Effects of Electrical Stimulation of the Rodent Infralimbic Cortex on Hippocampal Neurogenesis
¹Ashwin G Ramayya, ^1,2John Rolston, ¹Claire-Anne Gutekunst, and ¹Robert E. Gross
¹Dept. of Neurosurgery, Emory University, Atlanta, GA
²Dept. of Biomedical Engineering, Georgia Tech, Atlanta, GA

Introduction

In the mammalian brain, the production of neurons from neuronal stem/progenitor cells is an active process that occurs exclusively in two main sites: the subventricular zone and the hippocampal subgranular zone. Many physiological and pathological conditions, including major depression, have been shown to affect neurogenesis in the hippocampus (Toda et al. 2008). Specifically, major depression has been shown to decrease the rate of hippocampal neurogenesis, while almost all known anti-depressant therapies (from various classes of drugs to electroconvulsive therapy and physical activity) have been shown to increase the rate of hippocampal neurogenesis (Kempermann and Kronenberg 2003).

In humans, DBS of the anterior subgenual cingulate (BA 25) is a novel surgical therapy that has been shown to have beneficial anti-depressant effects (Mayberg et al. 2005). However, the mechanism by which this technique exerts its anti-depressant effects is still largely unknown. We aim to use an adult rodent model to investigate the effects that DBS of the infralimbic cortex (IL; rodent homologue of BA 25) has on hippocampal neurogenesis, and gain insight on the general mechanism by which this novel surgical technique exerts its therapeutic effects.

Fig. 1: The Hippocampus



Fig 2: Deep Brain Stimulation for Major Depression



Fig 3:Infralimbic Cortex: Rodent Homologue of BA 25

Methods and Materials

Results

Fig 4: Increased Zif/268 (Red) Expression in Dentate Gyrus of the Stimulated Brain (n=3)

Conclusions and Future Studies

The increased Zif/268 expression in the dentate gyrus of S1 and S2 indicates that electrical stimulation of the IL upregulates cellular activity in the hippocampus.

The increased cellular activity most likely includes both neuronal and glial activity. The S2 cells exclusively expressing Zif/268 are most likely glial cells, while the cells co-localizing Zif/268 and NeuN are mature neurons.

After studying the effects of high-frequency IL stimulation on hippocampal neurogenesis, we hope to study the effects of IL lesions on hippocampal neurogenesis. This will shed light on a) the physiological effect that high-frequency electrical stimulation has on the IL, b) the way in which the IL regulates neurogenesis.

Resources

Acknowledgements: We would like to thank Dr. Collin Franz and Dr, Enrique Torre for offering much needed technical advice. Funding was offered by Emory University’s Research Committee

References

-Kempermann G, Kronenberg G. 2003. Depressed New Neurons?--Adult Hippocampal Neurogenesis and a Cellular Plasticity Hypothesis of Major Depression. Neuroscience Perspectives. 54:499-503.
-Mayberg H, Lozano A, Voon V, McNeely H, Seminowicz D, Hamani C, Schwalb J, Kennedy S. 2005. Deep Brain Stimulation for Treatment-Resistant Depression. Neuron. 45:651-660.
-Paxinos G, Watson C. 1986. The Rat Brain in Stereotactic Coordinates. New York: Academic Press.
-Shumake J, Poremba A, Edwards E, Gonzalez-Lima F. 2000. Congenital helpless rats as a genetic model for cortex metabolism in depression. NeuroReport. 11:3793-3798.
-Toda H, Hamani C, Fawcett A, Hutchison W, Lozano A. 2008. The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation. Journal of Neurosurgery.132-138.