{"title":"The neuronal Golgi in neural circuit formation and reorganization.","authors":"Naoki Nakagawa","doi":"10.3389/fncir.2024.1504422","DOIUrl":"https://doi.org/10.3389/fncir.2024.1504422","url":null,"abstract":"<p><p>The Golgi apparatus is a central hub in the intracellular secretory pathway. By positioning in the specific intracellular region and transporting materials to spatially restricted compartments, the Golgi apparatus contributes to the cell polarity establishment and morphological specification in diverse cell types. In neurons, the Golgi apparatus mediates several essential steps of initial neural circuit formation during early brain development, such as axon-dendrite polarization, neuronal migration, primary dendrite specification, and dendritic arbor elaboration. Moreover, neuronal activity-dependent remodeling of the Golgi structure enables morphological changes in neurons, which provides the cellular basis of circuit reorganization during postnatal critical period. In this review, I summarize recent findings illustrating the unique Golgi positioning and its developmental dynamics in various types of neurons. I also discuss the upstream regulators for the Golgi positioning in neurons, and functional roles of the Golgi in neural circuit formation and reorganization. Elucidating how Golgi apparatus sculpts neuronal connectivity would deepen our understanding of the cellular/molecular basis of neural circuit development and plasticity.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"18 ","pages":"1504422"},"PeriodicalIF":3.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863065","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}
Natalie Lipari, Ashley Galfano, Shruti Venkatesh, Han Grezenko, Ivette M Sandoval, Fredric P Manfredsson, Christopher Bishop
{"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}
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}
{"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}
{"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}
{"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}
Irakli Intskirveli, Susan Gil, Ronit Lazar, Raju Metherate
{"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}
Andrei Rozov, David John Jappy, Ksenia Maltseva, Alina Vazetdinova, Fliza Valiullina-Rakhmatullina
{"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}
{"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}
Mohammad Yaghoubi, Javier G. Orlandi, Michael A. Colicos, Jörn Davidsen
{"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}