Chronic unpredictable stress promotes cell-specific plasticity in prefrontal cortex D1 and D2 pyramidal neurons
E M Anderson1, D Gomez1, A Caccamise1
1Department of Biomedical Sciences, Marquette University, Milwaukee, WI, 53233, USA.
Neurobiology of Stress
|April 3, 2019
Summary
Chronic unpredictable stress (CUS) induces affective behaviors and alters neuronal function in mice. Specific dopamine receptor-expressing neurons in the medial prefrontal cortex show distinct stress-induced changes, impacting neural circuits.
Area of Science:
- Neuroscience
- Psychiatry
- Cellular Biology
Background:
- Unpredictable stress is a significant risk factor for neuropsychiatric disorders like depression, anxiety, and PTSD.
- The medial prefrontal cortex (mPFC) is a key brain region affected by stress, contributing to psychiatric phenotypes.
- Identifying common circuit-level mechanisms underlying stress-related disorders is crucial for understanding pathophysiology.
Purpose of the Study:
- To establish a chronic unpredictable stress (CUS) model in mice that reliably induces affective behaviors.
- To investigate stress-induced alterations in the intrinsic excitability and synaptic regulation of mPFC layer 5/6 pyramidal neurons.
- To differentiate the effects of CUS on distinct neuronal subpopulations expressing dopamine D1 and D2 receptors.
Main Methods:
- Adult male C57BL6J mice were subjected to 'less intense' or 'more intense' CUS protocols.
- Behavioral assessments included sucrose preference (anhedonia), elevated plus maze (anxiety), and forced swim test (depression-like behaviors).
- Whole-cell patch-clamp recordings were performed on prelimbic (PrL) and infralimbic (IL) mPFC layer 5/6 pyramidal neurons post-stress.
Main Results:
- More intense CUS induced significant anhedonia, anxiety, and depressive-like behaviors; less intense CUS did not.
- Dopamine D1-receptor-expressing pyramidal neurons (D1-PYR) in the PrL showed increased excitability but impaired firing at high potentials.
- Dopamine D2-receptor-expressing pyramidal neurons (D2-PYR) exhibited reduced excitability and firing frequency; both subpopulations showed altered synaptic currents.
Conclusions:
- More intense CUS effectively models affective behaviors and induces specific neuroplastic changes in mPFC subpopulations.
- D1-PYR and D2-PYR exhibit differential intrinsic and synaptic plasticity in response to CUS, suggesting distinct roles in stress pathology.
- These stress-induced adaptations in neuronal subpopulations may underlie the pathophysiology of stress-related neuropsychiatric disorders.
Keywords:
Affective behaviorDopamine receptorExcitatory and inhibitory synaptic transmissionIntrinsic excitabilityPrefrontal cortexStressMore Related Videos
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