Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

Brockway, Dakota F.; Griffith, Keith R.; Aloimonos, Chloe M.; Clarity, Thomas T.; Moyer, J. Brody; Smith, Grace C.; Dao, Nigel C.; Hossain, Md Shakhawat; Drew, Patrick J.; Gordon, Joshua A.; Kupferschmidt, David A.; Crowley, Nicole A.

doi:10.1016/j.celrep.2023.112976

Cited by 9 publications

(3 citation statements)

References 61 publications

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“…A loss of SST interneuron inhibition in depression is implicated by reduced SST expression in human patients postmortem 16,17 , increased anxiety-and depression-like symptoms in rodents with brain-wide SST interneuron silencing 18 , and SST interneuron transcriptome deregulations compared to other cell types following chronic stress in rodents 19 . This is further supported by the joint inhibitory effects and co-release of SST and GABA 20,21 . SST interneurons mediate lateral inhibition through disynaptic loops 22,23 and maintain low Pyr neuron spike rates at baseline [24][25][26] .…”

Section: Introductionmentioning

confidence: 63%

Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity

Guet-McCreight,

Mazza,

Prevot

et al. 2024

Preprint

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Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, and new pharmacology boosting this inhibition via positive allosteric modulators of α5-GABAA receptors (α5-PAM) offers a promising effective treatment. However, testing the effect of α5-PAM on human brain activity is limited, meriting the use of detailed simulations. We utilized our previous detailed computational models of human depression microcircuits with reduced SST interneuron inhibition and α5-PAM effects, to simulate EEG of virtual subjects across depression severity and α5-PAM doses. We developed machine learning models that predicted optimal dose from EEG with high accuracy and recovered microcircuit activity and EEG. This study provides dose prediction models for α5-PAM administration based on EEG biomarkers of depression severity. Given limitations in doing the above in the living human brain, the results and tools we developed will facilitate translation of α5-PAM treatment to clinical use.

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Section: Introductionmentioning

confidence: 63%

Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity

Guet-McCreight,

Mazza,

Prevot

et al. 2024

Preprint

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“…Electrophysiology was conducted between 9-12 months of age (+/- 2 weeks; corresponding to about 6 months following the cessation of alcohol consumption) similar to our previously published work (Brockway et al, 2023; Sicher et al, 2023). Mice were exposed to an isoflurane chamber for deep anesthetization, the brain was quickly extracted and processed according to the N-methyl-D-glucamine (NMDG) protective recovery method (Ting et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

Smith,

Griffith,

Sicher

et al. 2024

Preprint

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Both alcohol use disorder (AUD) and Alzheimer's Disease and Related Dementias (ADRD) appear to include disruption in the balance of excitation and inhibition in the cortex, but their potential interactions are unclear. We examined the effect of moderate voluntary binge alcohol consumption on the aged, pre-disease neuronal environment by measuring intrinsic excitability and spontaneous neurotransmission on prefrontal cortical pyramidal (excitatory, glutamatergic) and non-pyramidal (inhibitory, GABAergic) neurons following a prolonged period of abstinence from alcohol in mice. Results highlight that binge alcohol consumption has lasting impacts on the electrophysiological properties of prefrontal cortical neurons. A profound increase in excitatory events onto layer 2/3 non-pyramidal neurons following alcohol consumption was seen, along with altered intrinsic excitability of pyramidal neurons, which could have a range of effects on Alzheimer's Disease progression in humans. These results indicate that moderate voluntary alcohol influences the pre-disease environment in aging and highlight the need for further mechanistic investigation into this risk factor.

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“…It has many functions, such as inhibiting the activity of the nervous system and the spontaneous electrical activity of the brain [17]. An injection of SS into the animal brain and spinal cord can effectively relieve pain [18]. In the clinic, SS can inhibit the production of antibodies via B lymphocytes and can also inhibit the release of inflammatory factors [19][20][21][22] to resist the inflammatory reaction.…”

Section: Introductionmentioning

confidence: 99%

Growth Axis Somatostatin, Growth Hormone Receptor, and Insulin-like Growth Factor-1 Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in Chinemys reevesii

Xie,

Liang,

Luo

et al. 2023

Genes

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In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the somatostatin (SS) gene, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-I) sequence of Chinemys reevesii. The effects of human growth hormone on the mRNA expression of growth-axis-related genes SS, GHR, and IGF-1 in different sexes were observed. The study of the SS gene in turtles using real-time fluorescence quantitative PCR showed that the SS gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the GHR gene and the IGF-I gene were expressed in all tissues of Chinemys reevesii. The SS gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the SS gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the GHR gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the GHR gene was reached at 3 and 4 weeks. In terms of the IGF-I gene, the changing trend of the expression level in the liver was the same as that of the GHR gene. After the injection of exogenous growth hormone, although the expression of the SS gene increased the inhibition of the secretion of the GHR gene by the Reeves’ turtle, exogenous growth hormone could replace the synthesis of GH and GHR, accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of SS, GHR, and IGF-1 genes, and promotes the growth of the Reeves’ turtle.

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Somatostatin peptide signaling dampens cortical circuits and promotes exploratory behavior

Cited by 9 publications

References 61 publications

Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity

Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity

Moderate Alcohol Consumption Induces Lasting Impacts on Prefrontal Cortical Signaling in Mice

Growth Axis Somatostatin, Growth Hormone Receptor, and Insulin-like Growth Factor-1 Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in Chinemys reevesii

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