Role Of Dendritic Information Processing In Visual Circuit Computations
Funder
National Health and Medical Research Council
Funding Amount
$895,244.00
Summary
Vision is the primary sensory modality in man, and its disturbance carries an enormous socio-economic burden. The dynamic operations of the neuronal assemblies that underlie vision are poorly understood, partly because of an incomplete description of the computational properties of visual neuronal circuits. The aims of the application are to mechanistically dissect defined computational operations of visual neural circuits using advanced electrophysiological and optical recording techniques.
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
Mechanisms Underlying Efferent Feedback In The Vestibular System
Funder
National Health and Medical Research Council
Funding Amount
$491,475.00
Summary
The balance system has a remarkable, but poorly understood capacity for self-repair. An intrinsic feedback mechanism, the Efferent Vestibular System or EVS is thought to play a major role in this self-repair. Surprisingly, we know little about EVS function in animals or humans. We will study the EVS in mice and humans to gain a better understanding of how it works. This information will then drive the design of therapies that improve and restore balance in disease, injury, or ageing.
Synaptic Environment Of Nociceptive Inputs To The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$499,860.00
Summary
Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has resolved. This ongoing pain often is resistant to alleviation by c ....Pain affects everyone at some stage in their life. Usually, the pain subsides by itself as the underlying cause is resolved. Thus, the damaged tissue heals or we move away from a potentially injurious stimulus and we become free of pain. However, pain can persist for two main reasons: the underlying cause cannot be treated adequately and the painful stimulus continues; or the pain is maintained long after the primary stimulus has resolved. This ongoing pain often is resistant to alleviation by common analgesics. Therefore, a major aim of the pharmaceutical industry is the development of new drugs to target persistent pain. This requires a thorough understanding of how the nerves that detect painful stimuli transmit that information into the spinal cord, and then on to the brain, where we construct a conscious perception of the pain. Various kinds of painful stimuli, such as tissue damage, noxious chemicals, or extreme temperatures, are detected by different types of nerves. Each nerve type can be identified by its characteristic chemical profile. Recently, we found that some of these nerves probably do not transmit their messages to the spinal cord in the way everyone had thought. This means that there must be an alternative way for many types of painful stimuli to be transmitted into the spinal cord. In this project, we will use a sophisticated suite of modern microscopic and electrical recording techniques to find out what this alternative mechanism is. Our central idea is that most types of painful stimuli simultaneously activate two types of sensory nerves. These nerves then connect with specific nerve cells in the spinal cord before painful information is relayed to the brain. Our proposal suggests a new mechanism for understanding how pain can develop from being an acute defensive reaction to a chronic problem. In turn, this should lead to improved strategies for developing and testing new analgesic drugs.Read moreRead less
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
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Dizziness, vertigo, and imbalance affect nearly half the population by the age of 60 and balance-related falls, especially in the elderly, are a serious health concern. Surveys of primary care doctors have shown that dizziness and vertigo are as prevalent as hypertension and angina, and approximately 40% of the population experience dizziness severe enough to seek medical attention. Unfortunately, most symptoms are not relieved by currently available medical treatment. There is, however, a remar ....Dizziness, vertigo, and imbalance affect nearly half the population by the age of 60 and balance-related falls, especially in the elderly, are a serious health concern. Surveys of primary care doctors have shown that dizziness and vertigo are as prevalent as hypertension and angina, and approximately 40% of the population experience dizziness severe enough to seek medical attention. Unfortunately, most symptoms are not relieved by currently available medical treatment. There is, however, a remarkable hidden reserve of 'self-repair' in the balance system that can be triggered under certain conditions. We call this process 'vestibular compensation' and if we can understand those conditions and discover the means by which this reserve affects the nervous system, we may be able harness its power to alleviate the all distressing symptoms of imbalance. Perhaps we may even be able to apply these principles to other critical systems that may need repair. We propose to look at a key region in the central nervous system that is responsible for processing balance signals and may be very important in 'vestibular compensation'. We will try to activate this recovery process under controlled conditions so that we can understand the changes that occur. Specifically we will examine the role of vestibular (balance) neurons in the central nervous system that appear to be modified following trauma of the inner ear balance organs. We will use our new recording techniques to examine these vestibular neurons to see how their intrinsic properties may change and what external or internal factors influences this change. Our aim is to understand what factors promote and what factors inhibit full recovery.Read moreRead less
Determining The Mechanisms Underlying Chronic Visceral Pain And Providing Novel Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Gastroenteritis activates special types of nerve endings in the gut to cause acute pain. In chronic gut pain, although the damaged tissue has healed, the nerve endings remain active and don’t reset back to normal. This project will identify why this occurs, determining pain mechanisms associated with Irritable Bowel Syndrome, a leading form of chronic pain. It will identify which ion channels and receptors can be targeted allowing the development of novel and effective therapies for pain relief.
Development Of Peripheral Sensory Pathways In Humans
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
To receive the appropriate information about the state of our muscles, joints, organs, and skin we need a properly 'connected' sensory system. Recent evidence suggests traumatic events during early development can alter sensory connections within the spinal cord. This can lead to debilitating movement disorders, digestive diseases, and increased pain. In this study we will examine how peripheral sensory fibres connect with the appropriate nerve cells in the human spinal cord during development.