Impact Of Somatic Versus Dendritic Inhibition On Neuronal Output
Funder
National Health and Medical Research Council
Funding Amount
$1,047,686.00
Summary
The brain is made up of literally billions of neurons connected in complex networks. These neurons come in two primary flavors - excitatory and inhibitory - which work in balance. Too much excitation and the brain becomes epileptic, too much inhibitory and we go into a coma. This proposal focuses on the role of specific inhibitory cell types in regulating brain function, and has relevant to a range of neurological disorders from epilepsy, to schizophrenia to depression.
The amygdala is a region of the brain involved in assinging emotional salience to our sensory world. Disorders of amygdala function lead to a range of anxiety related disorders. In this grant we aim to understand the neural circuits that are invovled in one form of learning that engages the amygdala - fear conditioning.
Understanding The Roles Of Dendritic Domains In Neuronal Function
Funder
National Health and Medical Research Council
Funding Amount
$491,509.00
Summary
We aim to find cellular basis to cognitive function and dysfunction by understanding the input/output characterstics of individual neurons. Since neurons are fundamental computational units in the brain, we aim to understand how synaptic inputs to different dendritic regions are processed prompting the neuron to fire an output. We also aim to seek distinct roles of certain dendritic branches in gating sensory inputs onto the neuron.
Regulation Of Cortical Excitability By GABAB Receptors
Funder
National Health and Medical Research Council
Funding Amount
$340,976.00
Summary
In the brain electrical activity either excites or inhibits nerve cells. Excitation is balanced by inhibition. If these two processes become unbalanced we can become unconscious or go into seizure. These extreme conditions emphasize the importance of the balance between excitation and inhibition in the brain. While there has been much work on the role of excitation, less is known about inhibition. In this project proposal we will investigate how inhibition regulates excitation in the cortex.
Elucidating The Mechanisms Of Alpha-conotoxin-induced Calcium Channel Inhibition Via G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$419,082.00
Summary
N-type voltage-gated calcium channels (VGCCs) are membrane proteins involved in neurotransmission and play a major role in pain. VGCCs are a well-established target for the development of analgesics. Our recent research identified that VGCCs can be inhibited by ?-conotoxins from the venom of marine snails by targeting ?-aminobutyric acid receptors in sensory neurons. We will characterize this novel form of modulation of VGCCs by ?-conotoxins and define the pathways that lead to VGCC inhibition.
Properties Of Dendritic Spines And Their Role In Synaptic Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Connections between nerve cells in the brain often occur onto enlarged protrusions called dendritic spines. This proposal will investigate the properties of dendritic spines, and relate differences in spine properties to synaptic plasticity. This information can be used to better understand and treat neurological disorders associated with spine malfunction, as occur in some forms of mental retardation, and may help with understanding the memory loss that occurs during ageing and dementia.
Do Changes In HCN Channels Function Cause Epilepsy?
Funder
National Health and Medical Research Council
Funding Amount
$386,172.00
Summary
About 100 000 people suffer from epilepsy in Australia with about one third poorly controlled with current anti-epileptic drugs. It is important to continue to develop novel modes of treatment for this debilitating disease. This project investigates an ion channel, known as HCN that is thought to be involved in making a brain epileptic. Understanding how changes in HCN channels make nerve cells and nerve networks more excitable will help us develop better strategies for designing drugs.
Neural Circuits For Odour-processing In The Rodent Piriform Cortex 'in Vivo'
Funder
National Health and Medical Research Council
Funding Amount
$488,817.00
Summary
We are studying the brain circuits that enable mammals to recognise odours. We will apply puffs of odorants to the nose of an anaesthetised mouse while measuring electrical signals in the odour-processing region of its cerebral cortex. Our work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the world. This is basic research that will, in the longer term, shed light on the disturbances that occur during mental illness.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.
Excitability And Hyperexcitability Of Neural Circuits In The Rodent Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$371,807.00
Summary
We are studying the properties of neurons (nerve cells) and brain circuits that enable mammals to recognise and remember odours. Our experiments will focus on neurons in the odour-processing region of the cerebral cortex of mice. This work will answer fundamental questions about how the brain interprets sensory inputs in order to build a coherent picture of the external world. Our findings will also provide a deeper understanding of the causes of epilepsy, leading to improved treatments.