[Frontiers in Bioscience 9, 40-47, January 1, 2004]

TRACING FUNCTIONAL CIRCUITS USING C-FOS REGULATED EXPRESSION OF MARKER GENES TARGETED TO NEURONAL PROJECTIONS

Mark Murphy, Ursula Greferath, Nupur Nag, Jess Nithianantharajah and Yvette M Wilson

Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria 3010, Australia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. FTL mouse
4. Circuits involved in body fluid homeostasis
5. Analysis of circuits activated by light in the retina in FTL mice
6. Studies on learning and memory
7. Fear conditioning studies with the FTL mice
8. Environmental enrichment
9. Detection of synaptic change
10. Perspective
11. Acknowledgements
12. References

1. ABSTRACT

We have developed novel techniques to trace functionally activated circuits and synaptic plasticity within the brain. We have generated transgenic mice, FTL, which contain a tau-lacZ fusion gene regulated by the promoter for c-fos. Following a particular nervous system stimulation in these mice, only neurons, which are functionally activated, will express LacZ, which is targeted to neuronal processes by the tau protein. In the FTL mice, we found highly inducible expression of lacZ by a range of different stimuli, and successful targeting of expression to neuronal cell bodies, axons and dendrites. To test if a functionally activated circuit could be visualized, the mice were deprived of water, which activates nuclei involved in body fluid homeostasis. LacZ was induced in these nuclei and their projections, allowing the mapping of a neuroendocrine circuit. Further studies have employed these mice in the analysis of neurons and circuits activated in vision, and learning and memory. We have also developed methods to measure markers of synaptic plasticity in the brain, and found significant experience dependent changes in the levels of these markers in different parts of the brain. We believe these techniques will aid in the identification of circuits for many different brain functions, and within those circuits, the locations of synaptic plasticity.