fos expression
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2022 ◽  
Author(s):  
Adam Khalifa ◽  
Seyed Mahdi Abrishami ◽  
Mohsen Zaeimbashi ◽  
Alexander D. Tang ◽  
Brian Coughlin ◽  
...  

Non-invasive stimulation of deep brain regions has been a major goal for neuroscience and neuromodulation in the past three decades. Transcranial magnetic stimulation (TMS), for instance, cannot target deep regions in the brain without activating the overlying tissues and has a poor spatial resolution. In this manuscript, we propose a new concept that relies on the temporal interference of two high-frequency magnetic fields generated by two electromagnetic solenoids. To illustrate the concept, custom solenoids were fabricated and optimized to generate temporal interfering electric fields for rodent brain stimulation. C-Fos expression was used to track neuronal activation. C-Fos expression was not present in regions impacted by only one high-frequency magnetic field indicating ineffective recruitment of neural activity in non-target regions. In contrast, regions impacted by two fields that interfere to create a low-frequency envelope display a strong increase in c-Fos expression. Therefore, this magnetic temporal interference solenoid-based system provides a framework to perform further stimulation studies that would investigate the advantages it could bring over conventional TMS systems.


Foods ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 141
Author(s):  
Erin L. Wood ◽  
Sarah N. Gartner ◽  
Anica Klockars ◽  
Laura K. McColl ◽  
David G. Christian ◽  
...  

The natural 20:80 whey:casein ratio in cow’s milk (CM) for adults and infants is adjusted to reflect the 60:40 ratio of human milk, but the feeding and metabolic consequences of this adjustment have been understudied. In adult human subjects, the 60:40 CM differently affects glucose metabolism and hormone release than the 20:80 CM. In laboratory animals, whey-adapted goat’s milk is consumed in larger quantities. It is unknown whether whey enhancement of CM would have similar consequences on appetite and whether it would affect feeding-relevant brain regulatory mechanisms. In this set of studies utilizing laboratory mice, we found that the 60:40 CM was consumed more avidly than the 20:80 control formulation by animals motivated to eat by energy deprivation and by palatability (in the absence of hunger) and that this hyperphagia stemmed from prolongation of the meal. Furthermore, in two-bottle choice paradigms, whey-adapted CM was preferred against the natural 20:80 milk. The intake of the whey-adapted CM induced neuronal activation (assessed through analysis of c-Fos expression in neurons) in brain sites promoting satiation, but importantly, this activation was less pronounced than after ingestion of the natural 20:80 whey:casein CM. Activation of hypothalamic neurons synthesizing anorexigenic neuropeptide oxytocin (OT) was also less robust after the 60:40 CM intake than after the 20:80 CM. Pharmacological blockade of the OT receptor in mice led to an increase in the consumption only of the 20:80 CM, thus, of the milk that induced greater activation of OT neurons. We conclude that the whey-adapted CM is overconsumed compared to the natural 20:80 CM and that this overconsumption is associated with weakened responsiveness of central networks involved in satiety signalling, including OT.


2021 ◽  
Vol 15 ◽  
Author(s):  
Jackson Brougher ◽  
Umaymah Aziz ◽  
Nikitha Adari ◽  
Muskaan Chaturvedi ◽  
Aryela Jules ◽  
...  

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve.Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats.Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC).Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons.Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lingling Zhu ◽  
Yanxiu Wang ◽  
Xiaowen Lin ◽  
Xu Zhao ◽  
Zhi jian Fu

The effects of ozone on hippocampal expression levels of brain-derived neurotrophic factor (BDNF) and c-fos protein (Fos) were evaluated in rats with chronic compression of dorsal root ganglia (CCD). Forty-eight adult female Sprague-Dawley rats were randomly divided into the following 4 groups ( n = 12 ): sham operation (sham group), CCD group, CCD with 20 μg/ml of ozone ( CCD + A O 3 group), and CCD with 40 μg/ml of ozone ( CCD + B O 3 group). Except the sham group, unilateral L5 dorsal root ganglion (DRG) compression was performed on all other groups. On days 1, 2, and 4 after the operation, the CCD + A O 3 and CCD + B O 3 groups were injected with 100 μl of ozone with concentrations of 20 and 40 μg/ml, respectively. Thermal withdrawal latencies (TWLs) and mechanical withdrawal thresholds (MWTs) were measured at various time points before and after the operation. BDNF and Fos expressions were examined in the extracted hippocampi using immunohistochemistry. The TWLs and MWTs of CCD model rats that received ozone were lower with decreased BDNF and increased Fos expression levels, on day 21 after the operation, compared to those of the sham group ( P < 0.05 ). The TWLs and MWTs of the CCD + A O 3 and CCD + B O 3 groups were higher with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD group ( P < 0.05 ). The TWLs were longer and the MWTs were higher in the CCD + B O 3 group at each time point with increased BDNF and decreased Fos expression levels, on day 21 after the operation, compared to those of the CCD + A O 3 group ( P < 0.05 ). Our results revealed that ozone can relieve the neuropathic pain caused by the pathological neuralgia resulting from DRG compression in rats. The mechanism of action for ozone is likely associated with changes in BDNF and Fos expression levels in the hippocampus.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Chang-Rui Chen ◽  
Yu-Heng Zhong ◽  
Shan Jiang ◽  
Wei Xu ◽  
Lei Xiao ◽  
...  

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.


2021 ◽  
Author(s):  
◽  
Natasha Bukholt

<p>Background: MDMA preferentially releases serotonin (5HT) but following repeated exposure there is a decrease in this MDMA-produced effect. At the same time, some studies suggest an increase in MDMA-produced dopamine (DA) release following repeated exposure. The sensitised DA response is often accompanied by sensitisation of MDMA-produced locomotor activity. Because DAergic mechanisms have been implicated in the positively reinforcing properties of MDMA, these neuroadaptations might be relevant to MDMA self-administration.  Objectives: The main objective of this study was to determine whether MDMA self-administration and non-contingent MDMA exposure differentially affected the development of sensitisation to MDMA-produced hyperactivity. Additionally, the relationship between MDMA-produced hyperactivity and changes in c-fos expression in DA terminal regions was determined.  Methods: Triads of rats were designated ‘master’, ‘yoked MDMA’, or ‘yoked saline’. Lever press responding by the master rat resulted in an intravenous infusion of MDMA for both the master rat and the yoked MDMA rat, as well as an equal infusion of vehicle for the yoked control rat. Daily tests continued until a total of 350 mg/kg MDMA had been self-administered. Three days following the last self-administration session, forward and vertical locomotion produced by MDMA (5.0 mg/kg, i.p) were measured during a 2 hr test. Rats were sacrificed immediately following the behavioural test, and c-fos immunohistochemistry was measured.  Results: Repeated MDMA exposure resulted in sensitised forward and vertical locomotor activity. Sensitisation of the increase in forward locomotion was produced only in rats that self-administered MDMA; non-contingent MDMA administration failed to sensitise this behavioural response. In contrast, sensitisation to MDMA-produced vertical activity was produced following both contingent and non-contingent MDMA exposure. C-fos expression was reduced in ventrolateral, and ventromedial areas of the dorsal striatum, as well as the infralimbic cortex, after MDMA exposure, regardless of whether the exposure was via self-administration or yoked administration. A selective decrease in c-fos expression in the nucleus accumbens (NAc) core and the cingulate cortex was produced by MDMA self-administration. There was a negative correlation between MDMA-produced forward locomotor activity and MDMA-produced c-fos expression in the NAc core, cingulate cortex and infralimbic cortex. A negative correlation between rearing activity and MDMA-produced c-fos expression in the NAc core, NAc shell, cingulate cortex, and infralimbic cortex was also found.  Conclusions: These data provide evidence of behavioural sensitisation as a result of repeated MDMA exposure. Furthermore, MDMA-produced behavioural sensitisation was associated with a decrease in c-fos expression that was evident in the NAc and prefrontal cortex. Finally, region-specific changes in c-fos expression suggest an important role of neuroadaptations in the NAc core and the infralimbic cortex as a consequence of MDMA self-administration.</p>


2021 ◽  
Author(s):  
◽  
Hanna Squire

<p>Rationale: (±) 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) is a recreationally abused psychostimulant that leads to detrimental effects on memory performance. MDMA’s acute effects on memory are often attributed to a working memory impairment resulting from compromised serotonin systems. However, recent evidence from non-human animal experimental studies suggests that acute MDMA may impair memory performance through an MDMA-induced increase in dopamine (DA) release, leading to overstimulation of DA D1 receptors. The overstimulation of D1 receptors during acute MDMA exposure is thought to indirectly impair memory by increasing a subject’s susceptibility to proactive interference, leading to a perseverative pattern of responding during memory tasks.  Objective: This project investigates the hypothesis that acute MDMA impairs memory performance via overstimulation of D1 receptors. The acute actions of MDMA will be assessed using DA D1 mutant (DAD1-/-) rats which possess a selective down-regulation in functional DA D1 receptors. On the basis that acute MDMA impairs memory function via overstimulation of D1 receptors it is predicted that, compared to control rats, DAD1-/- rats will be protected from the acute memory deficits caused by MDMA. Due to the novelty of the DAD1-/- rat model, prior to the assessment of the acute effects of MDMA on memory performance in these rats, behavioural and neurochemical characterisations will be conducted.  Methods: Firstly, a behavioural characterisation was conducted to explore the tendencies of DAD1-/- rats, compared to controls, in a drug free state. Behaviours relevant for motivation and reward, movement, and memory were the focus of the behavioural investigation due to evidence suggesting a role for D1-like receptors in these functions. Secondly, a neurochemical assessment of DAD1-/- and controls rats in response to MDMA (3 mg/kg) was assayed using c-fos expression, a marker for neuronal activity, in several brain regions with known DA innervation. Thirdly, to assess the acute effects of MDMA on memory performance, DAD1-/- and control rats were trained on a spatial working memory T-maze task, delayed non-matching to position (DNMTP), over 25 sessions. Once trained, rats were administered either MDMA (1.5, 2.25 and 3 mg/kg) or saline fifteen minutes prior to testing on DNMTP, with all subjects experiencing all drug doses three time each. In addition, to further investigate the hypothesis that overstimulation of D1 receptors impairs memory performance, the effects of a D1 receptor agonist, SKF 81297 (0.5, 1, 1.5, 3, 4.5 mg/kg) on DNMTP performance were also assessed.  Results: The behavioural characterisation revealed that DAD1-/- rats are capable of performing many behaviours relevant for reward processing, movement and memory function. However, DAD1-/- rats were impaired with regard to some reward-related behaviours, such as the acquitision of lever pressing for sugar pellets. The assessment of c-fos expression demonstrated that DAD1-/- rats express less c-fos in the medial prefrontal cortex, striatum and nucleus accumbens compared to control rats following MDMA administration. Lastly, the effects of acute MDMA administration on memory performance were tested. During the third block of MDMA administration, control rats demonstrated decreased accuracy on the DMNTP task at both the 2.25 and 3 mg/kg doses. The decrease in accuracy during MDMA exposure in control rats was driven by an increase in perseverative errors. On the contrary, DAD1-/- rats were not impaired on the DNMTP task following acute MDMA at any of the doses tested. Administration of SKF 81297 did not lead to any systematic changes in performance, but at the 3 mg/kg dose DAD1-/- rats displayed increased accuracy compared to control rats.  Conclusions: DAD1-/- rats were protected from an MDMA-induced decrease in accuracy on the DNMTP task compared to control rats. This finding challenges the assumption that MDMA’s acute effects on memory performance are wholly due to serononergic mechanisms. Specifically, the current study provides evidence for the hypothesis that acute MDMA exposure impairs memory performance in rats.</p>


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