The Prefrontal Cortex

Communicates with the Amygdala

to Impair Learning after Acute
Stress in Females but not in Males

Lisa Y. Maeng, Jaylyn Waddell, Tracey J.

Shors

Presented by: Rima Shah

 Introduction

Traumatic life experiences tend to be

more debilitating to women than men
• 2x more likely to develop stress and anxiety-related
disorders
• Could this relate to gender differences in
stress response seen in animals?
 Stressors enhance eyeblink conditioning
in males and lead to profound learning deficits
in females
 Regions Implicated in Stress
Response
•In both males and
females:
Hippocampus and
Bed Nucleus Basolateral Nucleus
Stria terminalis (BLA) of amygdala
(BNST) involved in post-
stress learning
•Males: BNST
Medial Prefrontal
Cortex (mPFC)
interconnects these
regions
 mPFC and Stress

• Stress-related disorders associated with

differences in structure and function of mPFC
• Estrogen and mPFC in females:
 Ovariectomized female rats display
increased c-fos in mPFC after chronic
stress
 Experiments

1. Inactivate mPFC
2. Activate mPFC
3. Disrupt connection between mPFC and BLA
 Expts 1 and 2:
Subjects

• Male and cycling female Sprague Dawley

rats (90-120 days)
• Housed in groups of 3-4 before surgery
• Housed alone in standard, plastic,
“shoebox” after surgery
• Ad libitum access to food
• 12 hr light/dark cycle
 Expts 1 and 2:
Monitoring female estrus cycle

• Estrus cycle= Menstrual cycle in humans

• Phases- assessed via toluidine blue stain
• Rats lavaged daily to ensure normal cycle

Estrus

Rats Diestrus 1
were Proestrus
trained
Diestrus 2
Rats were stressed
 Expts 1 and 2:
Stress and Conditioning
Stress:
•7 days after sugery
•Infused with chemical prior to
stress
Stress= Loose restraint + 30
low intensity tail stimulations
Conditioning:
•CS- 80dB, 850ms burst white
noise
•US- 100ms, 0.5mA eyelid
stimulation
 Expts 1 and 2:
Surgery- mPFC cannulation
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.

**To ensure accuracy

of surgery:
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.Histological samples
taken after behavioral
tests
 Expts 1 and 2:
Infusions

Experiment 1: Experiment 2:
Inactivate mPFC Activate mPFC
0.5ug muscimol 0.5ul picrotoxin
(GABA-A receptor (GABA-A receptor
agonist) blocker)
CONTROL: aCSF CONTROL: saline
vehicle (artificial CSF) vehicle
 Males

Experiment
1:
Females
mPFC
inactivation
 Males

Experiment
2:
mPFC Females

activation
 Experiment 3:
Methods Summary
• Cycling female Sprague Dawley rats
• Monitored daily to ensure normal estrus cycle
• Stress procedure done 7 days after surgery
 Stressed during diestrus-2 phase of estrus cycle
• 24 hrs post stress (or none), conditioning training
began
 CS: white noise
 US: eyelid stimulation
Expt. 3: Surgery- mPFC-BLA
disconnection

QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
 Expt. 3: Histology of
mPFC-BLA disconnection
 Experiment 3:
mPFC-BLA disconnection
Females
Experiment 3:

Comparison
of
ipsilateral/
contralateral
connections
 Results Summary

• Experiments 1 and 2: mPFC is critically

involved in stress effect learning in females
but NOT in males
• Experiment 3: mPFC communicates with the
BLA to impair learning after stress in females
 mPFC implicated in stress and
learning
STRESS
• Densely populated with
glucocorticoid receptors
• Role in HPA stress response
• Stress exposure= dendritic
remodeling of mPFC
• Humans: stress-disorders
assocated with
structure/function of mPFC
LEARNING
Involved in associative
learning processes(ex.
eyeblink conditioning)
Modulates effects of
controllability on learning
processes
 Connections between mPFC and
amygdala

• Reciprocal connections:
 mPFC can suppress amygdalar activity
 mPFC inhibits amygdala during emotional learning
(extinction)

 Stimulation of amygdala modifies neuronal responses in mPFC

 Emotion impairs learning
 Fear conditioning inhibits prefrontal cortical neurons
Possible concurrent activity

Amygdala and mPFC may communicate

indirectly via the hippocampus

mPFC amygdala

hippocampus
 Individual Differences in stress
response
• Most studies about mPFC and BLA done in males
• Gender differences are prominent in many studies
• Is BLA-> mPFC connection completely absent in
males?
 Future studies may include disconnecting BLA-mPFC
connection in males
 Analyzing anatomical connections involved in stress and
learning using tractography and Diffusion tensor fMRI