Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area

Nagaeva, Elina; Zubarev, Ivan; Gonzales, Carolina Bengtsson; Forss, Mikko; Nikouei, Kasra; Miguel, Elena de; Elsilä, Lauri; Lindén, Anni‐Maija; Hjerling-Leffler, Jens; Augustine, George J; Korpi, Esa R.

doi:10.7554/elife.59328

Cited by 14 publications

(43 citation statements)

References 63 publications

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“…Given that GABAergic VTA cells are heterogeneous ( 13 , 27 , 28 ), and only a subset of VTA Vgat cells responded to SDS (Fig. 2B), we looked for subtypes of VTA GABA cells responsible for SDS-induced sleep.…”

Section: Vta Somatostatin Neurons Are Necessary For Sds-induced Sleepmentioning

confidence: 99%

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A specific circuit in the midbrain detects stress and induces restorative sleep

Zhao

Wang

et al. 2022

Science

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In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep could enable resilience, but how stress promotes sleep is unclear. Activity-dependent tagging revealed a subset of ventral tegmental area γ-aminobutyric acid (GABA)–somatostatin (VTA Vgat-Sst ) cells that sense stress and drive non–rapid eye movement (NREM) and REM sleep through the lateral hypothalamus and also inhibit corticotropin-releasing factor (CRF) release in the paraventricular hypothalamus. Transient stress enhances the activity of VTA Vgat-Sst cells for several hours, allowing them to exert their sleep effects persistently. Lesioning of VTA Vgat-Sst cells abolished SDS-induced sleep; without it, anxiety and corticosterone concentrations remained increased after stress. Thus, a specific circuit allows animals to restore mental and body functions by sleeping, potentially providing a refined route for treating anxiety disorders.

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Section: Vta Somatostatin Neurons Are Necessary For Sds-induced Sleepmentioning

confidence: 99%

“…S16, A and B). Because VTA Sst cells are heterogeneous ( 28 ), we examined the molecular identities of SDS-tagged cells (fig. S16C).…”

Section: Vta Somatostatin Neurons Are Necessary For Sds-induced Sleepmentioning

confidence: 99%

A specific circuit in the midbrain detects stress and induces restorative sleep

Zhao

Wang

et al. 2022

Science

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“…In addition to the presence of serotonergic cell bodies, dopaminergic cell bodies are also distributed in the VTA [ 165 ], an area of the brain that plays a role in reward-processed, and regulation of emotion and cognitive behaviours [ 166 ]. Although the neuropharmacological mechanisms of action of psilocybin are not definitively elucidated, there is evidence that, in addition to interaction with the serotonergic system, psilocybin also seems to interact, though not directly, with the mesolimbic dopaminergic pathway that plays a significant role in the brain’s reward system [ 165 ].…”

Section: Psilocybin Synthesismentioning

confidence: 99%

The Therapeutic Potential of Psilocybin

Toyang²,

et al. 2021

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The psychedelic effects of some plants and fungi have been known and deliberately exploited by humans for thousands of years. Fungi, particularly mushrooms, are the principal source of naturally occurring psychedelics. The mushroom extract, psilocybin has historically been used as a psychedelic agent for religious and spiritual ceremonies, as well as a therapeutic option for neuropsychiatric conditions. Psychedelic use was largely associated with the “hippie” counterculture movement, which, in turn, resulted in a growing, and still lingering, negative stigmatization for psychedelics. As a result, in 1970, the U.S. government rescheduled psychedelics as Schedule 1 drugs, ultimately ending scientific research on psychedelics. This prohibition on psychedelic drug research significantly delayed advances in medical knowledge on the therapeutic uses of agents such as psilocybin. A 2004 pilot study from the University of California, Los Angeles, exploring the potential of psilocybin treatment in patients with advanced-stage cancer managed to reignite interest and significantly renewed efforts in psilocybin research, heralding a new age in exploration for psychedelic therapy. Since then, significant advances have been made in characterizing the chemical properties of psilocybin as well as its therapeutic uses. This review will explore the potential of psilocybin in the treatment of neuropsychiatry-related conditions, examining recent advances as well as current research. This is not a systematic review.

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“…3c, 4b). We previously demonstrated that different electrophysiological subtypes of the VTA Sst neurons have distinct locations, assigning anterolateral VTA neurons to either afterdepolarizing (ADP) or high-frequency firing (HFF) subtypes (Nagaeva et al, 2020). Therefore, we took an effort to define the electrophysiological subtype of the projecting neurons.…”

Section: The Majority Of Vta Sst Projecting Neurons Have Electrophysi...mentioning

confidence: 99%

Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response

Nagaeva

Schäfer

Lindén

et al. 2023

Preprint

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Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Recently, we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighbouring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that VTA Sst neurons also project far outside the VTA and innervate several forebrain regions that are mainly involved in the regulation of emotional behaviour. When we deleted these VTA Sst neurons several behaviours and drug effects were affected, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to inescapable stress of forced swimming, often in a sex-dependent manner. Interestingly, the majority of these Sst projecting neurons was found to express Vglut2 and Th, but not Dat. Together, these data demonstrate that VTA Sst neurons have their selective projection targets, which are distinct from the main targets of VTA dopamine neurons and involved in the regulation of a variety of behaviours mostly associated with the stress response. This, in turn, makes these VTA neurons a meaningful addition to the somatostatinergic system of the brain.

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Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area

Cited by 14 publications

References 63 publications

A specific circuit in the midbrain detects stress and induces restorative sleep

A specific circuit in the midbrain detects stress and induces restorative sleep

The Therapeutic Potential of Psilocybin

Somatostatin-expressing neurons in the ventral tegmental area innervate specific forebrain regions and are involved in the stress response

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