Quick Project Snapshot
Synaptic gating of viscerosensory signals
The brain receives sensory signals from internal organs that initiate automatic reflexes to adjust their function. We aim to discover the neural pathways that modulate these reflexes that allow optimum organ performance in different circumstances. Defining the fundamental synaptic mechanisms that underlie this information processing by the brain is critical to our understanding of the pathophysiology of cardiovascular and neurological diseases ranging from hypertension through to depression.
Sensory information enables organisms to respond appropriately to changes in environmental and internal conditions. Sensory information is subject to integration and modulation within the brain to enable assignment of salience and relevance. As a consequence, internal organ function can be rapidly reconfigured with a change in behavioral goals – such as during a fight or flight response. Viscerosensory signals, which are the subject of this application, enable the brain to control and coordinate internal organ function via autonomic reflexes. A vital characteristic of autonomic reflexes is that they remain flexible to allow for optimal organ performance under different circumstances. For example, the baroreceptor reflex governs short term blood pressure and operates under different rules at rest as compared to during exercise, stress or disease. How this is achieved is critical to our understanding of the pathophysiology of cardiovascular and neurological diseases.
Modulation of autonomic reflexes is thought to be mediated in the brain stem via hypothalamic and limbic inputs, including those to the solitary tract nucleus. Our hypothesis is that modulation of viscerosensory signals at the level of the solitary tract nucleus underlies autonomic reflex flexibility. To address this, we are combining electrophysiology, a method to record signalling between neurons and across neural networks, with optogenetic tools, which allow selective activation of neurons with light.
Figure. ChR2 activation evokes action potentials in PVN neurons and neurotransmitter release from PVN efferents in the NTS. A. AAV-ChR2-mCherry deposited unilaterally into the PVN resulted in robust mCherry expression. PVN neurons expressing ChR2 fire action potentials in response to LED pulses (10 traces overlaid). B: Activation of ChR2 in PVN efferents in brainstem slices evokes EPSCs in GFP-expressing NTS neurons (40 traces overlaid).
Figure. Amygdala (mCherry) afferents terminate throughout the rostral caudal axis of NTS (arrows) at tyrosine hydroxylase expressing NTS neurons. Scale 20 um.
We study the basic neurophysiology underpinning integration of sensory information within the brain. Our focus of study is at the level of the nucleus of the solitary tract (NTS), a region in the brain that first receives signals from visceral organs including those of the cardiovascular, respiratory and gastro intestinal systems. Knowledge about how the brain and internal organs co-ordinate is pertinent to several disease states, autonomic related; hypertension and obesity and mental health; stress and depression.
Sensory signals concerning internal organ function is termed ‘vicserosensory’, blood pressure for example. We study how the neural network within the NTS is organised; how vicserosensory information modifies behaviour (salt appetite) and visceral organ function during disease (hypertension). Equally, how behaviour (stress/depression) and disease (obesity) modify autonomic reflexes to alter visceral organ function.
The primary techniques utilised within the laboratory revolve around in vitro slice electrophysiology. We possess a large skill-set and toolkit to answer a variety of experimental questions including optogentics, chemogenetics, behavioural paradigms (stress), immunohistochemisty, stereotaxic and other recoverable surgeries that frame our synaptic studies within a larger context.
All Projects by this LabInhibitory mechanisms within the nucleus of the solitary tractSynaptic gating of viscerosensory signalsViscerosensory pathways in the brainUtilising insect peptide hormones in the mammalian nervous systemNext generation vagal nerve stimulation
In Systems Neurophysiology we seek to learn how the nervous system controls various bodily functions and how that control is altered in disease. Our disease focus includes not only neurological disorders such as epilepsy and multiple sclerosis, but also how the nervous system impacts on non-neurological diseases such as heart failure and inflammatory diseases. A clear understanding of basic mechanisms is crucial in developing better therapies and reducing the impacts of illness.