EXPLORING THE ‘LEARNED HELPLESSNESS’ PATHWAY

MAIER/WATKINS LABBURST PRESENTATIONTYLER FAIRAUGUST 5TH, 2014

PREVIEW

• Importance• Learned Helplessness• Related Brain Regions• Method• Future Direction• Acknowledgements • Questions?

IMPORTANCE

• Why is this research important?• Personal connection• My goals

LEARNED HELPLESSNESS

• 1960’s University of Pennsylvania researcher Martin Seligman discovered ‘Learned Helplessness.’• Inability for dog to escape shock in a harness impacts their

behavior in a shuttlebox.• Dogs that control stress had different reaction.

• Yoked pair system• Long-term behavioral changes

RELATED BRAIN REGIONS

• One of the researchers in Seligman’s lab was Steven Maier.• Dorsal Raphe Nucleus (DRN)• Too small to be responsible

• Ventral Medial Prefrontal Cortex (mPFC)• Control inhibited brain activity, rather than lack of control.

mPFC

DRN

• Lateral Habenula (LH)• Excitatory neural messages to DRN• Associated with anxiety and fear

LH

RAT BRAIN

METHOD: PART ONE

• Goal: Better understanding the LHb-to-DRN pathway.1. Surgical injection of a tracer into the DRN2. Stressing animals in yoked pairs3. Sacrifice animals and tissue collection4. Staining technique, immunohistochemistry (c-fos)5. Microscopic quantification

METHOD: PART TWO

• Goal: What happens to rat behavior when LHb-to-DRN circuit is turned off?• Optogenetics.1. Surgical injection of virus carrying cellular

channel halorhodopsin.2. Run juvenile social exploration (JSE) baseline.3. Run stress.4. Run JSE again to measure resulting change in behavior.

FUTURE DIRECTION

• Continue with preliminary steps taken over the summer• If the proposed pathway results in behavioral change, explore

treatment.• Ketamine injection

• Benefits for humans

ACKNOWLEDGMENTS

• Thanks to the following:• Sam Dolzani• BURST• Maier/Watkins Lab

QUESTIONS?