Epilepsy & Behaviour lab
Epilepsy, Stress, Behaviour, Cognition, Schizophrenia, Animal models, Anti-epileptogenic strategies, translational medical research
Group Leader - A/Prof Nigel Jones
To explore relationships between epilepsy and its psychiatric comorbidities, and to develop disease-modifying therapies targeting underlying biological mechanisms. In addition, we aim to understand the cellular and biological basis of cognitive dysfunction in disorders such as schizophrenia.
Our research utilises discovery science approaches to explore animal behaviour in the context of health and disease. The primary goal of the lab is to understand the pathophysiological mechanisms which cause neurological and neuropsychiatric disorders, particularly epilepsy, cognitive disorders and mental health conditions. We employ of a range of advanced behavioural tests of cognition, anxiety, and depression, coupled with in vivo electrophysiology, molecular biology, in vivo imaging, opto/chemogenetic, immunocytochemical and transgenic methods to achieve this goal. We also study the role and influence of neuronal oscillations in cognitive behaviours in physiological circumstances, using sophisticated behavioural tasks and high-end electrophysiological recordings.
Chronic stress is strongly linked to the development of psychiatric disturbances, such as depression and anxiety disorders. Interestingly, these disorders are prevalent in a high proportion of people suffering from epilepsy. Recent literature suggests that environmental exposures such as stress may also contribute to the development of epilepsy. This project aims to investigate this hypothesis and its underlying mechanisms using valid animal models, with a parallel focus on anxiety and depression-like behaviour.
People with epilepsy suffer from seizures - acute episodes of excessive and synchronous brain activity. Stress is the most widely reported precipitant of these seizures in patients. Why does stress seem to trigger seizures in patients? Stress hormones do affect brain function and excitability, and so these appear as likely candidates to mediate this effect of stress. This project will utilise valid animal models of epilepsy to explore how stress triggers seizures. We will study how the epileptic brain responds to stress, which stress hormones are contributors to the effects of stress, and whether blocking stress hormones can reduce the incidence of seizures following stressful episodes. This may lead to new generation of situational anti-seizure medications.
How do brain waves control cognitive processes? Using a combination of in vivo electrophysiology and sophisticated cognitive paradigms of working memory and attention, coupled with genetically modified mice, this project will record brain waves (local field potentials) and single unit activity during cognitive performance to attempt to answer this fundamental question. Several projects are ongoing. These include (1) deep characterisation of neuronal oscillatory patterns occurring during behaviour in different key brain regions; (2) manipulation of brain activity using optogenetic and chemogenetic technologies to infer causal consequences; (3) development of targeted pharmacotherapies to restore aberrant brain wave activity as potential treatment options for disorders with cognitive symptoms.
NMDA receptors are brain ion channels involved in a range of cognitive functions. NMDA receptor antagonists block the opening of these channels, and cause disturbances to a range of cognitive processes, including working memory. In addition, NMDA receptor antagonists distort brain waves, especially high frequency brain waves, and this consequence may be critical to the effects on cognition. This project seeks to understand the mechanisms of how NMDA receptor antagonists create cognitive disturbance, with a focus on neural oscillations. Using a variety of genetically modified mice coupled with high fidelity in vivo electrophysiology and pharmacology, we will study oscillations during cognitive processing in the presence of NMDA receptor antagonists to attempt to identify the cellular mechanisms of action of these drugs.
A recent series of press reports have suggested that sugary drinks may impair cognition in rodents. However, these studies use rudimentary assays for cognition with questionable translational relevance to human populations. This project will use touchscreen-based cognitive assays of working memory and spatial learning, tasks which are analogous to those used in clinical psychology to determine the impact of sugar on these cognitive domains. The cognitive studies will be complemented with in vivo measures of electrophysiology with an aim to investigate a potential mechanism whereby sugar may impact brain function.
Current Competitive Project Funding:
- NHMRC Project grant APP1157353 (2019-2022): NC Jones, A Pitkanen. Antidepressants in Epilepsy
- NHMRC Project grant APP1156733 (2019 – 2021): NC Jones; Functional disconnections in schizophrenia
- NHMRC Project grant APP1105666 (2016 – 2020): A McCluskey, PJ Robinson, NC Jones; A new approach for treating intractable epilepsy
- NIH/NINDS Centre Without Walls NINDS RFA-NS-16-012 (2018-2022): NC Jones (Investigator) The Epilepsy Bioinformative study for antiepileptogenic therapy (EpiBioS4Rx)
- Monash University Establishment grant (2018 – 2022): NC Jones
All recent publications can be seen at Orcid
Selected recent publications
All recent publications can be seen at Orcid
Click on tabs below for a list of publications in each area
- P Thergarajan, JA Hamilton, TJ O’Brien, I Ali, NC Jones. Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity. Epilepsia, v.61(2), 203-215, 2020
- S Carron, G Dezsi, E Ozturk, J Nithianantharajah, NC Jones. Cognitive deficits in a rat model of temporal lobe epilepsy using touchscreen‐based translational tools. Epilepsia, v. 60(8), pp. 1650-1660, 2019
- C Li, J Silva, E Ozturk, G Dezsi, TJ. O’Brien, T Renoir, NC Jones. Chronic fluoxetine treatment accelerates kindling epileptogenesis in mice independently of 5-HT2A receptors, Epilepsia, v59(7), e114-119, 2018.
- S-J Liu, Y Shen, S Shultz, A Nguyen, C Hovens, P Adlard, A Bush, J Chan, P Kwan, T O’Brien, NC Jones. Epileptogenesis is exacerbated by hyperphosphorylation of tau in mice. Epilepsia, v. 58(9), e136-141, 2017
- G Dezsi, E Ozturk, M Salzberg, M Morris, T O'Brien, NC Jones. Environmental enrichment imparts disease-modifying and transgenerational effects on genetically-determined epilepsy and anxiety. Neurobiology of Disease. v.93, p:129-36, 2016.
- S-J Liu, P Zheng, DK Wright, G Dezsi, E Braine, T Nguyen, NM Corcoran, LA Johnston, CM Hovens, JN Mayo, M Hudson, SR Shultz, NC Jones, TJ O’Brien, Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau. Brain v.139, p1919-38, 2016
- MR Hudson, E Sokolenko, TJ O’Brien, NC Jones. NMDA receptors on parvalbumin-positive interneurons and pyramidal neurons both contribute to MK-801 induced gamma oscillatory disturbances: Complex relationships with behaviour. Neurobiology of Disease, v.134, 104625, 2020.
- E Sokolenko, MR Hudson, J Nithianantharajah, NC Jones. The mGluR2/3 agonist LY379268 reverses NMDA receptor antagonist effects on cortical gamma oscillations and phase coherence, but not working memory impairments, in mice. Journal of Psychopharmacology, v.33(12), p1588-1599, 2019.
- M Hudson, G Rind, TJ O’Brien, NC Jones. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine. Translational Psychiatry, v.6, e784. 2016