首页 > 最新文献

Frontiers in Neural Circuits最新文献

英文 中文
The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease. 在双侧帕金森大鼠模型中,5 -羟色胺投射通路对左旋多巴诱导的运动障碍和精神病的化学发生作用。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-14 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1463941
Natalie Lipari, Ashley Galfano, Shruti Venkatesh, Han Grezenko, Ivette M Sandoval, Fredric P Manfredsson, Christopher Bishop

Introduction: Parkinson's disease (PD) is commonly characterized by severe dopamine (DA) depletion within the substantia nigra (SN) leading to a myriad of motor and non-motor symptoms. One underappreciated and prevalent non-motor symptom, Parkinson's disease-associated psychosis (PDAP), significantly erodes patient and caregiver quality of life yet remains vastly understudied. While the gold standard pharmacotherapy for motor symptoms Levodopa (LD) is initially highly effective, it can lead to motor fluctuations like LD-induced dyskinesia (LID) and non-motor fluctuations such as intermittent PDAP. One source of these fluctuations could be the serotonergic raphe nuclei and their projections. Serotonin (5-HT) neurons possess the machinery necessary to convert and release DA from exogenous LD. In DA-depleted brain regions these 5-HT projections can act as surrogates to the DA system initially compensating but chronically leading to aberrant neuroplasticity which has been linked to LID and may also contribute to non-motor fluctuations. In support, recent work from our lab established a positive relationship between LID and PDAP in parkinsonian rats. Therefore, it was hypothesized that normalizing 5-HT forebrain input would reduce the co-expression of LID and PDAP.

Methods: To do so, we expressed 5-HT projection specific inhibitory designer receptor exclusively activated by designer drugs (DREADDs) using Cre-dependent AAV9-hM4di in tryptophan hydroxylase 2 (TPH2)-Cre bilaterally 6-OHDA-lesioned rats. Thereafter we used the designer drug Compound 21 to selectively inhibit 5-HT raphe projections during LD treatment to modulate the expression of PDAP, assayed by prepulse inhibition (PPI) and LID, quantified by the abnormal involuntary movements (AIMs) test.

Results: Our results suggest that chemogenetic inhibition of 5-HT raphe-projecting cells significantly reduces LID without affecting stepping ability or established sensorimotor gating deficits.

Discussion: Overall, this study provides further evidence for the complex influence of 5-HT raphe-projecting neurons on LD's neurobehavioral effects.

简介:帕金森病(PD)的常见特征是黑质(SN)内多巴胺(DA)严重耗损,导致无数的运动和非运动症状。帕金森氏病相关精神病(PDAP)是一种未被充分认识和普遍存在的非运动症状,它显著地侵蚀了患者和护理者的生活质量,但研究还远远不够。虽然左旋多巴(LD)运动症状的金标准药物治疗最初非常有效,但它可能导致运动波动,如LD诱导的运动障碍(LID)和非运动波动,如间歇性PDAP。这些波动的一个来源可能是血清素能中叶核及其投射。5-羟色胺(5-HT)神经元拥有从外源性LD转化和释放DA所必需的机制。在DA耗竭的大脑区域,这些5-HT投射可以替代DA系统,最初进行补偿,但长期导致与LID相关的异常神经可塑性,并可能导致非运动波动。为了支持这一点,我们实验室最近的工作在帕金森大鼠中建立了LID和PDAP之间的正相关关系。因此,我们假设正常的5-HT前脑输入会减少LID和PDAP的共表达。方法:利用cre依赖性AAV9-hM4di在双侧6- ohda损伤大鼠的色氨酸羟化酶2 (TPH2)-Cre中表达由设计药物独占激活的5-HT投射特异性抑制设计物受体(DREADDs)。随后,我们使用设计药物化合物21在LD治疗期间选择性抑制5-HT中缝突起,以调节PDAP的表达,通过脉冲前抑制(PPI)和LID进行检测,通过异常不自主运动(AIMs)测试进行量化。结果:我们的研究结果表明,化学发生抑制5-HT纹突细胞可显著降低LID,而不会影响步进能力或建立感觉运动门控缺陷。讨论:总的来说,本研究进一步证明了5-HT图投射神经元对LD神经行为效应的复杂影响。
{"title":"The effects of chemogenetic targeting of serotonin-projecting pathways on L-DOPA-induced dyskinesia and psychosis in a bilateral rat model of Parkinson's disease.","authors":"Natalie Lipari, Ashley Galfano, Shruti Venkatesh, Han Grezenko, Ivette M Sandoval, Fredric P Manfredsson, Christopher Bishop","doi":"10.3389/fncir.2024.1463941","DOIUrl":"10.3389/fncir.2024.1463941","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) is commonly characterized by severe dopamine (DA) depletion within the substantia nigra (SN) leading to a myriad of motor and non-motor symptoms. One underappreciated and prevalent non-motor symptom, Parkinson's disease-associated psychosis (PDAP), significantly erodes patient and caregiver quality of life yet remains vastly understudied. While the gold standard pharmacotherapy for motor symptoms Levodopa (LD) is initially highly effective, it can lead to motor fluctuations like LD-induced dyskinesia (LID) and non-motor fluctuations such as intermittent PDAP. One source of these fluctuations could be the serotonergic raphe nuclei and their projections. Serotonin (5-HT) neurons possess the machinery necessary to convert and release DA from exogenous LD. In DA-depleted brain regions these 5-HT projections can act as surrogates to the DA system initially compensating but chronically leading to aberrant neuroplasticity which has been linked to LID and may also contribute to non-motor fluctuations. In support, recent work from our lab established a positive relationship between LID and PDAP in parkinsonian rats. Therefore, it was hypothesized that normalizing 5-HT forebrain input would reduce the co-expression of LID and PDAP.</p><p><strong>Methods: </strong>To do so, we expressed 5-HT projection specific inhibitory designer receptor exclusively activated by designer drugs (DREADDs) using Cre-dependent AAV9-hM4di in tryptophan hydroxylase 2 (TPH2)-Cre bilaterally 6-OHDA-lesioned rats. Thereafter we used the designer drug Compound 21 to selectively inhibit 5-HT raphe projections during LD treatment to modulate the expression of PDAP, assayed by prepulse inhibition (PPI) and LID, quantified by the abnormal involuntary movements (AIMs) test.</p><p><strong>Results: </strong>Our results suggest that chemogenetic inhibition of 5-HT raphe-projecting cells significantly reduces LID without affecting stepping ability or established sensorimotor gating deficits.</p><p><strong>Discussion: </strong>Overall, this study provides further evidence for the complex influence of 5-HT raphe-projecting neurons on LD's neurobehavioral effects.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1463941"},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Specific structural changes in Parkinson's disease-related olfactory dysfunction compared to others forms of olfactory dysfunction. 与其他形式的嗅觉功能障碍相比,帕金森病相关嗅觉功能障碍的特殊结构变化。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1503841
Sarah Brosse, Cécilia Tremblay, Inés Mérida, Johannes Frasnelli
{"title":"Specific structural changes in Parkinson's disease-related olfactory dysfunction compared to others forms of olfactory dysfunction.","authors":"Sarah Brosse, Cécilia Tremblay, Inés Mérida, Johannes Frasnelli","doi":"10.3389/fncir.2024.1503841","DOIUrl":"10.3389/fncir.2024.1503841","url":null,"abstract":"","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1503841"},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synaptic plasticity and roles of orexin in distinct domains of the olfactory tubercle. 嗅结节不同区域的突触可塑性和奥曲肽的作用
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-07 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1473403
Sajib Podder, Yoshihiro Murata, Mutsuo Taniguchi, Shogo Shimizu, Masahiro Yamaguchi

Olfactory behavior is highly plastic, and the olfactory tubercle (OT), a component of the olfactory cortex and ventral striatum, includes anteromedial (amOT) and lateral (lOT) domains with roles in attractive and aversive olfactory behavioral learning, respectively. However, the underlying properties of synaptic plasticity in these domains are incompletely understood. Synaptic plasticity is regulated by multiple signals including synaptic inputs and neuromodulators. Interestingly, the amOT domain exhibits high expression of various receptors for neuromodulators. We investigated synaptic plasticity in mouse OT slices by combining electrical stimulation and treatment with the appetite-promoting neuropeptide orexin, the receptors of which are highly expressed in the amOT. In both the amOT and lOT, one round of 2-Hz burst stimulation elicited short-term potentiation of the field excitatory postsynaptic potential, whereas three rounds of stimulation induced long-term potentiation (LTP) that persisted for 150 min. In the amOT, orexin-A induced LTP was blocked by the orexin receptor type 1 antagonist SB334867. Orexin-A also facilitated LTP induction in the amOT by one round of 2-Hz burst stimulation. By contrast, these effects were not observed in the lOT. These results highlighted the similarity and difference in synaptic plasticity between the OT domains and suggested that orexin facilitates synaptic plasticity in the amOT during olfactory learning processes such as food odor learning.

嗅觉行为具有高度可塑性,而嗅小管(OT)是嗅觉皮层和腹侧纹状体的组成部分,包括前内侧(amOT)和外侧(lOT)结构域,分别在吸引性和厌恶性嗅觉行为学习中发挥作用。然而,人们对这些结构域中突触可塑性的基本特性尚不完全了解。突触可塑性受多种信号调控,包括突触输入和神经调节剂。有趣的是,amOT 结构域中各种神经调节剂受体的表达量很高。我们通过电刺激和促进食欲的神经肽奥曲肽处理(其受体在 amOT 中高表达),研究了小鼠 OT 切片的突触可塑性。在amOT和lOT中,一轮2赫兹的猝发刺激可引起场兴奋性突触后电位的短期电位,而三轮刺激可诱导持续150分钟的长期电位(LTP)。在 amOT 中,奥曲肽受体 1 型拮抗剂 SB334867 可阻断奥曲肽-A 诱导的 LTP。奥曲肽-A还能通过一轮2赫兹的猝发刺激促进amOT的LTP诱导。相比之下,在lOT中没有观察到这些效应。这些结果突显了OT域之间突触可塑性的异同,并表明奥曲肽在嗅觉学习过程(如食物气味学习)中促进了amOT的突触可塑性。
{"title":"Synaptic plasticity and roles of orexin in distinct domains of the olfactory tubercle.","authors":"Sajib Podder, Yoshihiro Murata, Mutsuo Taniguchi, Shogo Shimizu, Masahiro Yamaguchi","doi":"10.3389/fncir.2024.1473403","DOIUrl":"10.3389/fncir.2024.1473403","url":null,"abstract":"<p><p>Olfactory behavior is highly plastic, and the olfactory tubercle (OT), a component of the olfactory cortex and ventral striatum, includes anteromedial (amOT) and lateral (lOT) domains with roles in attractive and aversive olfactory behavioral learning, respectively. However, the underlying properties of synaptic plasticity in these domains are incompletely understood. Synaptic plasticity is regulated by multiple signals including synaptic inputs and neuromodulators. Interestingly, the amOT domain exhibits high expression of various receptors for neuromodulators. We investigated synaptic plasticity in mouse OT slices by combining electrical stimulation and treatment with the appetite-promoting neuropeptide orexin, the receptors of which are highly expressed in the amOT. In both the amOT and lOT, one round of 2-Hz burst stimulation elicited short-term potentiation of the field excitatory postsynaptic potential, whereas three rounds of stimulation induced long-term potentiation (LTP) that persisted for 150 min. In the amOT, orexin-A induced LTP was blocked by the orexin receptor type 1 antagonist SB334867. Orexin-A also facilitated LTP induction in the amOT by one round of 2-Hz burst stimulation. By contrast, these effects were not observed in the lOT. These results highlighted the similarity and difference in synaptic plasticity between the OT domains and suggested that orexin facilitates synaptic plasticity in the amOT during olfactory learning processes such as food odor learning.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1473403"},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor density underlies intraregional and interregional functional centrality. α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体密度是区域内和区域间功能中心性的基础。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1497897
Taisuke Yatomi, Dardo Tomasi, Hideaki Tani, Shinichiro Nakajima, Sakiko Tsugawa, Nobuhiro Nagai, Teruki Koizumi, Waki Nakajima, Mai Hatano, Hiroyuki Uchida, Takuya Takahashi

Local and global functional connectivity densities (lFCD and gFCD, respectively), derived from functional magnetic resonance imaging (fMRI) data, represent the degree of functional centrality within local and global brain networks. While these methods are well-established for mapping brain connectivity, the molecular and synaptic foundations of these connectivity patterns remain unclear. Glutamate, the principal excitatory neurotransmitter in the brain, plays a key role in these processes. Among its receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is crucial for neurotransmission, particularly in cognitive functions such as learning and memory. This study aimed to examine the association of the AMPAR density and FCD metrics of intraregional and interregional functional centrality. Using [11C]K-2, a positron emission tomography (PET) tracer specific for AMPARs, we measured AMPAR density in the brains of 35 healthy participants. Our findings revealed a strong positive correlation between AMPAR density and both lFCD and gFCD-lFCD across the entire brain. This correlation was especially notable in key regions such as the anterior cingulate cortex, posterior cingulate cortex, pre-subgenual frontal cortex, Default Mode Network, and Visual Network. These results highlight that postsynaptic AMPARs significantly contribute to both local and global functional connectivity in the brain, particularly in network hub regions. This study provides valuable insights into the molecular and synaptic underpinnings of brain functional connectomes.

根据功能磁共振成像(fMRI)数据得出的局部和全局功能连通性密度(lFCD 和 gFCD)代表了局部和全局大脑网络中的功能中心程度。虽然这些方法在绘制大脑连接图方面已得到广泛认可,但这些连接模式的分子和突触基础仍不清楚。谷氨酸是大脑中主要的兴奋性神经递质,在这些过程中起着关键作用。在其受体中,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)对神经传递,尤其是学习和记忆等认知功能至关重要。本研究旨在考察 AMPAR 密度与 FCD 区域内和区域间功能中心性指标之间的关联。我们使用针对 AMPAR 的正电子发射断层扫描(PET)示踪剂 [11C]K-2 测量了 35 名健康参与者大脑中的 AMPAR 密度。我们的研究结果表明,在整个大脑中,AMPAR 密度与 lFCD 和 gFCD-lFCD 之间存在很强的正相关性。这种相关性在前扣带回皮层、后扣带回皮层、前下额叶皮层、默认模式网络和视觉网络等关键区域尤为明显。这些结果突显了突触后 AMPARs 对大脑局部和全局功能连接的重要贡献,尤其是在网络枢纽区域。这项研究为了解大脑功能连接组的分子和突触基础提供了宝贵的见解。
{"title":"<i>α</i>-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor density underlies intraregional and interregional functional centrality.","authors":"Taisuke Yatomi, Dardo Tomasi, Hideaki Tani, Shinichiro Nakajima, Sakiko Tsugawa, Nobuhiro Nagai, Teruki Koizumi, Waki Nakajima, Mai Hatano, Hiroyuki Uchida, Takuya Takahashi","doi":"10.3389/fncir.2024.1497897","DOIUrl":"10.3389/fncir.2024.1497897","url":null,"abstract":"<p><p>Local and global functional connectivity densities (lFCD and gFCD, respectively), derived from functional magnetic resonance imaging (fMRI) data, represent the degree of functional centrality within local and global brain networks. While these methods are well-established for mapping brain connectivity, the molecular and synaptic foundations of these connectivity patterns remain unclear. Glutamate, the principal excitatory neurotransmitter in the brain, plays a key role in these processes. Among its receptors, the <i>α</i>-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is crucial for neurotransmission, particularly in cognitive functions such as learning and memory. This study aimed to examine the association of the AMPAR density and FCD metrics of intraregional and interregional functional centrality. Using [<sup>11</sup>C]K-2, a positron emission tomography (PET) tracer specific for AMPARs, we measured AMPAR density in the brains of 35 healthy participants. Our findings revealed a strong positive correlation between AMPAR density and both lFCD and gFCD-lFCD across the entire brain. This correlation was especially notable in key regions such as the anterior cingulate cortex, posterior cingulate cortex, pre-subgenual frontal cortex, Default Mode Network, and Visual Network. These results highlight that postsynaptic AMPARs significantly contribute to both local and global functional connectivity in the brain, particularly in network hub regions. This study provides valuable insights into the molecular and synaptic underpinnings of brain functional connectomes.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1497897"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nature and nurture in fruit fly hearing. 果蝇听力的天性与教养
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1503438
Azusa Kamikouchi, Xiaodong Li

As for human language learning and birdsong acquisition, fruit flies adjust their auditory perception based on past sound experiences. This phenomenon is known as song preference learning in flies. Recent advancements in omics databases, such as the single-cell transcriptome and brain connectomes, have been integrated into traditional molecular genetics, making the fruit fly an outstanding model for studying the neural basis of "Nature and Nurture" in auditory perception and behaviors. This minireview aims to provide an overview of song preference in flies, including the nature of the phenomenon and its underlying neural mechanisms. Specifically, we focus on the neural circuitry involved in song preference learning, with which auditory experiences shape the song preference of flies. This shaping process depends on an integration hub that processes external sensory stimuli and internal states to enable flexible control of behavior. We also briefly review recent findings on the signals that feed into this integration hub, modulating song preference of flies in an experience-dependent manner.

与人类的语言学习和鸟鸣习得一样,果蝇也会根据以往的声音经验调整自己的听觉感知。这种现象被称为果蝇的歌曲偏好学习。近年来,单细胞转录组和脑连接组等全局数据库的发展已与传统的分子遗传学相结合,使果蝇成为研究听觉感知和行为中 "自然与天赋 "神经基础的杰出模型。本微综述旨在概述果蝇的鸣唱偏好,包括该现象的本质及其潜在的神经机制。具体而言,我们将重点关注参与鸣唱偏好学习的神经回路,即听觉经验对苍蝇鸣唱偏好的塑造过程。这种塑造过程依赖于处理外部感官刺激和内部状态的整合中枢,从而实现对行为的灵活控制。我们还简要回顾了有关信号的最新研究成果,这些信号进入这个整合中枢,以依赖经验的方式调节苍蝇的鸣唱偏好。
{"title":"Nature and nurture in fruit fly hearing.","authors":"Azusa Kamikouchi, Xiaodong Li","doi":"10.3389/fncir.2024.1503438","DOIUrl":"10.3389/fncir.2024.1503438","url":null,"abstract":"<p><p>As for human language learning and birdsong acquisition, fruit flies adjust their auditory perception based on past sound experiences. This phenomenon is known as song preference learning in flies. Recent advancements in omics databases, such as the single-cell transcriptome and brain connectomes, have been integrated into traditional molecular genetics, making the fruit fly an outstanding model for studying the neural basis of \"Nature and Nurture\" in auditory perception and behaviors. This minireview aims to provide an overview of song preference in flies, including the nature of the phenomenon and its underlying neural mechanisms. Specifically, we focus on the neural circuitry involved in song preference learning, with which auditory experiences shape the song preference of flies. This shaping process depends on an integration hub that processes external sensory stimuli and internal states to enable flexible control of behavior. We also briefly review recent findings on the signals that feed into this integration hub, modulating song preference of flies in an experience-dependent manner.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1503438"},"PeriodicalIF":3.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alpha-2 nicotinic acetylcholine receptors regulate spectral integration in auditory cortex. α-2烟碱乙酰胆碱受体调节听觉皮层的频谱整合。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1492452
Irakli Intskirveli, Susan Gil, Ronit Lazar, Raju Metherate

Introduction: In primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)-inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance ("horizontal") projections to multiple layers carrying information about spectrally distant ("nonCF") stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to "sharpen" RFs-to increase gain within a narrowed RF-resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.

Methods: Here, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.

Results: The distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.

Discussion: The results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.

简介:在初级听觉皮层(A1)中,含有α2亚单位的烟碱乙酰胆碱受体(nAChRs)表达于第5层的马蒂诺蒂细胞(Martinotti cells,MCs)--抑制性中间神经元,MCs将主轴突发送到浅层,以抑制锥体细胞(PCs)的远端顶端树突。MCs 还与上釉层的中间神经元联系,而上釉层的中间神经元反过来又抑制 PCs。因此,MC 可分别通过抑制和解除抑制远端和近端顶端树突来调节 PC。PC的听觉输入包括丘脑皮层输入到中层的特征频率(CF)和近CF刺激信息,以及皮层内长距离("水平")投射到多层的光谱遥远("非CF")刺激信息。CF和非CF输入整合成宽频感受野(RF)。全身注射尼古丁可激活 nAChRs,使射频 "锐化"--在缩小的射频范围内增加增益--从而增强对 CF 刺激的反应,降低对非 CF 刺激的反应。方法:我们在荧光标记了α2 nAChR表达神经元的小鼠和基因上删除了α2 nAChR的小鼠中研究了α2 nAChR的作用:听皮层中荧光神经元的分布与之前的研究一致,表明第 5 层 MC 中存在 α2 nAChRs,包括第 5 层的非锥体体细胞和第 1 层的致密过程。我们还在皮层下听觉区域观察到了标记,包括内侧膝状体的过程,但没有体节,以及下丘的纤维和体节。通过对α2 nAChR基因敲除小鼠的电生理(电流源密度)记录,我们发现全身性尼古丁不能增强第4层的CF诱发输入,这表明皮层下的α2 nAChRs起了作用,并且不能减少非CF诱发反应,这表明α2 nAChRs调节水平投射以产生RF缩小:讨论:研究结果支持α2 nAChRs在A1中同时增强射频增益和缩小射频宽度的假设。值得注意的是,类似的神经回路可能在整个大脑皮层和海马中反复出现,这表明α2 nAChRs调节的功能是广泛保守的。
{"title":"Alpha-2 nicotinic acetylcholine receptors regulate spectral integration in auditory cortex.","authors":"Irakli Intskirveli, Susan Gil, Ronit Lazar, Raju Metherate","doi":"10.3389/fncir.2024.1492452","DOIUrl":"10.3389/fncir.2024.1492452","url":null,"abstract":"<p><strong>Introduction: </strong>In primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)-inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance (\"horizontal\") projections to multiple layers carrying information about spectrally distant (\"nonCF\") stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to \"sharpen\" RFs-to increase gain within a narrowed RF-resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.</p><p><strong>Methods: </strong>Here, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.</p><p><strong>Results: </strong>The distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.</p><p><strong>Discussion: </strong>The results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1492452"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dialectics of perisomatic inhibition-The unity and conflict of opposites. 周身抑制的辩证法--对立面的统一与冲突。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1494300
Andrei Rozov, David John Jappy, Ksenia Maltseva, Alina Vazetdinova, Fliza Valiullina-Rakhmatullina

Over the past three decades, a great deal of attention has been paid to the study of perisomatic inhibition and perisomatic inhibitory basket cells. A growing body of experimental evidence points to the leading role of perisomatic inhibitory cells in the generation of oscillatory activity in various frequency ranges. Recently the link between the activity of basket cells and complex behavior has been demonstrated in several laboratories. However, all this is true only for one type of perisomatic inhibitory interneuron-parvalbumin-positive basket cells. Nevertheless, where parvalbumin-positive basket cells are found, there is another type of basket cell, cholecystokinin-positive interneurons. These two types of interneurons share a number of common features: they innervate the same compartments of target neurons and they often receive excitation from the same sources, but they also differ from each other in the synchrony of their GABA release and expression of receptors. The functional role of cholecystokinin-positive basket cells in oscillatory activity is not so obvious. They were thought to be involved in theta oscillations, however recent measurements in free moving animals have put some doubts on this hypothesis. Therefore, an important question is, whether these two types of basket cells work synergistically or perform opposing actions in functional networks? In this mini-review, we attempt to answer this question by putting forward the idea that these two types of basket cells are functionally united as two entities of the same network, and their opposing actions are necessary to maintain rhythmogenesis in a "healthy", physiological range.

在过去的三十年中,人们一直非常关注对同膜周围抑制和同膜周围抑制性篮状细胞的研究。越来越多的实验证据表明,在产生各种频率范围的振荡活动中,嗜周抑制细胞起着主导作用。最近,一些实验室证实了篮状细胞的活动与复杂行为之间的联系。然而,所有这一切都只适用于一种周围抑制性中间神经元--副发光素阳性篮状细胞。然而,在发现副发光素阳性篮状细胞的地方,还有另一类篮状细胞,即胆囊收缩素阳性中间神经元。这两类中间神经元有许多共同点:它们支配靶神经元的相同区室,而且经常接受来自相同来源的兴奋,但它们在 GABA 释放的同步性和受体表达方面也有所不同。胆囊收缩素阳性的篮状细胞在振荡活动中的功能作用并不明显。人们认为它们参与了θ振荡,但最近在自由活动的动物身上进行的测量对这一假设提出了一些质疑。因此,一个重要的问题是,在功能网络中,这两种类型的篮状细胞是协同工作还是发挥相反的作用?在这篇微型综述中,我们试图回答这个问题,我们提出的观点是,这两类篮状细胞在功能上是作为同一网络的两个实体结合在一起的,它们的对立作用是将节律发生维持在 "健康 "生理范围内的必要条件。
{"title":"Dialectics of perisomatic inhibition-The unity and conflict of opposites.","authors":"Andrei Rozov, David John Jappy, Ksenia Maltseva, Alina Vazetdinova, Fliza Valiullina-Rakhmatullina","doi":"10.3389/fncir.2024.1494300","DOIUrl":"https://doi.org/10.3389/fncir.2024.1494300","url":null,"abstract":"<p><p>Over the past three decades, a great deal of attention has been paid to the study of perisomatic inhibition and perisomatic inhibitory basket cells. A growing body of experimental evidence points to the leading role of perisomatic inhibitory cells in the generation of oscillatory activity in various frequency ranges. Recently the link between the activity of basket cells and complex behavior has been demonstrated in several laboratories. However, all this is true only for one type of perisomatic inhibitory interneuron-parvalbumin-positive basket cells. Nevertheless, where parvalbumin-positive basket cells are found, there is another type of basket cell, cholecystokinin-positive interneurons. These two types of interneurons share a number of common features: they innervate the same compartments of target neurons and they often receive excitation from the same sources, but they also differ from each other in the synchrony of their GABA release and expression of receptors. The functional role of cholecystokinin-positive basket cells in oscillatory activity is not so obvious. They were thought to be involved in theta oscillations, however recent measurements in free moving animals have put some doubts on this hypothesis. Therefore, an important question is, whether these two types of basket cells work synergistically or perform opposing actions in functional networks? In this mini-review, we attempt to answer this question by putting forward the idea that these two types of basket cells are functionally united as two entities of the same network, and their opposing actions are necessary to maintain rhythmogenesis in a \"healthy\", physiological range.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1494300"},"PeriodicalIF":3.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of orientation encoding across layers within single columns of primate V1 revealed by high-density recordings. 高密度记录显示的灵长类 V1 单列内各层方位编码的比较。
IF 3.4 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI: 10.3389/fncir.2024.1399571
Shude Zhu, Ruobing Xia, Xiaomo Chen, Tirin Moore

Primary visual cortex (V1) has been the focus of extensive neurophysiological investigations, with its laminar organization serving as a crucial model for understanding the functional logic of neocortical microcircuits. Utilizing newly developed high-density, Neuropixels probes, we measured visual responses from large populations of simultaneously recorded neurons distributed across layers of macaque V1. Within single recordings, myriad differences in the functional properties of neuronal subpopulations could be observed. Notably, while standard measurements of orientation selectivity showed only minor differences between laminar compartments, decoding stimulus orientation from layer 4C responses outperformed both superficial and deep layers within the same cortical column. The superior orientation discrimination within layer 4C was associated with greater response reliability of individual neurons rather than lower correlated activity within neuronal populations. Our results underscore the efficacy of high-density electrophysiology in revealing the functional organization and network properties of neocortical microcircuits within single experiments.

初级视觉皮层(V1)是大量神经生理学研究的焦点,它的层状组织是了解新皮层微电路功能逻辑的重要模型。利用新开发的高密度 Neuropixels 探头,我们测量了分布在猕猴 V1 各层的大量同时记录神经元群的视觉反应。在单次记录中,可以观察到神经元亚群功能特性的无数差异。值得注意的是,虽然方向选择性的标准测量结果表明层区之间的差异很小,但从第 4C 层的反应中解码刺激方向的能力却优于同一皮层柱中的浅层和深层。第 4C 层卓越的方向辨别力与单个神经元更高的响应可靠性有关,而不是与神经元群内更低的相关活动有关。我们的研究结果强调了高密度电生理学在单次实验中揭示新皮层微电路的功能组织和网络特性的功效。
{"title":"Comparison of orientation encoding across layers within single columns of primate V1 revealed by high-density recordings.","authors":"Shude Zhu, Ruobing Xia, Xiaomo Chen, Tirin Moore","doi":"10.3389/fncir.2024.1399571","DOIUrl":"https://doi.org/10.3389/fncir.2024.1399571","url":null,"abstract":"<p><p>Primary visual cortex (V1) has been the focus of extensive neurophysiological investigations, with its laminar organization serving as a crucial model for understanding the functional logic of neocortical microcircuits. Utilizing newly developed high-density, Neuropixels probes, we measured visual responses from large populations of simultaneously recorded neurons distributed across layers of macaque V1. Within single recordings, myriad differences in the functional properties of neuronal subpopulations could be observed. Notably, while standard measurements of orientation selectivity showed only minor differences between laminar compartments, decoding stimulus orientation from layer 4C responses outperformed both superficial and deep layers within the same cortical column. The superior orientation discrimination within layer 4C was associated with greater response reliability of individual neurons rather than lower correlated activity within neuronal populations. Our results underscore the efficacy of high-density electrophysiology in revealing the functional organization and network properties of neocortical microcircuits within single experiments.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1399571"},"PeriodicalIF":3.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11456443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Criticality and universality in neuronal cultures during “up” and “down” states 神经元培养在 "上升 "和 "下降 "状态下的临界性和普遍性
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-09-10 DOI: 10.3389/fncir.2024.1456558
Mohammad Yaghoubi, Javier G. Orlandi, Michael A. Colicos, Jörn Davidsen
The brain can be seen as a self-organized dynamical system that optimizes information processing and storage capabilities. This is supported by studies across scales, from small neuronal assemblies to the whole brain, where neuronal activity exhibits features typically associated with phase transitions in statistical physics. Such a critical state is characterized by the emergence of scale-free statistics as captured, for example, by the sizes and durations of activity avalanches corresponding to a cascading process of information flow. Another phenomenon observed during sleep, under anesthesia, and in in vitro cultures, is that cortical and hippocampal neuronal networks alternate between “up” and “down” states characterized by very distinct firing rates. Previous theoretical work has been able to relate these two concepts and proposed that only up states are critical whereas down states are subcritical, also indicating that the brain spontaneously transitions between the two. Using high-speed high-resolution calcium imaging recordings of neuronal cultures, we test this hypothesis here by analyzing the neuronal avalanche statistics in populations of thousands of neurons during “up” and “down” states separately. We find that both “up” and “down” states can exhibit scale-free behavior when taking into account their intrinsic time scales. In particular, the statistical signature of “down” states is indistinguishable from those observed previously in cultures without “up” states. We show that such behavior can not be explained by network models of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression, even when realistic noise levels, spatial network embeddings, and heterogeneous populations are taken into account, which instead exhibits behavior consistent with previous theoretical models. Similar differences were also observed when taking into consideration finite-size scaling effects, suggesting that the intrinsic dynamics and self-organization mechanisms of these cultures might be more complex than previously thought. In particular, our findings point to the existence of different mechanisms of neuronal communication, with different time scales, acting during either high-activity or low-activity states, potentially requiring different plasticity mechanisms.
大脑可以被视为一个自组织的动态系统,它能优化信息处理和存储能力。从小型神经元集合到整个大脑的跨尺度研究都证明了这一点,在这些研究中,神经元活动表现出与统计物理学中的相变相关的典型特征。这种临界状态的特征是无尺度统计的出现,例如,信息流级联过程所对应的活动雪崩的大小和持续时间。在睡眠、麻醉和体外培养过程中观察到的另一个现象是,大脑皮层和海马神经元网络会在 "上升 "和 "下降 "状态之间交替,这两种状态的特点是发射率截然不同。以前的理论研究能够将这两个概念联系起来,并提出只有 "上升 "状态才是临界状态,而 "下降 "状态则是亚临界状态,这也表明大脑会自发地在这两种状态之间转换。利用对神经元培养物的高速高分辨率钙成像记录,我们分别分析了数千个神经元群体在 "上升 "和 "下降 "状态下的神经元雪崩统计,从而验证了这一假设。我们发现,如果考虑到其内在时间尺度,"上升 "和 "下降 "状态都可以表现出无标度行为。特别是,"下行 "状态的统计特征与之前在没有 "上行 "状态的培养物中观察到的特征没有区别。我们的研究表明,即使考虑到现实的噪声水平、空间网络嵌入和异质种群,这种行为也无法用具有短期突触抑制的非保守性漏整合-发射神经元网络模型来解释,而表现出与以前的理论模型一致的行为。当考虑到有限尺寸缩放效应时,也观察到了类似的差异,这表明这些培养物的内在动力学和自组织机制可能比以前认为的更为复杂。特别是,我们的研究结果表明,在高活性或低活性状态下,存在不同时间尺度的神经元交流机制,可能需要不同的可塑性机制。
{"title":"Criticality and universality in neuronal cultures during “up” and “down” states","authors":"Mohammad Yaghoubi, Javier G. Orlandi, Michael A. Colicos, Jörn Davidsen","doi":"10.3389/fncir.2024.1456558","DOIUrl":"https://doi.org/10.3389/fncir.2024.1456558","url":null,"abstract":"The brain can be seen as a self-organized dynamical system that optimizes information processing and storage capabilities. This is supported by studies across scales, from small neuronal assemblies to the whole brain, where neuronal activity exhibits features typically associated with phase transitions in statistical physics. Such a critical state is characterized by the emergence of scale-free statistics as captured, for example, by the sizes and durations of activity avalanches corresponding to a cascading process of information flow. Another phenomenon observed during sleep, under anesthesia, and in <jats:italic>in vitro</jats:italic> cultures, is that cortical and hippocampal neuronal networks alternate between “up” and “down” states characterized by very distinct firing rates. Previous theoretical work has been able to relate these two concepts and proposed that only up states are critical whereas down states are subcritical, also indicating that the brain spontaneously transitions between the two. Using high-speed high-resolution calcium imaging recordings of neuronal cultures, we test this hypothesis here by analyzing the neuronal avalanche statistics in populations of thousands of neurons during “up” and “down” states separately. We find that both “up” and “down” states can exhibit scale-free behavior when taking into account their intrinsic time scales. In particular, the statistical signature of “down” states is indistinguishable from those observed previously in cultures without “up” states. We show that such behavior can not be explained by network models of non-conservative leaky integrate-and-fire neurons with short-term synaptic depression, even when realistic noise levels, spatial network embeddings, and heterogeneous populations are taken into account, which instead exhibits behavior consistent with previous theoretical models. Similar differences were also observed when taking into consideration finite-size scaling effects, suggesting that the intrinsic dynamics and self-organization mechanisms of these cultures might be more complex than previously thought. In particular, our findings point to the existence of different mechanisms of neuronal communication, with different time scales, acting during either high-activity or low-activity states, potentially requiring different plasticity mechanisms.","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"28 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L-methionine and the L-type Ca2+ channel agonist BAY K 8644 collaboratively contribute to the reduction of depressive-like behavior in mice L-蛋氨酸和 L 型 Ca2+ 通道激动剂 BAY K 8644 共同有助于减少小鼠的抑郁样行为
IF 3.5 3区 医学 Q2 NEUROSCIENCES Pub Date : 2024-08-29 DOI: 10.3389/fncir.2024.1435507
Ershu He, Ruixue Ma, Shanglan Qu, Xiaoye Zheng, Xin Peng, Jieyu Ji, Wenhao Ma, Xueyan Zhang, Ying Li, Hanwei Li, Yanjiao Li, Lijuan Li, Zhiting Gong
The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.
L 型钙离子通道(LTCC,又称 Cav1,2)参与调控神经元的关键功能,如树突信息整合、细胞存活和神经元基因表达。临床研究表明,L 型钙通道与抑郁症的发病有关,但其确切机制仍不清楚。抑郁症的发病是环境和遗传因素共同作用的结果。DNA 甲基化是一种重要的表观遗传修饰,在创伤后应激障碍(PTSD)、抑郁症和自闭症等精神疾病的发病机制中起着调节作用。在我们的研究中,我们观察到与对照组小鼠相比,LPS诱导的抑郁症小鼠海马DG区的Dnmt3a表达水平降低。抗抑郁药文拉法辛能够提高 Dnmt3a 的表达水平。相反,L 型 Ca2+ 通道激动剂 Bay K 8644 可部分改善抑郁样行为,但不会提高 Dnmt3a 的表达水平。此外,当我们在对抑郁样模型进行 BAY K 8644 干预时操纵 DNA 甲基化水平,我们发现提高 Dnmt3a 的表达可以改善 LPS 诱导的抑郁/焦虑样行为,而抑制 DNA 甲基化则会加剧焦虑样行为,联合使用 BAY K 8644 和 L-蛋氨酸可以更好地改善抑郁样行为。这些研究结果表明,DNA甲基化在L型Ca2+通道对抑郁样行为的调控中起着一定的作用,而DNA甲基化与L型Ca2+通道之间的相互作用还需要进一步的研究来阐明。
{"title":"L-methionine and the L-type Ca2+ channel agonist BAY K 8644 collaboratively contribute to the reduction of depressive-like behavior in mice","authors":"Ershu He, Ruixue Ma, Shanglan Qu, Xiaoye Zheng, Xin Peng, Jieyu Ji, Wenhao Ma, Xueyan Zhang, Ying Li, Hanwei Li, Yanjiao Li, Lijuan Li, Zhiting Gong","doi":"10.3389/fncir.2024.1435507","DOIUrl":"https://doi.org/10.3389/fncir.2024.1435507","url":null,"abstract":"The L-type Ca<jats:sup>2+</jats:sup> channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca<jats:sup>2+</jats:sup> channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca<jats:sup>2+</jats:sup> channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca<jats:sup>2+</jats:sup> channels.","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"68 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Frontiers in Neural Circuits
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1