the auditory nerve or multisensory inputs  (Pilati et al., 2012B). Nadia is currently a senior scientist and head of lab at Autifony Therapeutics Ltd.

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Department of Neuroscience, Psychology and Behaviour
University of Leicester
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T: +44 (0)116 252 2922
E: npbenquiries@le.ac.uk

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