Institute of Neuroscience

Staff Profile

Dr Bas Olthof

Research Associate

Research

My research is aimed at understanding the neurobiology underlying auditory processing. My PhD thesis focused on the role of nitric oxide signalling in auditory processing in the inferior colliculus, the principal midbrain nucleus of the auditory pathway.

Nitric oxide is catalysed by neuronal nitric oxide synthase (nNOS) a protein that catalyses the conversion of L-Arginine to L-Citrulline and nitric oxide. nNOS is abundant throughout the brain, but expression is especially pronounced in the brainstem nuclei and cerebellum. Of all brainstem nuclei the inferior colliculus expresses the most nNOS, in fact, it expresses more nNOS than all other nuclei combined. Although nNOS has been identified in the IC, the functional properties of nitric oxide signalling in the IC are unknown. nNOS activity has been shown to be upregulated in animal models of tinnitus – the perception of phantom sounds.

Tinnitus is a common, chronic and often disabling condition affecting up to 15% of the adult population. Whilst tinnitus is frequently associated with hearing loss and is more common in the elderly, it can also occur in the absence of hearing loss and can be experienced by younger individuals.  We know that acoustic trauma (loud sounds) and some drugs can induce tinnitus however, our understanding of its neurobiological underpinnings is incomplete. There are currently no effective treatments for tinnitus.  Gaining an understanding of the mechanisms which underlie tinnitus will undoubtedly suggest therapeutic targets and may lead to the development of effective treatments

In my thesis I showed an intriguing reciprocal connection between nNOS and the glutamatergic NMDA receptor. My current research focusses on the descending connections of the auditory cortex to the inferior colliculus. This pathway is proposed to mediate modulatory feedback and plasticity that may underlie predictive coding and auditory attention. Indirect evidence suggests that visual and somatosensory cortices may also project to the inferior colliculus and influence its activity. Although there is strong evidence for cortico-collicular connections, we know little about their organisation: their fields/laminae of origin, the subdivisions of the inferior colliculus they terminate in, and the phenotypes of the cells they target. Moreover, while there is functional evidence that cortical inputs modulate activity in the inferior colliculus, we know almost nothing about the underlying mechanisms. Cortical output neurones are glutamatergic and likely act through AMPA and NMDA receptor subtypes. Both subtypes are present in the inferior colliculus and we have seen that their selective activation influences the activity of inferior colliculus neurons. The inferior colliculus has high levels of nitric oxide synthase and we have shown that NMDA interacts with nitric oxide to modify neuronal activity in this nucleus. In other brain regions NMDA receptor/nitric oxide interactions are key mediators of plasticity.

I use a wide range of techniques to examine the anatomy, biochemistry and function of auditory pathways in rodents. I use in vivo electrophysiology, in vivo microdialysis, optogenetics, in vitro extracellular electrophysiology, behavioural analysis, immunocytochemistry, in situ hybridization, immunohistochemistry, Western blotting and both retrograde and anterograde tract tracing techniques.

Qualifications

Ph.D., Auditory Neuroscience, Newcastle University, United Kingdom

M.Sc., Cognitive Neuroscience, Donders Institute, Radboud University Nijmegen, The Netherlands.

B.Sc., Psychology, Universiteit Twente, Enschede, The Netherlands

Teaching

2017 (Newcastle University)

Undergraduate biomedical science projects 

PSY2009 Methods in Psychology 2A

PSY1011 Research Methods and skills


2016 (Newcastle University)

PSY2009 Methods in Psychology 2A

PSY8061 Advanced research methods for applied psychology

PSY1011 Research Methods and skills

Undergraduate biomedical science projects


2015 (Newcastle University)

PSY2009 Methods in Psychology 2A

CMB1006 Practical skills in biomedical and biomolecular Sciences


2014 (Newcastle University)

PSY2009 Methods in Psychology 2A

2010

Developmental psychology (Universiteit Twente, The Netherlands)


Publications