Ventral Medial Prefrontal Cortex and Emotional Perseveration: The Memory for Prior Extinction Training

2. Ventral Medial Prefrontal Cortex and Emotional Perseveration: The Memory for Prior Extinction Training Maria A. Morgan, Jay Schulkin, Joseph E. LeDoux DepartmentofPsychology,NewYorkUniversity,NewYork,NY,USA CenterforNeuralScience,NewYorkUniversity,4WashingtonPI,Room809,NewYork,NY1003,USA ResearchDepartment,AmericanCollegeofObstetriciansandGynecologists,40912thSt.,SW,Washington,DC20024-2188,USA DepartmentofPhysiologyandBiophysics,GeorgetownUniversity,Washington,DC20024-2188,USA ClinicalNeuroendocrinologyBranch,NIMH,9000RockuillePike,Building10,Room2046,Bethesda,MD20892,USA Behavioural Brain Research 146 (2003) 121-130. Online [Available] elsevier.com/locate/bbr. Summarized by Shannon Juedes

3. How might mPFCv be involved in regulating extinction? • An inhibitory association develops in competition with the excitatory association developed during acquisition. • IL cortex is the crucial portion of mPFCv involved in extinction. • mPFCv is involved in utilizing the inhibitory association that develops during extinction. • Inhibitory is less stable and is dependent on the extinction context for expression. • mPFCvs may influence contextual conditioning and extinction by helping to integrate information about the internal environment wit the external environment.

4. How did this study come about? • Lesioned rats exhibited emotional perseveration. • Concluded that mPFCv plays a role in regulating fear inhibition during the extinction process. • Medial prefrontal cortex is involved in the extinction component of conditioned fear learning.

5. Prior Studies • Morrow et al. – mPFCv lesions disrupt extinction performance, whether lesions were made prior to or following acquisition training. • Quirk – The infralimbic cortex of the mPFCv is important for the retention of extinction.

6. Objectives • Two objectives • To examine the impact of post-acquisition lesions on the retention and extinction of fear responses • To examine the effectiveness of extinction by determining the extent to which reacquisition of fear responses is affected by prior extinction. • Lesioned animals would express more fear than controls during reacquisition, which would indicate that prior extinction trials were less effective in guiding their behavior.

7. Procedure • Male Sprague-Dawley rats • Housed in pairs upon arrival for 9 days • Unlimited assess to rat food and water • 12-h light:12-h dark cycles • 6 days later received 1 day context habituation and 2 days acquisition training • Rats in cages for 20-55 min • CS: sound • US: shock • Freezing response was the measure of conditioned emotional responding (fear acquisition). • Surgery day after • 2 groups—mPFCv (prelimbic/infralimbic cortical regions) and control

9. Procedure • 14-day recovery period • Extinction trials • 2 consecutive days of 5 s or fewer spent freezing • 2-3min later “reinstating US” • Ineffective in reinstating a CR to a CS for both control and lesioned animals • Extinction trials day after

10. Procedure • Reacquisition training next day • 4 groups • Control-delay (6) and mPFCv-delay (8) • Control-no-delay (7) and mPFC-no-delay (9) • Reextinction trials to criterion

12. Results

13. Results • When lesioned following acquisition training, mPFCv-lesioned animals responded less to the context than did controls. • L animals extinguished their response at the same rate as controls to the context. • L animals responded significantly more than control animals to both the context and CS upon reacquisition. • L animals showed resistance to extinction during reextinction relative to their own performance during the initial extinction session.

14. Implications • Changes in mPFCv may predispose one to develop fear responses that are difficult to extinguish or otherwise treat. • Functional activity in the mPFC and amygdala are inversely related.