A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second grou ....A decade ago the adult brain was thought of as a structurally-fixed organ. Against this are well-documented cases of slow recovery after massive injuries or stroke. Simple models of brain injury using the tactile, visual and auditory systems of animals as models have now revealed multiple stages of recovery (plasticity). Some of these are inbuilt into the wiring of the neural systems such that functional plasticity can result without the need for any structural or cellular changes. A second group of plastic phenomena depend upon minute changes in the connections between neurons and these are invoked in the first few days following an injury (synaptic plasticity; changes in the pattern and strength of the connections between neurons). Aside from being model systems, there are also parallels of this plasticity with clinical situations such as losses in hearing and sight, and of the adaptations made by the brain in response to prosthetics (e.g. bionic ear) and resorative surgery but the degree of relevance for these situations is unclear. An intriguing aspect of the experiments on auditory and visual systems is that neurons with inputs from both ears, or both eyes, undergo the plastic changes when the relevant sense organ on only one side is damaged but the other is intact. In fact, on the basis of the limited available evidence, it appears that the changes are independent of there being a normal input from the other side. This is difficult to explain in terms of the modern understanding neuronal plasticity at a cellular level. It is thus proposed to study both auditory and visual models of this brain plasticity with stimuli which are systematically varied to extract the extent of bilateral interaction in the induced plasticity. This will enable prediction of how these plasticity mechanisms will be involved in adaptations made to prosthetics and surgical corrections.Read moreRead less
A New Map Of The Human Cerebral Cortex To Assist The Interpretation Of FMRI And PET Studies
Funder
National Health and Medical Research Council
Funding Amount
$264,307.00
Summary
The cortex is the brain structure most intimately involved in cognition, motivation and emotion. It is thought to be the principal area affected in diseases such as schizophrenia, and Alzheimer's disease. An enormous and costly effort is expended in functional neuroimaging with PET and fMRI to establish the relation between cortical regions and neurologic and psychiatric dysfunction. Unfortunately due to the unavailability of an accurate map of the human cortex, the researcher is left only with ....The cortex is the brain structure most intimately involved in cognition, motivation and emotion. It is thought to be the principal area affected in diseases such as schizophrenia, and Alzheimer's disease. An enormous and costly effort is expended in functional neuroimaging with PET and fMRI to establish the relation between cortical regions and neurologic and psychiatric dysfunction. Unfortunately due to the unavailability of an accurate map of the human cortex, the researcher is left only with crude estimates of the location of normal and abnormal cortical activity. Further, there is limited ability to relate the human data to the wealth of knowledge available on non-human primate brains. Conversely, researchers using animal models of human cortical pathology cannot readily relate their data to humans because the similarities between the brains of experimental animals and humans have not yet been comprehensively established. The present project will establish the similarities between the cortex of humans and rhesus monkeys. By revealing comprehensively the location of cortical areas this project will provide the context within which hypotheses of cortical function and dysfunction can be tested. The applicants were the first to use the distribution of chemical substances in the brain to construct a comprehensive map of the rat brain. This work is the only Australian publication ranked amongst the 50 most cited items in the history of science. They wish to apply similar techniques to study the least understood part of the human brain, the cortex. The research proposed herein will not examine human tissue from individuals who suffered from depression, anxiety, schizophrenia, Alzheimer's disease, or Parkinson's disease. However, the outcomes of the proposed research will be of assistance to virtually everyone who studies the relation between these diseases and the brain.Read moreRead less
Genetic Cues Responsible For Interneuron Migration And Layering In The Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$650,250.00
Summary
Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in ....Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in sufficient numbers, or impediments to neuron migration to proper destinations are certain recipes for neurological disorders, including epilepsy and mental retardation. In this application, we will study how neurons are assembled in the cortex. We will focus on a subpopulation known as interneurons that are vital for toning down electrical discharges from excitatory neurons. We will investigate how these neurons are able to migrate long distances to settle into defined layers of the cortex. Mutant mice with deleted genes have a defect in this process and the aim of this project will be to study the precise mode of action for some of these genes.Read moreRead less
Mechanisms Controlling Interneuron Migration And Layering In The Cortex
Funder
National Health and Medical Research Council
Funding Amount
$613,060.00
Summary
This work will increase our understanding of how the brain is assembled and what mechanisms control this process. Understanding this highly orchestrated string of events is vital as abnormal positioning and numbers of neurons are known pathologies in brains of patients with epilepsy and schizophrenia. Using state of the art equipment we can visualize neurons moving in brain slices in real-time and investigate environmental factors involved in this important process.
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less
Developmental Plasticity In The Nonhuman Primate Visual Cortex
Funder
National Health and Medical Research Council
Funding Amount
$464,417.00
Summary
A phenomenon that has puzzled many for a number of years is why damage to the visual brain during infancy has far less of an impact on visual capacity than the same lesion suffered later in life. This project hopes to uncover this mystery and see how brain 'wiring' is altered to compensate.