Anatomical Substrates For Primate Executive Cortical Function
Funder
National Health and Medical Research Council
Funding Amount
$362,820.00
Summary
When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuit ....When studying the brain, many have been tempted to look for similarities in organization of cells and circuitry in different regions involved in various processes. While, at a first approximation, this may be a reasonable approach to understand how the brain works, it also ignores what makes the brain so complex: the diversity in its structure. In the late 19th, and early 20th, centuries, pioneering anatomists seized on the diversity in structure of the human brain. The study of cortical circuitry that underlies the diversity in cortical processing reached a zenith and there was a renaissance in understanding of brain function. These researchers were, however, limited by techniques available to them at the time. With the advent of new methodologies which allowed scientists to explore individual connections between cells (synapses), to probe structure and transmission across synapses, and to record from live neurones, new and exciting discoveries were made. However, these methodologies are highly time consuming and studies became necessarily more focussed. As a result, there was a tendency in the later half of the 20th century to extrapolate findings from one cortical area to cortex in general. Even more precarious, anatomical and functional findings in highly specialized sensory cortex of one species were projected to other distantly related species. Such thinking lead to a dark age in neuroscience. It became widely accepted that there exists a canonical circuit. Consequently, differences in function between different cortical areas were attributed solely to the source of their projections. The central thesis of this project is to study aspects of cell structure and cortical circuitry in the prefrontal lobe. We hope that the project will provide another step in the pathway that leads to understanding the mind.Read moreRead less
The Role Of Down Syndrome Candidate Region 1 (DSCR1) In Neurotransmitter Release, Vesicle Recycling And Down Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$352,318.00
Summary
Individuals with Down syndrome (DS) have three copies of human chromosome 21 (HSA21), rather than the normal two. The symptoms observed in DS individuals are therefore due to the overexpression of HSA21 genes. Since all individuals with DS develop symptoms in the brain similar to those see in Alzheimer's disease (AD), there may be a common mechanism that can be traced to the extra gene dosage from HSA21. We are interested in one of these genes, Down syndrome candidate region 1 (Dscr1), which is ....Individuals with Down syndrome (DS) have three copies of human chromosome 21 (HSA21), rather than the normal two. The symptoms observed in DS individuals are therefore due to the overexpression of HSA21 genes. Since all individuals with DS develop symptoms in the brain similar to those see in Alzheimer's disease (AD), there may be a common mechanism that can be traced to the extra gene dosage from HSA21. We are interested in one of these genes, Down syndrome candidate region 1 (Dscr1), which is overexpressed in both DS and AD brains. We hypothesise that Dscr1 has a role in regulating exocytosis, a process in which chemical messengers are released from cells. Exocytosis is highly specialised in the brain where neurotransmitters are released from neuronal synapses in a process known as synaptic transmission. Reduced synaptic transmission is one of the earliest hallmark of DS and AD occurring long before the classical neurological traits of DS and AD such as plaque formation and dementia. We propose that alterations in Dscr1 expression are responsible for the reduced neuronal exocytosis observed in the early stages of DS and AD. We have generated mice in which Dscr1 expression is altered, as occurs in DS and AD brains, and our preliminary studies indicate that exocytosis is reduced in these mice. We now wish to find the intracellular changes responsible for regulating exocytosis when Dscr1 expression is altered. We also aim to compare this to exocytosis in classical DS mouse models which have an extra chromosome 21 and in similar DS mouse models which have normal levels of Dscr1. This project will uncover the currently unknown functions of Dscr1 in exocytosis in an animal model, allow us to gauge whether Dscr1 is solely responsible for altering exocytosis in DS amongst other HSA21 genes, enable us to better understand the mechanisms initiating DS and AD and possibly lead to new targets of early intervention in these diseases.Read moreRead less
Mechanisms Underlying Short- And Long-term Plasticity At The Mossy Fibre -> CA3 Synapse In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$272,750.00
Summary
Synapses, the contacts between brain cells, are extremely plastic. They can become stronger and weaker depending on the activity they experience. The hippocampus, a structure in the brain, is known to be critical to the formation of conscious memories. The plastic nature of the synapse in this structure is thought to underlie learning and memory. Understanding the mechanisms that are responsible for the changes in synaptic strength in the hippocampus are therefore important to our understanding ....Synapses, the contacts between brain cells, are extremely plastic. They can become stronger and weaker depending on the activity they experience. The hippocampus, a structure in the brain, is known to be critical to the formation of conscious memories. The plastic nature of the synapse in this structure is thought to underlie learning and memory. Understanding the mechanisms that are responsible for the changes in synaptic strength in the hippocampus are therefore important to our understanding of learning and memory. This proposal describes a series of experiments that are designed to determine the mechanisms of plastic changes . We hope, that by understanding these mechanisms, we can start to understand how we learn and remember.Read moreRead less
Regulation Of Brain Development By Members Of The Fibroblast Growth Factor Family
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying ....The brain is the most complex organ in the body. It is made up of many different types of cells broadly classified into two classes called neurons and glia. The growth of the brain from a small population of immature neuroepithelial cells to many different types of neurons and glia is controlled by small potent proteins called growth factors. We understand that many different families of growth factors are involved in the development of the brain but not how they do what they do. We are studying the members of one particular family known as the Fibroblast Growth Factor family or FGFs. We want to find out how they instruct young brain cells to grow and divide and turn into mature neurons.Read moreRead less