Generalized fear following acute stress is caused by change in co-transmitter identity of serotonergic neurons

Li, Huiquan; Jiang, Wen; Ling, L.; Gupta, V.; Chen, Cong; Pratelli, Marta; Godavarthi, Swetha K.; Spitzer, Nicholas C.

doi:10.1101/2023.05.10.540268

Cited by 4 publications

(3 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, there is evidence that the level of 5-HT-glutamate co-release may not be fixed but rather is plastic. For instance, changes in VGLUT3 expression in 5-HT neurons have been reported in rats exposed to chronic stress as well as during acquisition of generalized fear following acute stress . More generally, VGLUT3 expression is reported to vary during neurodevelopment and early postnatal life, , and point mutations of the gene encoding VGLUT3 (Slc17a8) may result in a life-long alteration in VGLUT3 expression .…”

Section: Resultsmentioning

confidence: 99%

“…For instance, changes in VGLUT3 expression in 5-HT neurons have been reported in rats exposed to chronic stress 52 as well as during acquisition of generalized fear following acute stress. 53 More generally, VGLUT3 expression is reported to vary during neurodevelopment and early postnatal life, 54,55 and point mutations of the gene encoding VGLUT3 (Slc17a8) may result in a life-long alteration in VGLUT3 expression. 56 If the latter changes in VGLUT3 expression occur in 5-HT neurons and affect the balance of 5-HT-glutamate at the synapse, the present data suggest that they could impact coping strategies and susceptibility to stress.…”

Section: Swim Stress Increased C-fos Expression In Drn Neuronsmentioning

confidence: 99%

See 1 more Smart Citation

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Gullino,

Fuller,

Dunn

et al. 2024

ACS Chem. Neurosci.

View full text Add to dashboard Cite

A major subpopulation of midbrain 5-hydroxytryptamine (5-HT) neurons expresses the vesicular glutamate transporter 3 (VGLUT3) and co-releases 5-HT and glutamate, but the function of this co-release is unclear. Given the strong links between 5-HT and uncontrollable stress, we used a combination of c-Fos immunohistochemistry and conditional gene knockout mice to test the hypothesis that glutamate co-releasing 5-HT neurons are activated by stress and involved in stress coping. Acute, uncontrollable swim stress increased c-Fos immunoreactivity in neurons co-expressing VGLUT3 and the 5-HT marker tryptophan hydroxylase 2 (TPH2) in the dorsal raphe nucleus (DRN). This effect was localized in the ventral DRN subregion and prevented by the antidepressant fluoxetine. In contrast, a more controllable stressor, acute social defeat, had no effect on c-Fos immunoreactivity in VGLUT3-TPH2 co-expressing neurons in the DRN. To test whether activation of glutamate co-releasing 5-HT neurons was causally linked to stress coping, mice with a specific deletion of VGLUT3 in 5-HT neurons were exposed to acute swim stress. Compared to wildtype controls, the mutant mice showed increased climbing behavior, a measure of active coping. Wildtype mice also showed increased climbing when administered fluoxetine, revealing an interesting parallel between the behavioral effects of genetic loss of VGLUT3 in 5-HT neurons and 5-HT reuptake inhibition. We conclude that 5-HT-glutamate co-releasing neurons are recruited by exposure to uncontrollable stress. Furthermore, natural variation in the balance of 5-HT and glutamate co-released at the 5-HT synapse may impact stress susceptibility.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Swim Stress Increased C-fos Expression In Drn Neuronsmentioning

confidence: 99%

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Gullino,

Fuller,

Dunn

et al. 2024

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In multiple brain regions, different addictive drugs cause alterations in the number of neurons expressing specific neurotransmitters ( Grieder et al, 2014 ; Kesby et al, 2017 ; Ladrón de Guevara-Miranda et al, 2017 ; James et al, 2019 ; Romoli et al, 2019 ), some of which have been linked to drug-induced changes in behavior ( James et al, 2019 ; Romoli et al, 2019 ; Pratelli et al, 2022 ). Activity-dependent changes in neurotransmitter phenotype linked to generalized fear and anhedonia have also been observed in the dorsal raphe in response to acute and chronic stress, respectively ( Li et al, 2023 ).…”

Section: Neurotransmitter Switching: Electrical Activity Regulates Ne...mentioning

confidence: 99%

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

González-González,

Conde,

Latorre

et al. 2024

Front. Integr. Neurosci.

Self Cite

View full text Add to dashboard Cite

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities.

show abstract

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD)

Ghaffarzadegan,

Akhondzadeh,

Nikasa

et al. 2024

Neurochem Res

View full text Add to dashboard Cite

Generalized fear following acute stress is caused by change in co-transmitter identity of serotonergic neurons

Cited by 4 publications

References 60 publications

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD)

Contact Info

Product

Resources

About