Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

Pohodich, Amy E.; Yalamanchili, Hari Krishna; Raman, Ayush T.; Wan, Ying-Wooi; Gundry, Michael C.; Hao, Shuang; Jin, Haijing; Tang, Jianrong; Liu, Zhandong; Zoghbi, Huda Y.

doi:10.7554/elife.34031

Cited by 48 publications

(37 citation statements)

References 89 publications

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“…This new DBS apparatus allows unrestricted moving and feeding of experimental animals and delivers long-term chronic stimulation (at the effective voltage for over 3 months), which is more advantageous than the majority of previous DBS devices used for rodent models ( 32 , 33 ). We have observed that HF-DBS increases the expression of activity-dependent genes c-fos and Npas4 in the AI, which suggests our stimulation protocol modulates AI cellular activity and is in line with previous DBS studies ( 34 – 37 ).…”

Section: Discussionsupporting

confidence: 91%

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

et al. 2020

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Deep brain stimulation (DBS) modulates the neuronal activity in specific brain circuits and has been recently considered as a promising intervention for refractory addiction. The insula cortex is the hub of interoception and is known to be involved in different aspects of substance use disorder. In the present study, we investigate the effects of continuous high frequency DBS in the anterior insula (AI) on drug-seeking behaviors and examined the molecular mechanisms of DBS action in morphine-addicted rats. Sprague-Dawley rats were trained to the morphine-conditioned place preference (CPP, day 1–8) followed by bilaterally implanted with DBS electrodes in the AI (Day 10) and recovery (Day 10–15). Continuous high-frequency (HF) -DBS (130 Hz, 150 μA, 90 μs) was applied during withdrawal (Day 16–30) or extinction sessions. CPP tests were conducted on days 16, 30, 40 during withdrawal session and several rats were used for proteomic analysis on day 30. Following the complete extinction, morphine-CPP was reinstated by a priming dose of morphine infusion (2 mg/kg). The open field and novel objective recognition tests were also performed to evaluate the DBS side effect on the locomotion and recognition memory. Continuous HF-DBS in the AI attenuated the expression of morphine-CPP post-withdrawal (Day 30), but morphine addictive behavior relapsed 10 days after the cessation of DBS (Day 40). Continuous HF-DBS reduced the period to full extinction of morphine-CPP and blocked morphine priming-induced recurrence of morphine addiction. HF-DBS in the AI had no obvious effect on the locomotor activity and novel objective recognition and did not cause anxiety-like behavior. In addition, our proteomic analysis identified eight morphine-regulated proteins in the AI and their expression levels were reversely changed by HF-DBS. Continuous HF-DBS in the bilateral anterior insula prevents the relapse of morphine place preference after withdrawal, facilitates its extinction, blocks the reinstatement induced by morphine priming and reverses the expression of morphine-regulated proteins. Our findings suggest that manipulation of insular activity by DBS could be a potential intervention to treat substance use disorder, although future research is warranted.

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Section: Discussionsupporting

confidence: 91%

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

et al. 2020

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“…We identified that latestage CLN3 -/mice, like several mouse models of AD, have a decrease in the absolute number of hippocampal SWRs, a physiologic oscillation important for memory consolidation (31)(32)(33). Identification of shared network features could motivate future studies of network-targeted therapies, which are under development for AD (45)(46)(47)(48), in CLN3 disease. Studies of hippocampal-mediated learning and memory in CLN3 -/mice across the life span are needed to fully characterize the impact of these network alterations.…”

Section: Discussionmentioning

confidence: 97%

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Ahrens‐Nicklas¹,

Tecedor²,

Hall³

et al. 2019

JCI Insight

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“…A previous study reported an increase in NPCs in the SVZ associated with subthalamic nuclei DBS in patients with Parkinson's disease 35 . Preclinical studies have also demonstrated anti-epilepsy effects, antidepressant/anxiolytic responses and memory improvements by DBS correlated with neurogenesis [36][37][38] . Even so, adult neurogenesis is very species-specific, and the occurrence of neurogenesis in humans needs more critical thinking.…”

Section: Discussionmentioning

confidence: 98%

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia

Sun

et al. 2020

Sci Rep

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Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

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Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

Cited by 48 publications

References 89 publications

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

Neuronal network dysfunction precedes storage and neurodegeneration in a lysosomal storage disorder

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia

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