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Long-Term Stress Di...
Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats
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Czeh, B. (author)
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Vardya, I. (author)
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Varga, Z. (author)
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Febbraro, F. (author)
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Csabai, D. (author)
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Martis, L. S. (author)
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Hoigaard, K. (author)
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Henningsen, K. (author)
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Bouzinova, E. V. (author)
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Miseta, A. (author)
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- Jensen, Kimmo (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Wiborg, O. (author)
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(creator_code:org_t)
- 2018-06-20
- 2018
- English.
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In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
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Abstract
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- Clinical and experimental data suggest that fronto-cortical GABAergic deficits contribute to the pathophysiology of major depressive disorder (MDD). To further test this hypothesis, we used a well characterized rat model for depression and examined the effect of stress on GABAergic neuron numbers and GABA-mediated synaptic transmission in the medial prefrontal cortex (mPFC) of rats. Adult male Wistar rats were subjected to 9-weeks of chronic mild stress (CMS) and based on their hedonic-anhedonic behavior they were behaviorally phenotyped as being stress-susceptible (anhedonic) or stress-resilient. Post mortem quantitative histopathology was used to examine the effect of stress on parvalbumin (PV)-, calretinin- (CR), calbindin- (CB), cholecystokinin- (CCK), somatostatin-(SST) and neuropeptide Y-positive (NPY+) GABAergic neuron numbers in all cortical subareas of the mPFC (anterior cingulate (Cg1), prelimbic (PrL) and infralimbic (IL) cortexes). In vitro, whole-cell patch-clamp recordings from layer II-III pyramidal neurons of the ventral mPFC was used to examine GABAergic neurotransmission. The cognitive performance of the animals was assessed in a hippocampal-prefrontal-cortical circuit dependent learning task. Stress exposure reduced the number of CCK-, CR- and PV-positive GABAergic neurons in the mPFC, most prominently in the IL cortex. Interestingly, in the stress-resilient animals, we found higher number of neuropeptide Y-positive neurons in the entire mPFC. The electrophysiological analysis revealed reduced frequencies of spontaneous and miniature IPSCs in the anhedonic rats and decreased release probability of perisomatic-targeting GABAergic synapses and alterations in GABA(B) receptor mediated signaling. In turn, pyramidal neurons showed higher excitability. Anhedonic rats were also significantly impaired in the object-place paired-associate learning task. These data demonstrate that long-term stress results in functional and structural deficits of prefrontal GABAergic networks. Our findings support the concept that fronto-limbic GABAergic dysfunctions may contribute to emotional and cognitive symptoms of MDD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- depressive disorder
- infralimbic cortex
- interneuron
- learning
- NPY
- patch-clamp
- resilience
- chronic stress
- chronic mild stress
- major depressive disorder
- aminobutyric-acid
- levels
- magnetic-resonance spectroscopy
- gaba(b) receptors
- neuropeptide-y
- dentate gyrus
- active zone
- neurotransmitter release
- perisomatic inhibition
- Neurosciences & Neurology
- erio dc
- 1984
- journal of microscopy
- v134
- p127
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Czeh, B.
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Vardya, I.
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Varga, Z.
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Febbraro, F.
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Csabai, D.
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Martis, L. S.
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show more...
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Hoigaard, K.
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Henningsen, K.
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Bouzinova, E. V.
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Miseta, A.
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Jensen, Kimmo
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Wiborg, O.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
- Articles in the publication
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Frontiers in Cel ...
- By the university
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University of Gothenburg