Effects of High Frequency Electrical Stimulation of the InfralimbicCortex on Cellular Activity in the Rodent Brain Open Access

Abstract

Deep brain stimulation (DBS) of the subgenual cingulate (Cg25) white matter (WM) is a novel surgical therapy which has recently been used to treat severely depressed, treatment-resistant individuals. While it has shown significant therapeutic effects, the mechanism by which DBS achieves clinical benefits is not completely understood. Functional neuroimaging studies have shown that Cg25WM DBS leads to a suppression of metabolic activity in the Cg25, which is a known mediator of negative mood. In this study, we aimed to gain some understanding of how this occurs by studying the effects of acute high frequency stimulation (HFS) on cellular activity in the rodent brain. We targeted the infralimbic cortex (IL), the rodent homologue of Cg25, and quantified cellular activity by measuring the density of cells expressing c-fos, an Immediate Early Gene (IEG) which is expressed in the nucleus of active cells. We compared cellular activity in stimulated and non-stimulated rats locally in the IL, in the monosynaptically connected basomedial amygdala (BMA) and the polysynaptically connected hippocampal dentate gyrus (DG). We found there to be a greater cellular activity in all three regions of the stimulated brain, suggesting that Cg25WM DBS has far-reaching acute effects on cellular activity. The increased cellular activity in the IL was found to be statistically significant; however, there were not enough subjects to conclusively determine the significance of increased cellular activity in the BMA and the DG.

Table of Contents

I.Introduction..........................................................................................1-7

II.Materials and Methods

a. Experimental Animals............................................................................ 7

b. Surgery .............................................................................................7-8

c. Experimental Design .............................................................................8

d. Tissue Collection and Immunohistochemistry .............................................8

e. Image Quantification ............................................................................8-9

f. Statistical Analysis ...............................................................................9

III.

Results

a. Electrode Location ...............................................................................9-10

b. Cfos Antibody Binding ..........................................................................10

c. ShamElectrode Subjects.......................................................................10

d. IL Cfos Activity...................................................................................10-11

e. Basomedial Amygdala (BMA) Cfos Activity.................................................11-12

f. Hippocampal Dentate Gyrus (DG) Cfos Activity..........................................12

IV. Discussion

a. Summary...........................................................................................12-14

b. ShamElectrode Findings........................................................................14-15

c. Increased Cellular Expression in BMA after HFS..........................................15-16

d. Increased Cellular Expression in DG after HFS............................................16-18

V. Limitations.............................................................................................18-19

VI. Conclusion.............................................................................................19-20

VI. Future Directions.....................................................................................20

VI. References.............................................................................................21-29

IX. Tables and Figures

a. Table 1...............................................................................................30

b. Figure 1..............................................................................................31

c. Figure 2..............................................................................................32

d. Figure 3..............................................................................................33

e. Figure 4..............................................................................................34

f. Figure 5...............................................................................................35

g. Figure 6..............................................................................................36

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Keyword	depression c-fos infralimbic cortex subgenual cingulate electrical stimulation deep brain stimulation
Committee Chair / Thesis Advisor	Gross, Robert, Emory University
Committee Members	Konner, Melvin J, Emory University Mayberg, Helen S, Emory University Rilling, James K, Emory University

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