Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
Interaction Of TRP Channels And Inflammatory Mediators: A Critical Role In Visceral Pain
Funder
National Health and Medical Research Council
Funding Amount
$308,747.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we feel, such as touch and pain. The function of these channels can be altered by substances released by the body during inflammation. Some TRP channels have specialized roles in signalling pain from the colon which can be enhanced during colonic inflammation. Understanding how TRP channels and inflammatory mediators function and interact is essential if we are to find treatments for colonic pain.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Extraction Of Key Features Of Natural Speech By Ventral Cochlear Nucleus Neurons
Funder
National Health and Medical Research Council
Funding Amount
$225,330.00
Summary
Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station i ....Little is known about how speech is processed and transformed by the central auditory pathway, and how the critical temporal and spectral features that identify a speech sound segment (a phoneme) are extracted. To date, most studies have approached this issue by using synthetic speech and examined the responses of the peripheral auditory nerve only. The aim of this study is to examine how important features of naturally-spoken speech are encoded by the cochlear nucleus (CN) - the first station in the auditory pathway located in the brainstem. The CN is a complex of different cell types that have the capacity to transmit, transform, and encode complex acoustic information in different ways. The proposed experiments involve recording the bioelectrical signal from single CN cells in anaesthetised rats while presenting naturally-spoken syllables, both in quiet and in the presence of noise. It is important to examine what happens to the neural responses in the latter condition, because all animals must cope with the problem of extracting important signals from background noise. While noise clearly interferes with the perception of another sound, the auditory system is in fact quite good at extracting signals in the presence of noise. This is well demonstrated by our ability to understand speech in the presence of quite high noise levels. This ability is severely degraded in the hearing impaired. Thus, one of the aims of this study is to examine the mechanisms and limits of the CN's ability to encode speech in a noisy background. A greater understanding of the mechanisms the nervous system uses to extract critical features of speech will not only build on our knowledge of auditory brainstem processes, but may also provide clues to improving processing strategies for cochlear implants.Read moreRead less
Improved Perception Of Temporal Information In Electrical Signals For Profoundly Deaf Users Of Cochlear Implants
Funder
National Health and Medical Research Council
Funding Amount
$170,440.00
Summary
The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulati ....The ultimate goal of this project is to improve the ability of cochlear implant users to understand speech. The way in which a speech signal varies in amplitude over time provides useful information to the listener about the content of the speech signal. Currently, the way that the acoustic signal amplitude is converted to electrical signal amplitude for cochlear implantees does not take into consideration the very significant loudness summation present in multiple-electrode electrical stimulation. That is, when there are multiple sequential current pulses on different electrodes over a short time, the resultant loudness is greater than the loudness due to individual current pulses. The lack of consideration of loudness summation effects has led to the amplitude variations in the acoustic signal not being accurately represented in the loudness variation perceived by the cochlear implantee. This project aims to develop a practical way of more accurately representing speech signal amplitude fluctuations for cochlear implantees by studying the effects of loudness summation. A second aim of the project is to study the effects on perception of using differently-shaped current pulses from those currently used. There is evidence from physiology experiments that using different shapes might cause the electrical stimulation to activate a more narrowly-spaced set of auditory neurons for each electrode. The application of results of both these studies will lead directly to improved perception of speech and other sounds by cochlear implantees, thus improving their communication ability and quality of life.Read moreRead less
Cortical Interactions Of Parallel Afferent Channels Underlying Visual Perception, Attention And Memory
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
The visual pathways from the eyes to the brain consist of distinct groups of cells which are specialised to signal different aspects of the visual scene such as colour, contrast and movement. As the information they carry is relayed through and processed in many different regions of the brain these parallel information channels were, until recently, believed to remain completely separate from each other. Furthermore, it had been proposed that as the information reaches the visual neocortex the i ....The visual pathways from the eyes to the brain consist of distinct groups of cells which are specialised to signal different aspects of the visual scene such as colour, contrast and movement. As the information they carry is relayed through and processed in many different regions of the brain these parallel information channels were, until recently, believed to remain completely separate from each other. Furthermore, it had been proposed that as the information reaches the visual neocortex the information is channeled through two main largely parallel information processing streams, a dorsal stream to the parietal cortex (a where system) and a ventral stream to the temporal cortex (a what system). However, our recent functional studies (and anatomical studies from other laboratories) have indicated that the different information channels do interact already at a relatively early level of the visual pathway, namely in the primary visual cortex. We have shown this in two ways: (1) there is convergence of different information channels on individual neurones in the primary visual cortex; (2) signals from the faster where pathway comes back to the primary visual cortex to gate the slower channels going into the ventral what pathway. We have seen this occur in an attention paradigm and in a memory task. We will explore these interactions further to test hypotheses about: (1) how the convergence of different information channels relate to the functional and anatomical architecture of the visual cortex; (2) investigate at length the most poorly understood, the so-called koniocellular pathway from the retina to the cortex. This pathway seems to contain a specialised component which carries information about blue objects; (3) identify the source of the spotlight of attention we have discovered and (4) how and from where early visual structures receive the gating inputs in certain memory tasks.Read moreRead less
Cortical Interactions Between Afferent Channels In Macaque Visual System
Funder
National Health and Medical Research Council
Funding Amount
$380,154.00
Summary
There are three distinct groups of cells that carry the visual information from the eyes to the brain, each pathway signaling a different aspect of the visual scene. This project will study in detail the lesser known of these three pathways (koniocellular neurones): what sort of information they carry into the brain, how it is combined with the other pathways to yield our composite picture and where in the brain such combination takes place.
Effects Of Saccadic Eye Movements On Perception And Visual Memory.
Funder
National Health and Medical Research Council
Funding Amount
$255,750.00
Summary
We all make rapid eye movements, called saccades, three times a second all our waking lives. They allow us to direct our gaze at what catches our attention, but they sweep images across our retinas and alter all the linkages between the eyes and the brain. The question at the heart of this project is how the visual system maintains perceptual stability given the disruption to the flow of visual input that saccades necessarily cause. It has to do more than suppress disturbing signals; it has to l ....We all make rapid eye movements, called saccades, three times a second all our waking lives. They allow us to direct our gaze at what catches our attention, but they sweep images across our retinas and alter all the linkages between the eyes and the brain. The question at the heart of this project is how the visual system maintains perceptual stability given the disruption to the flow of visual input that saccades necessarily cause. It has to do more than suppress disturbing signals; it has to link the present with the past. In recent years we and others have made substantial progress toward answering this question. In this project we plan a four-pronged attack that will take us further. We anticipate that our results will reveal how the visual system maintains and adjusts its representations of space and time, integrates signals from before and after saccades, and regulates the flow of information from memory to achieve a seamless melding of the present with the past. This project is not directed at any particular clinical problem, but disturbances of perception and memory are aspects of many clinical conditions. If we succeed in our aims what we discover will constitute a major scientific discovery which should find application to many conditions in which perception and memory are disturbed, from dyslexia to brain damage and even affective disorders such as schizophrenia and depression.Read moreRead less