Trent Anderson

The brain is a fascinating lesson in duality - constantly balancing between the needs for diametrically opposed extremes. At its core it is an elegantly simplistic processing and computation center and yet its function results in the complicated behaviour, perception and reality we all experience. Built from simple single neurons the brain forms emergent networks that drive and govern our basic behaviour and how we perceive and interpret the world around us. Specifically, as a scientist I am intrigued by the duality of the balance the brain strikes between excitation and inhibition - tempering the need for excitatory activity to convey sensory and motor information with inhibitory activity that prevents run away excitation. Understanding the regulatory mechanisms that control this balance as well as the way disease states alter this balance has been the focus of my research career.

Did you know the brain consumes over 25% of the energy the body produces? This rate of consumption is 10 times greater than that of any other tissue. What is intriguing is given this extraordinary demand for energy the brain functions "inefficiently" - its excitatory activity is constantly being suppressed by an over-riding inhibitory activity. It is as if the brain is applying pressure to both the gas pedal and brake at the same time. The necessity for this inhibitory action is clearly evident as its loss or reduction has profound implication on the development and propagation of numerous disease states including epilepsy, Parkinson's disease, stroke and migraine. In the cerebral cortex, the higher order processing center of the brain, inhibitory interneurons are responsible for this "brake". These interneurons are a distinct and yet diverse group of specialized neurons with varying anatomical, pharmacologic and physiological properties that make them ideally situated to understand and manipulate this balance.

My research program combines aspects of cellular, synaptic and network neuroscience by using advanced tools in cellular physiology, neuropharmacology, imaging and molecular biology to elucidate mechanisms regulating excitability. Ongoing research points to neurosteroids as a prime candidate in regulating the balance between excitation and inhibition. Cortical neurons possess unique properties and sensitivities to neurosteroids that may be exploited to increase our understanding of the way the brain functions and as potential sources of therapeutic action. Steroids such as progesterone, pregnenonlone and dehydropiandrosterone are normally associated with their peripheral origin and action but have recently been shown to be de-novo synthesized in the brain itself. Specifically, several reports have indicated the ability of neurosteroids to alter both inhibitory (GABA) and excitatory (NMDA) function. Determining selective and novel pathways to up or down regulate the excitability of the brain may reveal significant sources of new therapeutic potential.