Aarhus University Seal / Aarhus Universitets segl

Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats. / Czeh, Boldizsar; Vardya, Irina; Varga, Zsofia; Febbraro, Fabia; Csabai, David; Martis, Lena-Sophie; Højgaard, Kristoffer; Henningsen, Kim; Bouzinova, Elena; Miseta, Attila; Jensen, Kimmo; Wiborg, Ove.

In: Frontiers in Cellular Neuroscience, Vol. 12, 148, 20.06.2018.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Czeh, Boldizsar ; Vardya, Irina ; Varga, Zsofia ; Febbraro, Fabia ; Csabai, David ; Martis, Lena-Sophie ; Højgaard, Kristoffer ; Henningsen, Kim ; Bouzinova, Elena ; Miseta, Attila ; Jensen, Kimmo ; Wiborg, Ove. / Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats. In: Frontiers in Cellular Neuroscience. 2018 ; Vol. 12.

Bibtex

@article{e7f121d3738e467d9ab8ad85f0072b2f,
title = "Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats",
abstract = "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.",
keywords = "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",
author = "Boldizsar Czeh and Irina Vardya and Zsofia Varga and Fabia Febbraro and David Csabai and Lena-Sophie Martis and Kristoffer H{\o}jgaard and Kim Henningsen and Elena Bouzinova and Attila Miseta and Kimmo Jensen and Ove Wiborg",
year = "2018",
month = jun,
day = "20",
doi = "10.3389/fncel.2018.00148",
language = "English",
volume = "12",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media S.A",

}

RIS

TY - JOUR

T1 - Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats

AU - Czeh, Boldizsar

AU - Vardya, Irina

AU - Varga, Zsofia

AU - Febbraro, Fabia

AU - Csabai, David

AU - Martis, Lena-Sophie

AU - Højgaard, Kristoffer

AU - Henningsen, Kim

AU - Bouzinova, Elena

AU - Miseta, Attila

AU - Jensen, Kimmo

AU - Wiborg, Ove

PY - 2018/6/20

Y1 - 2018/6/20

N2 - 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.

AB - 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.

KW - depressive disorder

KW - infralimbic cortex

KW - interneuron

KW - learning

KW - NPY

KW - patch-clamp

KW - resilience

KW - chronic stress

KW - CHRONIC MILD STRESS

KW - MAJOR DEPRESSIVE DISORDER

KW - AMINOBUTYRIC-ACID LEVELS

KW - MAGNETIC-RESONANCE SPECTROSCOPY

KW - GABA(B) RECEPTORS

KW - NEUROPEPTIDE-Y

KW - DENTATE GYRUS

KW - ACTIVE ZONE

KW - NEUROTRANSMITTER RELEASE

KW - PERISOMATIC INHIBITION

U2 - 10.3389/fncel.2018.00148

DO - 10.3389/fncel.2018.00148

M3 - Journal article

C2 - 29973870

VL - 12

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

M1 - 148

ER -