Somatostatin interneurons in the prefrontal cortex control affective state discrimination in mice

Scheggia, Diego; Managò, Francesca; Maltese, Federica; Bruni, Stefania; Nigro, Marco; Dautan, Daniel; Latuske, Patrick; Contarini, Gabriella; Gómez-Gonzalo, Marta; Requie, Linda Maria; Ferretti, Valentina; Castellani, Giulia; Mauro, Daniele; Bonavia, Alessandra; Carmignoto, Giorgio; Yizhar, Ofer; Papaleo, Francesco

doi:10.1038/s41593-019-0551-8

Cited by 128 publications

(122 citation statements)

References 57 publications

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“…As to be expected, the SOM cells within the PFC are involved in many functions; for example, some PFC SOM cells contribute to reading emotions (affective state discrimination) 52 , others encode fear memories 53 ; and locally opto-activating neocortical NOS1 and SOM cells increases cerebral blood flow 54,55 . The c-fosdependent activity-tagging technique allows the SOM/GABA cells that become activated by sleep deprivation to be highlighted from the other functions that these cells carry out.…”

mentioning

confidence: 79%

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Tossell

Soto

et al. 2020

Preprint

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AbstractAnimals undertake specific behaviors before sleep. Little is known about whether these innate behaviors, such as nest building, are actually an intrinsic part of the sleep-inducing circuitry. We found, using activity-tagging genetics, that mouse prefrontal cortex (PFC) somatostatin/GABAergic (SOM/GABA) neurons, which become activated during sleep deprivation, induce nest building when opto-activated. These tagged neurons induce sustained global NREM sleep if their activation is prolonged metabotropically. Sleep-deprivation-tagged PFC SOM/GABA neurons have long-range projections to the lateral preoptic (LPO) and lateral hypothalamus (LH). Local activation of tagged PFC SOM/GABA terminals in LPO and the LH induced nesting and NREM sleep respectively. Our findings provide a circuit link for how the PFC responds to sleep deprivation by coordinating sleep preparatory behavior and subsequent sleep.

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confidence: 79%

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Tossell

Soto

et al. 2020

Preprint

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“…In PrL, parvalbumin (PV) and somatostatin (SOM) interneurons are the two largest genetically defined and also the most‐studied GABA interneurons in psychiatric problems 18,21,32‐36 . PV interneuron is a kind of fast‐spiking interneurons that located surround pyramidal neurons, 15 and play important role in the information integration and neuroplasticity in cortical circuits of PrL 16,33,37,38 .…”

Section: Discussionmentioning

confidence: 99%

Electro‐acupuncture alleviates adolescent cocaine exposure‐enhanced anxiety‐like behaviors in adult mice by attenuating the activities of PV interneurons in PrL

Nie

Wei

et al. 2020

FASEB j.

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We recently found that adolescent cocaine exposure (ACE) resulted in an enhancement of the γ‐aminobutyric acid (GABA) neurotransmitter system in the prelimbic cortex (PrL) of adult mice. Here, we aim to further investigate the role of GABAergic transmission, especially parvalbumin (PV) interneurons within PrL in the development of ACE‐induced anxiety‐like behavior, and to assess whether and how electro‐acupuncture (EA) therapeutically manage the ACE‐induced abnormal behaviors in adulthood. ACE mice exhibited the enhanced anxiety‐like behaviors in their adulthood, accompanied by increased GABAergic transmission and PV interneurons in PrL. Chemogenetic blocking PV interneurons in PrL alleviated ACE‐enhanced anxiety‐like behaviors in mice. Importantly, 37‐day EA treatments (mixture of 2 Hz/100 Hz, 1 mA, 30 minutes once a day) at the acupoints of Yintang (GV29) and Baihui (GV20) also alleviated ACE‐induced anxiety‐like behaviors, and rescued ACE‐impaired GABAergic neurotransmitter system and PV interneurons in PrL. In parallel, EA treatments further suppressed the activities of pyramidal neurons in PrL, suggesting that EA treatments seem to perform it beneficial effects on the ACE‐induced abnormal emotional behaviors by “calming down” the whole PrL. Collectively, these findings revealed that hyper‐function of GABAergic transmission, especially mediating by PV interneurons in PrL may be key etiology underlying ACE‐induced anxiety‐like behaviors. At least by normalizing the function of GABAergic and PV interneurons, EA may represent a promising therapeutic strategy for managing adolescent substance use‐related emotional disorders.

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“…In depression, SST related expression is consistently downregulated within the sgACC and amygdala of patients 28,61 . Modulation of SST interneuron activity experimentally reduces depressive-like behavior in animal models of depression 42 , and is selectively tied to affective state discrimination in rodents 43 . Given evidence that SST expression is sensitive to BDNF and is cAMP dependent, depression related decreases in SST may reflect differences in neuronal activity rather than altered cell morphology or number 62,63 .…”

Section: Discussionmentioning

confidence: 99%

“…Reductions in somatostatin (SST) gene expression are a pronounced pathophysiological feature of depression 11,38 , underscored by the preferential expression of SST markers in cortico-striatal reward circuitry and mPFC in donor tissue from healthy populations 36,39 . SST expression is reduced within dorsolateral prefrontal cortex and subgenual mPFC in patients with depression 40,41 , and experimental manipulation of SST neurotransmission in rodents modulates anxiolytic and antidepressant behaviors 42 as well as socioaffective processing 43 . Depression linked alterations in the function of GABAergic cells, including SST, may influence signal-tonoise properties of cortex and global measures of connectivity 11,38 , which could be reflected depression-related differences in RSFA and GBC.…”

Section: In-vivo Depression Imaging Phenotypes Track Ex-vivo Expressimentioning

confidence: 99%

Convergent molecular, cellular, and neural signatures of major depressive disorder

Anderson

Collins

Kong

et al. 2020

Preprint

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Figures Count: Main text (6), Supplementary (9) Word count: Abstract (244), Introduction (821), Results (2,553), Discussion (1,689) References: Main text (77), Methods only (29) Supplementary Data Tables: 15 Code repository: 1 Key Findings 1. Major depressive disorder and negative affect are associated with replicable profiles of cortical anatomy and function across independent population-level neuroimaging datasets (combined N≥23,723). 2. Somatostatin interneurons are consistent spatial transcriptional associates of in-vivo depression-linked imaging phenotypes. 3. Integrative single-cell gene expression analysis associate somatostatin interneurons and astrocytes with both in-vivo depression-linked imaging and ex-vivo gene downregulation in independent MDD cortical tissue samples. 4. Transcriptional correlates of in-vivo depression imaging phenotypes selectively capture gene downregulation in post-mortem tissue samples from patients with depression, but not other psychiatric disorders.5. Indicating that some cell classes are preferentially sensitive to inherited disease liability, genome-wide risk for depression is enriched among interneurons, but not glia.6. Gene associates of depression-linked anatomy and function identify specific neurotransmitter systems, molecular signaling pathways, and receptors, suggesting possible targets for pharmaceutical intervention. AbstractMajor depressive disorder emerges from the complex interactions of biological systems that span across genes and molecules through cells, circuits, networks, and behavior.Establishing how neurobiological processes coalesce to contribute to the onset and maintenance of depression requires a multi-scale approach, encompassing measures of brain structure and function as well as genetic and cell-specific genomic data. Here, we examined anatomical (cortical thickness) and functional (functional variability, global brain connectivity) correlates of depression and negative affect across three population-imaging datasets: UK Biobank, Genome Superstruct Project, and ENIGMA (combined N≥23,723). Integrative analyses incorporated measures of cortical gene expression, post-mortem patient transcriptional data, depression GWAS, and single-cell transcription. Neuroimaging correlates of depression and negative affect were consistent across the three independent datasets. Linking ex-vivo gene downregulation with in-vivo neuroimaging, we found that genomic correlates of depression-linked neuroimaging phenotypes tracked gene downregulation in post-mortem cortical tissue samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data implicated somatostatin interneurons and astrocytes as consistent cell associates of depression, through both in-vivo imaging and ex-vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multi-scale appro...

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Somatostatin interneurons in the prefrontal cortex control affective state discrimination in mice

Cited by 128 publications

References 57 publications

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Sleep deprivation triggers somatostatin neurons in prefrontal cortex to initiate nesting and sleep via the preoptic and lateral hypothalamus

Electro‐acupuncture alleviates adolescent cocaine exposure‐enhanced anxiety‐like behaviors in adult mice by attenuating the activities of PV interneurons in PrL

Convergent molecular, cellular, and neural signatures of major depressive disorder

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