Neurobiology

The Eyles laboratory focuses on how early epidemiologically-validated risk factors for schizophrenia and autism, change the way the brain develops and functions with a particular focus on dopamine systems. We also want to understand how the adolescent brain progresses towards a hyperdopaminergic state.

Lab History

  • In 2010 we established that low maternal levels of vitamin D was a risk factor for schizophrenia and autism in newborn dried blood spots using an assay developed by the group. This has initiated 15 international collaborations funded by 2 NIH grants and 3 NHMRC grants.
  • Via our collaboration in Zurich we have now shown vitamin D is capable of blocking all symptom phenotypes in a maternal immune activation model of schizophrenia. (funded by 2 NHMRC grants).
  • Our latest studies show that maternal vitamin D deficiency, maternal immune activation and prenatal hypoxia (well validated risk factors for schizophrenia) all affect the early differentiation, positioning and connectivity of dopamine neurons. This exciting discovery may mean that the cause of schizophrenia (where there is abnormal dopamine signalling) may be due to very early alterations in the ontogeny of these neurons. We are now focused on the exact convergent mechanisms. (funded by multiple NHMRC grants).
  • We have recently shown the molecular processes behind how maternal vitamin D deficiency increases testosterone in developing brains. This work may have broader implications for why autism is more common in boys. (funded by 1 NHMRC grant)
  • Sub-cortical dopamine systems are pre-symptomatically hyperactive in schizophrenia selectively in a circuit known as the dorsal striatum. Using a novel genetic construct used to treat Parkinson’s disease (Lund University) we have now developed a model of this important aspect of the schizophrenia prodrome.  In collaboration with the clinical group who first showed that dopamine abnormalities were presymptomatic in patients at King’s College London we have now been able to completely replicate this circuit abnormality progressively across late adolescence in an animal model. We are now using this model to understand:
    • how interconnected circuits become dysfunctional in schizophrenia,
    • how this may produce hyperinflammatory conditions in the midbrain
    • how such circuits interact with stress and psychoactive compounds
    • To trial potential prophylactic agents to block/retard the onset of schizophrenia. (funded by 1 NHMRC grant)

Group leader

Professor Darryl Eyles

Professor Darryl Eyles

Conjoint Professor, Queensland Brain Institute

  +61 7 334 66370
  d.eyles@uq.edu.au
  UQ Researcher Profile

 

The University of Queensland

  • Professor John McGrath, QBI
  • Associate Professor Tom Burne, QBI
  • Associate Professor Bruno Van Swinderen, QBI
  • Dr Ethan Scott

National

  • Prof Andrew Whitehouse Telethon Kids Institute Perth, WA
  • Dr. Jake Gratten TRI, Brisbane

International

  • E Fernell Karolinska, Sweden
  • B. Lee Drexel University, USA
  • U. Meyer, ETH Zurich, Switzerland
  • O. Howes Kings college London
  • R. Schmidt, University of California Davis, USA
  • G Windham, Division of Environmental and Occupational Disease Control, USA
  • P Hurst Massey University Auckland NZ.
  • D Kirik Lund University Sweden

We have developed a new animal model of schizophrenia. We elevate dopamine selectively in the dorsal striatum by stereotaxically delivering genetic constructs to the substantia. We call this model Elevated Dopamine in Prodromal Schizophrenia (EDiPs). Our aim is to follow the course and examine the alterations in brain connectivity induced by EDiPS. Our ultimate aim is to intervene to block the disease process.

 

Project 1:  How does EDiPS affect cortical and subcortical connectivity and can we intervene to block EDiPS induced abnormalities in connectivity and behavioural phenotypes?

Project 2:  This project will firstly establish a new and more dopaminergically-selective EDiPS model using a TH-Cre rat and DREADD technology. Secondly, the student will establish whether early post-natal or late (Puberty) stages of brain development represent the critical window for EDiPS-induced phenotypes.

In a second series of studies we have selectively blocked both early features of autism and late characteristic behaviours associated with schizophrenia in the well-described Maternal Immune Activation animal model using the hormonal form of vitamin D.

Project 3:  We now want to understand what neuroprotective mechanisms we have triggered in this model and if we could also replicate these findings using the dietary form of vitamin D.

How to apply

Research Areas

  • Dopamine
  • Schizophrenia Prodrome
  • Autism
  • Brain Development
  • Vitamin D 

Our team

Group Leader


Research Members


Students


Support Staff

  • Ms Pauline Ko

    Principal ResearchFellow (Conjoint)
    Queensland Brain Institute