Dynamic aspects of inhibitory synaptic transmission and modulation by neuroactive drugs

Funded Activity Summary

Information moving through the brain is typically encoded as brief bursts of signals. These signals travel along the microscopic wiring that connect the brain's nerve cells into complex circuits. Information is encoded in the frequency of the signals within a burst, and the duration of each burst. This frequency-coded information is processed at the contact points between nerve cells (synapses). Almost all neuroactive drugs target synapses, where they alter information processing. Most of the information about how neuroactive drugs work has been acquired from experiments performed under steady-state conditions. Typically, drugs are applied at a constant concentration and a synapse is stimulated at an unrealistically low frequency. The data obtained under these conditions are very useful, but tell only part of the story. For example, during an extended burst of signals, some neuroactive drugs may be displaced from their synaptic binding sites, reducing their effectiveness. In contrast, other drugs can only bind when synapses are active, and their effectiveness will increase during a burst of signals. For optimal drug design and delivery, it is important to understand how drugs work during bursts of activity. To date, the highly dynamic, non-equilibrium conditions encountered at central synapses have not been extensively studied. The central goal of this research proposal is to investigate the dynamic properties of synapses, and the drugs that modulate them. The results will provide insights into information processing in the brain, and will have significant implications for the development and targeting of clinically relevant neuropharmacological compounds.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $370,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical infection agents (incl. prions)

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

anaesthesia | brain cell cultures | brain function | dynamic process modelling | epiliepsy | hyperekplexia, Startle disease | ligand-gated ion channels | nerve terminals | pharmacokinetics | synaptic transmission

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