Allen laboratory: Central cardiovascular regulation

Research Overview

View Professor Allen's latest PubMed publications listing here

Our research group has an overarching interest in how individual neuronal groups in the central nervous system interact to produce behaviours. As model systems, we examine neurons regulating breathing, blood pressure and the heart. This encompasses an interest in neuroscience, particularly how neural groups interact in vivo to generate specific motor patterns, as well as the cardio-respiratory system.

The following sections describe a few of our main areas of current interest.

Which neural pathways are involved in generating cardiovascular diseases?

Neural regulation of sympathetic and parasympathetic activity is clearly altered in cardiovascular diseases such as heart failure. In fact, alteration of this nervous activity is proposed to cause the hypertension that is a major risk factor for the development of these diseases. Yet, the neural circuits that regulate sympathetic and parasympathetic activity are incompletely understood.

Through our research, we are attempting to understand more about this circuitry in order to test fundamental questions such as:

  • Can a centrally-generated increase in sympathetic activity lead to sustained hypertension?
  • Can we modify the progression of cardiovascular diseases by altering neural function?

To answer these questions we are performing:

  • viral transduction studies to alter gene expression in specific groups of neurons
  • specific drug administration to alter activity of certain neuron groups
  • opto- and chemo-genetic approaches to modulate the activity of neurons in vivo

How do neurons interact?

With an estimated one billion neurons in the brain and each neuron potentially receiving information from hundreds of other neurons the potential interactions are mind-boggling. Reduced preparations are commonly used to try and bring the scale of these interactions to understandable proportions.

We are seeking to understand the mechanisms by which one of the simpler mammalian neural circuits works to generate activity. This is the circuitry responsible for the generation of sympathetic activity to blood vessels. We now know the constituent members of the circuit and their function on a broad level. This then brings us to an exciting point where we can look at:

  • how individual neurons generate tonic activity
  • how local synaptic interactions modify function
  • how peptide neurotransmitters/neuromodulators change gain and might affect function in disease.

Understanding the brain renin-angiotensin system

Whilst its existence was suggested over 30 years ago, the brain renin-angiotensin system remains incompletely understood.

  • Is angiotensin generated within the brain? If so, how does this happen when the constituents are present in different cell types (angiotensinogen in astrocytes; renin in very low concentration in some neurons)?
  • Is angiotensin released from presynaptic terminals in response to depolarization- i.e. is it a neurotransmitter?

These fundamental questions remain unanswered despite the fact that angiotensin is known to exert powerful actions in the brain on fluid and electrolyte homeostasis, autonomic activity, neuroendocrine function and neurodegenerative diseases.

Staff

Mariana Melo, Postdoctoral Fellow

David Farmer, Postdoctoral Fellow

Angela Connelly, Research Assistant

Jaspreet Bassi, Research Assistant

Bruce Ngo, PhD Student (co-supervisor Ross Bathgate, FNI)

Alex Wykes, PhD student (co-supervisor Ross Bathgate and Andrew Gundlach, FNI)

Kimberly Thek, PhD Student (co-supervisor, Stuart McDougall, FNI)

Andrew Butler, PhD student (co-supervisor, Stuart McDougall, FNI)

Sarah Ong, Master of Biomedical Science student

Mitchell Wong, Master of Biomedical Science student

Julana Nonis, Master of Biomedical Science student

Anahita Ghanbari, Bachelor of Science (Honours) student

Collaborators

Dr Stuart McDougall, Florey Institute of Neuroscience and Mental Health

Dr Song Yao, Florey Institute of Neuroscience and Mental Health

Professor Ross Bathgate, Florey Institute of Neuroscience and Mental Health

Professor Clive May, Florey Institute of Neuroscience and Mental Health

Professor Matthias Dutschmann, Florey Institute of Neuroscience and Mental Health

Dr Angelina Fong, Department of Physiology, University of Melbourne

Mr Andrew Hammond, Department of Physiology, University of Melbourne

Dr Jaime Foong, Department of Physiology, University of Melbourne

Professor Heather Young, Department of Anatomy and Neuroscience, University of Melbourne

Professor Brian Oldfield, Department of Physiology, Monash University

A/Prof Simon McMullan, Australian School of Advanced Medicine, Macquarie University, NSW

A/Prof Ann Goodchild, Australian School of Advanced Medicine, Macquarie University, NSW

Professor Walter Thomas, School of Biomedical Sciences, University of Queensland, Qld

Professor Ida Llewellyn-Smith, Department of Medicine, Flinders University, SA

Dr Nicola Smith, Victor Chang Cardiac Research Institute, NSW

Dr Rohit Ramchandra, Department of Physiology, University of Auckland, NZ

Professor Julian Paton, Department of Physiology, University of Auckland, NZ

Professor Ivan Dmochowski, University of Pennsylvania, USA

Professor James Eberwine, University of Pennsylvania, USA

Professor Sean Stocker, University of Pittsburgh, USA

Professor Eduardo Colombari, University of Sao Paolo, Brazil

Funding

2017-2019 NHMRC. The brain as a therapeutic target for heart failure. C.N. May, S. Yao, A.M. Allen.

2018-2021 NHMRC. Central neural circuits sub-serving nutrient-activated thermogenesis – the basis of post-prandial energy expenditure. B.J. Oldfield, A.M. Allen.

2019-2022 NHMRC. The vagus nerve and gut-brain interactions: the underpinnings of successful weight loss surgery through recruitment of Brown Adipose Tissue. B.J. Oldfield, A.M. Allen, S.M. McDougall, G. de Lartigue.

2019-2021 NHMRC. Respiratory modulation: Role in the development of cardiovascular diseases. A.M. Allen, S. McMullan, R.D. Bathgate, C. Menuet.

2017-2019 ARC. How the brain regulates blood pressure. A.M. Allen, I. Dmochowski, J. Eberwine, S. Yao.

2017-2019 ARC. Learning to breathe: emerging inhibition of sensory relay mechanisms. M. Dutschmann, S. McDougall, A.M. Allen. NIH (USA)

2016-2020 ARC. Adverse neurogenic actions of dietary salt. PIs - W.B. Farquhar and S.D. Stocker. Co-PI – A.M. Allen FAPESP (Brazil)

2016 ARC. FAPESP Visiting Fellowship. E. Colombari, A.M. Allen

Research Opportunities

This research project is available to PhD, Masters by Research, Honours, Master of Biomedical Science students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.