Quick Project Snapshot
Viscerosensory pathways in the brain
Viscerosensory information which reports internal organ function is broadcast throughout brain. This project seeks to define how viscerosensory neural pathways are organised within the brain. This basic knowledge will form the basis for understanding how the brain coordinates internal organ function during everyday occurrences such as exercise or during stress. It also creates a framework for future research into autonomic related disease such as hypertension.
There is a class of sensory information that is generally not perceived but is vital to maintaining life, called viscerosensory information. These signals come from neurons embedded among internal organs and report their function. All studies to date organise viscerosensory input to the brain by afferent functional class, called “input organization.” Another perspective is to discover how viscerosensory afferent input is arranged by defining were the signals are sent to within the brain, or “output organisation.”
This gap in our knowledge means we do not grasp how internal organ function is regulated through the course of normal variations in everyday life; whether it be modulation of respiratory rhythm during exercise, during stress or the integration of endocrine signals with autonomic function. Viscerosensory afferent axons enter the brain and terminate at the solitary tract nucleus.
A major push in neuroscience is to define the connectome, a map of every synaptic connection in the brain. This project seeks to define the synaptic connections to specific solitary tract nucleus output neurons. To address this idea I propose combining two powerful techniques: in vitro slice electrophysiology with neuronal tracing.
Figure. Identification of direct and indirect pathways to NTS-amygdala (AMY) projecting neurons. A. A NTS-AMY neuron (& recording electrode) under dodt contrast (upper) and fluorescence (lower) within the NTS. B. Upper traces; increasing shock (arrows) intensities at the solitary tract (ST) evoked two distinct groups of EPSCs. Each group exhibited distinct activation thresholds, EPSC amplitudes, latency, low jitter and zero failure rates. These data are consistent with the recruitment of two unique primary afferents to this 2nd order NTS-AMY projecting neuron (C. left). B. Lower traces; increasing shock (arrows) intensities evoked two distinct groups of EPSCs. Each group exhibited distinct activation thresholds. However, frequent failures (no response after ST shock) are observed and EPSC latency varied (high synaptic jitter). These data are consistent with the recruitment of two unique primary afferents axons that connect this NTS-AMY neuron via polysynaptic pathways (C. right). Scale bars for images = 20 um. For traces x-axis scale bars = 2 ms, y-axis = 50 pA.
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.