Thalamic And Basal Forebrain Contributions To Auditory Cortical Reorganization Produced By Partial Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$364,768.00
Summary
When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, ....When part of the cochlea is damaged in adult animals, leading to a partial hearing loss, the auditory area of the cerebral cortex reorganizes itself, so that the area deprived of input by the peripheral lesion is not silent, but is occupied by expanded representations of adjacent frequencies. This reorganization has been observed in a number of species, including non-human primates, and it seems likely that it also occurs in humans with cochlear damage and hearing loss of this sort. If it does, it would have important consequences for the way in which input from a hearing aid or cochlear prosthesis (bionic ear) is processed in the brain. This Project is designed to clarify the nature of the systems in the brain that contribute to this form of cortical plasticity, using an animal model. One aim is to determine whether the plasticity is intrinsic to the cortex or occurs in the pathways over which information is conveyed to the cortex. This will be assessed by determining whether such plasticity is also found in the auditory thalamus, the final subcortical auditory nucleus from which information is sent to the cortex. The second aim is to determine whether the occurrence of plasticity is controlled by modulatory influences from the basal part of the forebrain. Neurons in this area project to many parts of the cortex, and evidence from other sensory systems suggests that these projections exert a permissive function, allowing the cortex to reorganize when input is altered. This aim will be pursued by determining whether cortical reorganization occurs after hearing loss when this basal forebrain system is inactivated. The significance of these studies is that they will elucidate the way in which the brain reorganizes itself when it is confronted with altered input. This information is important for our understanding of normal auditory information processing mechanisms and of the way in which input from prosthetic devices is processed in the hearing-impaired.Read moreRead less
Amelioration Of The Cognitive Deficits In A Model Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
The project investigates a brain molecule called p75, and the part it plays inmemory impairment in Alzheimer's Disease (AD). We predict that p75 is a vital link in the disease processes affecting memory.This research has the potential to lead to an effective treatment for AD, by stimulating work on compounds with the ability to blockthe damaging functions of p75.
The Embryological And Molecular Basis Of Zic2 Involvement In Holoprosencephaly
Funder
National Health and Medical Research Council
Funding Amount
$624,145.00
Summary
The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language ....The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language development, seizures, and obvious facial abnormalities. In its most severe form only one eye develops in the middle of the face, a condition known as cyclopia and a large majority of the severely affected children will die late in gestation or at birth. This condition can be inherited, but because the genetic lesions that cause this problem affect different people differently, people can carry the causative genetic change(s) without knowing it. We need to identify and study the genetic lesions that contribute to this condition in order to begin to understand how we can stop these mutations affecting the developing foetus. Because it is difficult to study embryonic development in humans we have generated a mouse model of this condition. In the mouse model just one gene (called Zic2) is altered and embryos that have two copies of this alteration develop the most severe form of cyclopia and die in the second half of gestation. This means that the normal role of this gene is to stop us developing HPE. We will use this mouse model to see just when and how the Zic2 gene prevents HPE. In addition, we will look to see what other genes Zic2 interacts with by breeding mice that carry the mutation in Zic2 with mice that carry a mutation in a second gene that can also cause HPE. These experiments are very important because if we understand how Zic2 and other genes protect us from HPE we can begin to design strategies to decrease the risk of a child developing this condition.Read moreRead less
Disorders Of Action Control And Learning-related Plasticity In The Basal Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$434,874.00
Summary
Disorders of the basal ganglia have long been known to produce severe cognitive symptoms including a deficit in the control of voluntary action. This project will assess the learning processes through which humans and other animals acquire such actions. We will systematically investigate changes in cellular plasticity associated with the acquisition of new actions to establish the role that it plays in action control under normal and pathological conditions.
Pathologies Of Action Control: Amygdala-striatal Interactions And The Development Of Habits.
Funder
National Health and Medical Research Council
Funding Amount
$431,867.00
Summary
Changes in basal ganglia function, whether produced by neurodegenerative disorders, stroke, injury or disease, can produce pathological changes in action control. This proposal will assess the role of amygdala afferents on basal ganglia structures, most notably the dorsal striatum, in this process. Using an animal model we will compare the role of central and basolateral amygdala inputs to striatum in decision-making, choice and the transition of actions to reflexive, habitual responses.