Use Of A Novel Technique To Identify The Sensory Nerve Endings That Respond To Painful Stimuli In The Upper Gastrointestinal Tract And Characterize Their Mechanisms Of Activation
Funder
National Health and Medical Research Council
Funding Amount
$353,243.00
Summary
Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characte ....Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characterise the mechanisms underlying their activation.Read moreRead less
Understanding How Inflammatory Bowel Disease Causes Hypersensitivity Of Colonic Sensory Nerve Endings And Increased Abdominal Pain
Funder
National Health and Medical Research Council
Funding Amount
$589,466.00
Summary
Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inf ....Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inflammation to cause increased abdominal pain.Read moreRead less
Importance Of CGRP Alpha In Pain Processing From The Large Intestine
Funder
National Health and Medical Research Council
Funding Amount
$548,289.00
Summary
This project will determine the mechanisms by which sensory nerve endings detect painful stimuli in the large intestine. The project will use a novel genetically modified mouse (that is only available in our laboratory) which allows us, for the first time, to visualize and record directly from the sensory nerve endings that detect painful stimuli and work out how this process occurs. We also identify a specific gene that is essential for detecting painful stimuli from this organ.
A Novel Technique For Prolonged Silencing Of Visceral Pain Without Opiates
Funder
National Health and Medical Research Council
Funding Amount
$637,383.00
Summary
There has been substantial interest in the community for pain relief without opiates. This project demonstrates a new strategy to suppress pain at the source for prolonged periods, by suppressing activity in the sensory nerve endings that detect pain, not by acting in central pathways like opiates. To do this, we use a harmless virus to shut down a vital sodium channel for pain perception. These experiments use techniques that were recently developed in our lab and cant be performed elsewhere.
Mechanisms Of Activation Of Vascular Afferent Nociceptors To The Gut
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
We have recently identified the nerve fibres responsible for detecting pain from the gut. In this project we will study exactly how these nerve cells are activated by movements of the gut wall, by changes in blood vessel diameter and how this can be studied most efficiently We will use this information to develop simple preparations in which to study these sensory nerves in animal and adult tissue to test which drugs may affect their excitability and hence be useful in treating gut pain.
Signals And Noise: A Study Of The Neurocognitive Mechanisms Underpinning Habituation To Noise In Normal And Damaged Hearing
Funder
National Health and Medical Research Council
Funding Amount
$408,938.00
Summary
McLachlan and Wilson recently published the first model of hearing that combines brain structure with function. This model postulates that recognition mechanisms initiate first, and then regulate the processing of other features. This project will investigate whether recognition mechanisms enable the auditory system to adapt to repetitive (background) noise by predicting and inhibiting responses to these sounds, and any changes in these mechanisms that may accompany hearing damage and tinnitus.
The Role Of Corticothalamic Feedback On The Response Dynamics Of Thalamic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
A fundamental question in neuroscience is how the brain selectively processes sensory information to generate a reliable representation of the world. Positioned in the centre of the brain, the thalamus plays a key role in sensory processing. This project investigates how the interaction between thalamus and cortex shapes the selection and gating of sensory information. This is a fundamental question in basic neuroscience with the potential to increase our knowledge about attentional deficits.
The Role Of Dopamine And Other Neuromodulators As Light Signals In The Inner Retina: A Link To Night Blindness Disorders
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-ligh ....Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.Read moreRead less
Cochlear Type II Neurons In Contralateral Suppression
Funder
National Health and Medical Research Council
Funding Amount
$459,434.00
Summary
Sound in one ear affects hearing in the other ear. This contralateral suppression is important for hearing attention and protection from noise damage. We will test the hypothesis that cochlear type II sensory neurons provide the sensory input for this process using models where neuronal development is altered, or the neurons are removed. The study addresses hearing disability in society, facilitating cochlear prosthesis development and the understanding of hearing loss.