Dr Subramanian completed his PhD in Systems Neurophysiology at the University of Sydney on a National Health and Medical Research Council (NHMRC) scholarship. He has since held a postdoctoral fellowship at the Nobel Institute for Neurophysiology (Sten Grillner’s laboratory), Karolinska Institutet, Stockholm and an Assistant Professorship at the University of Groningen, the Netherlands. Dr Subramanian currently holds a Senior Research Fellowship at the Asia-Pacific Centre for Neuromodulation (APCN), Queensland Brain Institute (QBI). In this position he heads the Motor and Autonomic Control Systems laboratory with a focus on the neurophysiology and functional neuroanatomy of midbrain periaqueductal gray (PAG) and its translational neuromodulation for treatment of neurogenic autonomic disorders (respiratory, cardiovascular and urinary). Dr Subramanian has pioneered the systems neuroscience of the midbrain periaqueductal gray (PAG) circuit and has published several seminal papers in top neuroscience journals. He has edited two thematic books on PAG and brainstem homeostatic control mechanisms for the prestigious journal Progress in Brain Research. He has several invited national and international lectures, editorials, awards, prizes and recognitions to his credit. He is also a recipient of research grant funding >$2.4 million (project & infrastructure grants and fellowships) from various national and international agencies. Dr Subramanian currently holds a Teaching Internship at the UQ School of Biomedical Sciences.
The midbrain periaqueductal gray (PAG) integration of emotional expression
The PAG laboratory focusses on a particular area surrounding the midbrain aqueduct, known as the periaqueductal gray (PAG), which acts as a critical interface between the limbic and the autonomic brain. Modulation of the autonomic nervous system is a pre- requisite for survival of the individual and of the species. For example, respiration has to be adjusted in case of speech, strenuous exercise, laughing or crying. Cardiovascular system has to be adjusted for sudden escape from danger, expression of fear or defense reaction. Autonomic
centers in pons and medulla regulate basic homeostasis to maintain body metabolism, but they cannot modulate the autonomic tone in the context of survival challenge (i.e. mediating environmental danger) and/or emotional expression (laughing, crying, singing), for which they need input from higher brain centers. In simple terms, the PAG functions as the higher brain center to generate the final motor and autonomic output for mediating survival challenge and/or emotional expression. Lesioning the PAG renders the animal (and human) mute and akinetic. Animals (and humans) thus become incapable of expressing emotional behavior except basic autonomic regulation. The PAG is well situated at the crossroads of ascending sensory information and inputs from higher centers that modulate limbic-autonomic processes for mediating survival challenge and/or emotional expression.
Functional autonomic topography in the PAG
The motor organization of positive and negative emotional vocal expressions are segregated in the PAG
PAG modulates the activity of respiratory cells in the caudal medulla during emotional expression
PAG uses the NRA as a tool to gain access to the motoneurons for generating expulsive behaviour.
One project in the laboratory examines the properties of cells, neurotransmitters and receptors in the PAG. A second project is focused on investigating limbic commands to the PAG. Principle pathways examined include the amygdala-PAG, the hippocampus-PAG, and the anterior cingulate cortex (ACC)-PAG circuit interactions. A third project examines the output side of the PAG to various brainstem autonomic centers.
Emotions studied include fear, anxiety and vocalization, while autonomic systems investigated include breathing, cardiovascular system and micturition.
The laboratory uses a variety of in vivo electrophysiology techniques including decerebrate and anesthetized animal preparations, stereotaxic chemical mapping of microcircuits, single & multi unit cell recording, anatomical reconstruction, axonal tract-tracing, fixed brain tissue imaging, immunohistochemistry and pharmacology to unravel the PAG circuit function.
The lab combines the study of brain circuit dynamics with autonomic system via simultaneously investigating nerve and muscle (EMG) function during PAG –induced specific emotional or survival behaviors.
Recently the laboratory has established telemetric and optogenetic platform and behavioral paradigm for examining the PAG circuit function in freely moving animals.
DBS Neuromodulation of brainstem circuits in animal models in vivo
The laboratory has also established a cutting-edge DBS platform in vivo for investigating the effect of combined electrical and optical neuromodulation of the PAG on autonomic control mechanisms in animal models of health and disease.
- Professor Peter Silburn – UQ, DBS Neurologist
- Professor Gert Holstege – Professor Emeritus, University of Groningen, The Netherlands, APCN Honorary Affiliate
- Dr Surya Singh – ITEEE, UQ
Subramanian HH, Arun M, Silburn PA and Holstege G (2015). Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray. Journal of Comparative Neurology: In press. DOI: 10.1002/cne.23869, [Epub ahead of print]
Holstege G and Subramanian HH (2015). Two different motor systems generate human speech.. Journal of Comparative Neurology: In press. doi: 10.1002/cne.23898. [Epub ahead of print]. Figure selected for cover print of the journal edition
Subramanian HH and Holstege G (2014). The midbrain periaqueductal gray changes the eupneic respiratory rhythm into a breathing pattern necessary for survival of the individual and of the species. Progress in Brain Res. 212:352-384.
Subramanian HH and Holstege G (2013). Stimulation of the midbrain periaqueductal gray modulates pre-inspiratory neurons in the ventrolateral medulla in the in vivo rat. Journal of Comparative Neurology: 521(13):3083-98.
Subramanian HH (2013). Descending control of the respiratory neuronal network by the midbrain periaqueductal grey in the rat in vivo. Journal of Physiology, 591:109-22. (cited by Faculty of 1000 Biology: http://f1000.com/prime/717967820#eval793467507)
Subramanian HH and Holstege G (2011). The midbrain and medullary control of post- inspiratory activity of the crural and costal diaphragm in vivo. Journal of Neurophysiology. 105(6): 2852-62.
Hilaire G, Voituron N, Menuet C, Ichiyama RM, Subramanian HH and Dutschmann M (2010). The role of serotonin in respiratory function and dysfunction. Respiration Physiology & Neurobiology, 174(1-2): 76-88.
Subramanian HH and Holstege G (2009). The nucleus retroambiguus control of respiration. Journal of Neuroscience, 29(12): 3824-32.
Subramanian HH, Balnave RJ and Holstege G (2008). The midbrain periaqueductal gray control of respiration. Journal of Neuroscience, 28(47):12274-12283. (cited by Faculty of 1000 Biology: http://www.f1000biology.com/article/id/1141935/evaluation).
Casual Research Assistant
Kieran Gossage (Research Intern)
Michael Wong (Research Intern)
Kwee Lee (Research Intern)
You can conduct the following research degrees at APCN's neurophysiology laboratory:
• Summer/Winter Research Program
• Master of Philosophy (MPhil)
• Doctor of Philosophy (PhD)
APCN/QBI will provide you with support to apply for these research programs and relevant scholarships, including the Australian Postgraduate Award and a UQ Research Scholarship.