Synaptic Transmission In The Mammalian Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$460,500.00
Summary
In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. Th ....In order to properly understand the complex functions of the brain and the abnormalities underlying neurological disorders, we must understand how individual neurons communicate with each other. Communication occurs at specialized contacts, or synapses. An individual neuron may receive tens of thousands of synaptic contacts from hundreds or thousands of other neurons. Despite intensive investigation, the processes which regulate synaptic strength between central neurons are poorly understood. The overall aim of this proposal is to understand the basic mechanisms underlying synaptic transmission at excitatory and inhibitory synaptic connections in the mammalian brain. We will investigate specific synaptic connections in the central pathways of the auditory system, because our previous studies have demonstrated a number of key technical advantages in studying these synapses. We will use electrophysiological recording from synaptic terminals and neurons in isolated living slices of the brainstem of mice. We will use imaging techniques and electron-microscopy to examine the structural details of synaptic connections, as structure is thought to play a major role in determining the strength of synaptic transmission. We will also study the structural and functional properties of auditory synaptic connections in congenitally deaf animals. Our recent study comparing normal and congenitally deaf mice has already revealed significant differences. Our results will provide important insights in the regulation of synaptic strength in the central nervous system, and into the regulation of synaptic transmission at central synapses which have developed under conditions of abnormal sensory activation.Read moreRead less
Plasticity In The Thalamic Reticular Nucleus During Normal And Altered Postnatal Development
Funder
National Health and Medical Research Council
Funding Amount
$392,036.00
Summary
Thalamic centres concerned with vision send information through the thalamic reticular nucleus to multiple cortical areas in which different aspects of the visual world are analysed. These cortical areas in turn send connections back through the reticular nucleus to the thalamus. Cortical function ultimately depends on the correct connections being established between the sensory receptors and the thalamus and between the thalamus and cortex. Far from being merely a relay station of peripheral s ....Thalamic centres concerned with vision send information through the thalamic reticular nucleus to multiple cortical areas in which different aspects of the visual world are analysed. These cortical areas in turn send connections back through the reticular nucleus to the thalamus. Cortical function ultimately depends on the correct connections being established between the sensory receptors and the thalamus and between the thalamus and cortex. Far from being merely a relay station of peripheral sensory information the dorsal thalamus modifies and interacts with the flow of information around the brain. The reticular nucleus forms an integral part of this information flow. How these connections develop and are modified by disturbance to the visual pathway is crucial to our understanding of brain function. To this end, we will study the connections between three areas of the brain concerned with vision, the thalamic reticular nucleus, the thalamus and the visual cortices. We will focus our study on the development of the reticular nucleus and the importance of a normal visual environment in establishing the proper connections between different brain areas. The importance of studying normal and abnormal development is that it can provide a description of the kinds of experience leading to specific types of neural abnormalites. This information tells us the degree to which connections are malleable and is of potential clinical importance.Read moreRead less
Organization Of Descending Auditory Projections From Inferior Colliculus To Cochlear Nucleus
Funder
National Health and Medical Research Council
Funding Amount
$473,121.00
Summary
Sensory information gains awareness by ascending brain pathways to reach consciousness. Descending projections, however, have grown in importance because of implications for feedback management of ascending signals. Studies of these pathways will provide insight into auditory processing with respect to selective volume control, calibration adjustments between the two ears, and the extraction of signals from background noise. The data could lead to new strategies for treating hearing disorders.
Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will ....Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will attempt, for the first time, to define the location in the cerebral cortex of the drive to ingest water (perception of thirst).Read moreRead less
Interaction Of Thalamic And Cortical Activity In The Primate Visual System
Funder
National Health and Medical Research Council
Funding Amount
$487,580.00
Summary
We recently discovered that a primitive part of the visual pathway shows rhythmic nerve cell activity similar to slow brain waves recorded in sleep, anaesthesia, and epilepsy. We now plan to discover whether these primitive cells help to generate brain waves by measuring the timing of their activity together with brain waves in different visual and non-visual parts of the brain. This project will contribute to understanding the role of brain waves in normal brain function and epilepsy.
Neural Circuits For Residual Vision After Damage To Striate Cortex
Funder
National Health and Medical Research Council
Funding Amount
$662,220.00
Summary
Brain cells have the ability to rearrange their connections to create alternate pathways, which compensate for loss of function following brain damage. To understand why some people become blind after damage to the visual cortex, and some don't, we will determine how neural connections change following lesions in different stages of life. The project will provide important information that may allow future development of treatments for blindness due to stroke or traumatic brain injury.
Dissecting The Central Organisation Of Cough Neural Networks
Funder
National Health and Medical Research Council
Funding Amount
$880,928.00
Summary
Cough is the most prevalent symptom of lung disease and the most common reason for people to seek medical advice. However, cough neural processes are poorly defined and as a result current cough therapies are largely ineffective making cough a significant unmet clinical problem. This project will novel viral strategies to dissect and manipulate cough neural pathways in the brain, providing insights into the neural processing of airway sensations and coughing.
Innate Threat Detection Circuits In The Superior Colliculus Co-ordinate Respiratory And Cardiovascular Responses To Visual Stimuli
Funder
National Health and Medical Research Council
Funding Amount
$517,958.00
Summary
Our surroundings affect our bodies: light pollution, traffic, and aircraft noise all significantly affect cardiovascular health. This project will investigate interactions between brain systems that subconsciously scan our surroundings for interesting or threatening features, and those that co-ordinate the cardiovascular and respiratory systems. We will generate new knowledge that describes how the brain detects danger and translates this into signals that contribute to cardiovascular risk.
Investigations Of Mechanisms Underlying Autonomic Cardiovascular Regulation In Medial Temporal Lobe Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
People with epilepsy often show disturbed cardiovascular function which may increase mortality risk. This may reflect seizure related disturbances in the autonomic circuitry regulation of the cardiovascular system. We apply advanced brain imaging analysis of altered neural structure, circuit connectivity and function within medial temporal lobe and mid brain, combined with clinical assessment of autonomic function to provide important new insights into cardiac disturbances in epilepsy.
Role Of Cortico-cortical Connections In Mediating Cerebral Cortex Plasticity: Visual Cortex Model
Funder
National Health and Medical Research Council
Funding Amount
$362,500.00
Summary
In mammals injury to the retina not only affects the neurones within the eye but also induces changes in the other parts of the brain, particularly in the visual cortex. It has been found that after retinal injury cells in the visual cortex, normally receiving an input from the injured part of the retina, now receive an input from adjacent normal retina ( ectopic receptive field ). All mammals with well developed vision have a large number of separate visual cortical areas (more than 30 in prima ....In mammals injury to the retina not only affects the neurones within the eye but also induces changes in the other parts of the brain, particularly in the visual cortex. It has been found that after retinal injury cells in the visual cortex, normally receiving an input from the injured part of the retina, now receive an input from adjacent normal retina ( ectopic receptive field ). All mammals with well developed vision have a large number of separate visual cortical areas (more than 30 in primates). These areas are arranged in a hierarchy in which it is thought that as features of the visual stimuli become more complex they are discriminated in the areas higher in the hierarchy. These higher-order areas also project back to lower-order areas. This feedback activity from the higher areas can be reversibly abolished by cooling a given area to about 10oC and then rewarming it back to its normal temperature. We will try to determine if in cats (animals with well developed vision) following damage to a small region of the retina the feedback activity from higher visual cortical areas affects the ectopic receptive fields in the lower visual cortical areas. Another possibility is that the ectopic receptive field apparent following retinal damage might depend on horizontal connections within the particular cortical area, running from normal cortex to the area of cortex affected by the lesion. We propose to test this idea by blocking reversibly (with chemical agents) transmission of these horizontal fibres and determining the characteristics of neurones in the area affected by the lesion. Understanding the role of feedback and horizontal cortico-cortical connections in establishing new ectopic receptive fields following spatially delineated damage to the retina will help us to understand the mechanisms underlying perceptual distortions and visual hallucinations which occur following retinal traumas or some age-related retinal degenerations.Read moreRead less