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Jonathan Witton

Lecturer in Neuroscience

10392 72 7583

Hatherly D.2

Hatherly Building, University of Exeter, Prince of Wales Road, Exeter, EX4 4PS, UK

Overview

Dr Jon Witton is a neurophysiologist interested in how brain circuits support adaptive cognitive behaviours and how this is disrupted by neurodegenerative disease.

Jon graduated from the University of Manchester with a BSc (1st class) in Neuroscience. As part of his degree he spent a year working at the pharmaceutical company Boehringer Ingelheim in Germany. He then moved to the University of Bristol as a PhD student in the groups of Profs Andy Randall and Matt Jones, where he studied mechanisms of neuronal circuit dysfunction in Down syndrome and dementia. After completing his PhD, Jon remained in Bristol as an Alzheimer’s Research UK Fellow with Dr Mike Ashby, studying how functional and structural changes develop in brain circuits during tauopathy-associated dementia.

In 2019 Jon was appointed Lecturer at the University of Exeter

Qualifications

2009, BSc (hons), University of Manchester
204, PhD, Univesrity of Bristol

Grants/Funding:

Alzheimer’s Research UK Fellowship (PI, £196k, 2016-2019)
MRC PhD studentship (Co-I, 90k, 2016-2020)
MRC PhD studentship (Co-I, 90k, 2019-2023)
BBSRC 18ALERT (Co-I; £223k; 2019-2022)

Research

Research interests

Our ability to learn and remember shapes our behaviour, enabling us to adapt to new environments and optimise our performance in situations that we have already experienced. Jon’s research focusses on understanding how neuronal networks enable this cognitive adaptation, and how this ability becomes disrupted in neurodegenerative diseases such as Alzheimer’s disease.

To do this, Jon and his colleagues employ a multilevel systems neuroscience approach, combining in vivo two-photon and micro-endoscopic brain imaging, in vivo extracellular and patch clamp electrophysiology and behavioural analysis to understand how cognitive information is processed in brain circuits across different spatial and temporal scales.

Research projects

Current Projects:

Dysfunctional synaptic and neuronal network encoding in tauopathy-associated dementia.
Relationship between synaptic dysfunction and degeneration in dementia.
Neuron-microglia interactions during neuronal network oscillations.

Publications

Key publications | Publications by category | Publications by year

Publications by category

Journal articles

Randall A, Jackson J, Witton J, Johnson J, Ahmed Z, Ward M, Hutton ML, Isaac JT, O'Neill MJ, Ashby MC, et al (In Press). Altered synapse stability in the early stages of tauopathy. Cell Reports-D-16-02088R2

Walsh C, Ridler T, Garrido MG, Witton J, Randall AD, Brown JT (In Press). Beta bursting in the retrosplenial cortex is a neurophysiological correlate of environmental novelty which is disrupted in a mouse model of Alzheimer’s disease. Abstract.

Ridler T, Witton J, Phillips KG, Randall AD, Brown JT (In Press). Impaired speed encoding is associated with reduced grid cell periodicity in a mouse model of tauopathy. Abstract.

Craig MT, Witton J (2022). A cellular switchboard in memory circuits. Science, 377(6603), 262-263. Abstract. Author URL.

Walsh C, Ridler T, Margetts-Smith G, Garcia Garrido M, Witton J, Randall AD, Brown JT (2022). β Bursting in the Retrosplenial Cortex is a Neurophysiological Correlate of Environmental Novelty Which is Disrupted in a Mouse Model of Alzheimer's Disease. The Journal of Neuroscience, 42(37), 7094-7109.

Meftah S, Witton J, Cavallini A, Murray TK, Jankowski L, Bose S, Ashby M, Brown JT (2020). Identifying early markers of synaptic dysfunction in a mouse model of tauopathy. Alzheimer's & Dementia, 16(S3).

Ridler T, Witton J, Phillips KG, Randall AD, Brown JT (2020). Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy. eLife, 9 Abstract.

Booth CA, Witton J, Nowacki J, Tsaneva-Atanasova K, Jones MW, Randall AD, Brown JT (2016). Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy. J Neurosci, 36(2), 350-363. Abstract. Author URL.

Witton J, Staniaszek L, Bartsch U, Randall AD, Jones MW, Brown JT (2015). Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia. Journal of Physiology, In press Abstract.

Witton J, Padmashri R, Zinyuk LE, Popov VI, Kraev I, Line SJ, Jensen TP, Tedoldi A, Cummings DM, Tybulewicz VLJ, et al (2015). Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome. Nat Neurosci, 18(9), 1291-1298. Abstract. Author URL.

Rodríguez JJ, Noristani HN, Hilditch T, Olabarria M, Yeh CY, Witton J, Verkhratsky A (2013). Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer's disease. Neurosci Lett, 552, 129-134. Abstract. Author URL.

Forsyth LH, Witton J, Brown JT, Randall AD, Jones MW (2012). In Vitro and in Vivo Recording of Local Field Potential Oscillations in Mouse Hippocampus. Curr Protoc Mouse Biol, 2(3), 273-294. Abstract. Author URL.

Witton J, Brown JT, Jones MW, Randall AD (2010). Altered synaptic plasticity in the mossy fibre pathway of transgenic mice expressing mutant amyloid precursor protein. Mol Brain, 3 Abstract. Author URL.

Rodríguez JJ, Witton J, Olabarria M, Noristani HN, Verkhratsky A (2010). Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease. Cell Death Dis, 1(1). Abstract. Author URL.

Randall AD, Witton J, Booth C, Hynes-Allen A, Brown JT (2010). The functional neurophysiology of the amyloid precursor protein (APP) processing pathway. Neuropharmacology, 59(4-5), 243-267. Abstract. Author URL.

Publications by year

In Press

Brady ES, Griffiths J, Andrianova L, Saito T, Saido TC, Randall AD, Tamagnini F, Witton J, Craig MT (In Press). Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal – medial prefrontal cortex circuit during natural sleep in App<sup>NL-G-F</sup>mice.

AbstractIn the early stages of Alzheimer’s disease (AD), the accumulation of the peptide amyloid-β (Aβ) damages synapses and disrupts neuronal activity and leads to disruption of neuronal oscillations associated with cognition. This is thought to be largely due to impairments in CNS synaptic inhibition, particularly via parvalbumin (PV)-expressing interneurons that essential for generating several key oscillations. Research in this field has largely been conducted in mouse models that over-express humanised, mutated forms of AD-associated genes that produce exaggerated pathology. This has prompted the development and use of knock-in mouse lines that express these genes at an endogenous level, such as the AppNL-G-F/NL-G-Fmouse model used in the present study. These mice appear to model the early stages of Aβ-induced network impairments, yet an in-depth characterisation of these impairments in currently lacking. Therefore, using 16 month-old AppNL-G-F/NL-G-Fmice, we analysed neuronal oscillations found in the hippocampal – medial prefrontal cortex (mPFC) during awake behaviour, rapid eye movement (REM) and non-REM (NREM) sleep to assess the extent of network dysfunction. No alterations to gamma oscillations were found to occur in the hippocampus or mPFC during either awake behaviour, REM or NREM sleep. However, during NREM sleep an increase in the amplitude of mPFC spindles and decrease in the power of hippocampal SWRs was identified. The former was associated with a decrease in the density of mPFC PV-expressing interneurons and the latter was accompanied by an increase in the synchronisation of PV-expressing interneuron activity, as measured using two-photon Ca2+imaging. Furthermore, although changes were detected in local network function of mPFC and hippocampus, long-range communication between these regions appeared intact. Altogether, our results suggest that these NREM sleep-specific impairments represent the early stages of circuit breakdown in response to amyloidopathy.

Abstract.

Ridler T, Witton J, Phillips KG, Randall AD, Brown JT (In Press). Impaired speed encoding is associated with reduced grid cell periodicity in a mouse model of tauopathy. Abstract.

2022

Craig MT, Witton J (2022). A cellular switchboard in memory circuits. Science, 377(6603), 262-263. Abstract. Author URL.

2020

Ridler T, Witton J, Phillips KG, Randall AD, Brown JT (2020). Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy. eLife, 9 Abstract.

2016

2015

2013

2012

2010

Jonathan_Witton Details from cache as at 2023-03-21 09:25:29

Refresh publications

External Engagement and Impact

Awards

Elizabeth Blackwell Institute Bridging Fellowship (2019)
Alzheimer’s Research UK Fellowship (2016-2019)
UoB-MRC Centenary Fellowship (2013-2014)

Invited lectures

Alzheimer’s Research UK
University College Cork
University of Edinburgh
University of Bristol

Media Coverage

The Scotsman 04/08/15 Down’s link to part of the brain that affects learning. https://www.scotsman.com/news-2-15012/down-s-link-to-part-of-brain-that-affects-learning-1-3848641
Health Canal 04/08/15 Scientists identify trouble spot in brain linked to learning difficulties in Down syndrome. https://www.healthcanal.com/brain-nerves/brain-diseases/65832-scientists-identify-trouble-spot-in-brain-linked-to-learning-difficulties-in-down-syndrome.html
Daily Express 28/03/17 DEMENTIA BREAKTHROUGH: Earliest stages REVEALED by researchers for first time. https://www.express.co.uk/life-style/health/784851/Dementia-Alzheimers-research-medical-intervention-health
Science Daily 28/03/17 Therapies that target dementia in early stages critical to success. https://www.sciencedaily.com/releases/2017/03/170328145236.htm

Teaching

Teaching responsibilities: (Undergraduate, Postgraduate)

Coding for Medical Scientists (CSC2020): Lecturer
Neural Circuits (CSC2018): Lecturer
Foundations in Neuroscience (CSC2006): Facilitator
Principles in Medical Research (CSC2014): Small group facilitator
Academic Tutor: Year 1 BSc Neuroscience

Modules

2022/23

Supervision / Group

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Profile

Jonathan Witton

Lecturer in Neuroscience

Overview

Qualifications

Research

Research interests

Research projects

Publications

Publications by category

Journal articles

Abstract:Beta bursting in the retrosplenial cortex is a neurophysiological correlate of environmental novelty which is disrupted in a mouse model of Alzheimer’s disease

Abstract:Impaired speed encoding is associated with reduced grid cell periodicity in a mouse model of tauopathy

Abstract:A cellular switchboard in memory circuits.

Abstract:Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy

Abstract:Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

Abstract:Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia

Abstract:Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome.

Abstract:Increased densities of resting and activated microglia in the dentate gyrus follow senile plaque formation in the CA1 subfield of the hippocampus in the triple transgenic model of Alzheimer's disease.

Abstract:In Vitro and in Vivo Recording of Local Field Potential Oscillations in Mouse Hippocampus.

Abstract:Altered synaptic plasticity in the mossy fibre pathway of transgenic mice expressing mutant amyloid precursor protein.

Abstract:Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease.

Abstract:The functional neurophysiology of the amyloid precursor protein (APP) processing pathway.