Dissecting brain circuitry of fear and anxiety: The medial prefrontal cortex (mPFC)- Amygdala- periaqueductal grey (PAG) circuit

Master's Thesis


Anxiety, a debilitating sense of fear, involves an interconnected brain network that includes the medial prefrontal cortex (mPFC), amygdala, and periaqueductal grey (PAG). However, the specific organization and cellular physiology of distinct pathways within this network are undefined but critical for understanding anxiety disorders. This thesis elucidated the circuitry, pharmacology, and intrinsic physiology of defined pathways within the mPFC-amygdala-PAG circuit. Comparison of mPFC neurons projecting to the PAG versus amygdala revealed significant differences in intrinsic properties, local circuitry, and neuromodulation by stress peptides. In the central amygdala (CeA), neurons projecting to the PAG (CeA-PAG neurons) expressed different levels of hyperpolarization-activated current. CeA-PAG neurons were altered by anxiogenic peptide corticotropin-releasing factor (CRF) but not anxiolytic neuropeptide-Y (NPY). Optogenetic activation of axons originating in the PAG or IL drove both excitation and inhibition in CeA-PAG neurons. Together, this thesis has uncovered critical characteristics of a neural network implicated in anxiety.


Attribute NameValues
  • etd-04152015-100545

Author Ashley Nicole Ferreira
Advisor Patrick L. Sheets
Contributor Zainulabeuddin Syed, Committee Member
Contributor Sunny Boyd, Committee Member
Contributor Patrick L. Sheets, Committee Chair
Degree Level Master's Thesis
Degree Discipline Biological Sciences
Degree Name MS
Defense Date
  • 2015-04-03

Submission Date 2015-04-15
  • United States of America

  • medial prefrontal cortex

  • amygdala

  • electrophysiology

  • periaqueductal grey

  • University of Notre Dame

  • English

Record Visibility Public
Content License
  • All rights reserved

Departments and Units


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