Alicia N Vagnozzi, Matthew T Moore, Raquel López de Boer, Aambar Agarwal, Niccolò Zampieri, Lynn T Landmesser, Polyxeni Philippidou
{"title":"Catenin signaling controls phrenic motor neuron development and function during a narrow temporal window.","authors":"Alicia N Vagnozzi, Matthew T Moore, Raquel López de Boer, Aambar Agarwal, Niccolò Zampieri, Lynn T Landmesser, Polyxeni Philippidou","doi":"10.3389/fncir.2023.1121049","DOIUrl":"10.3389/fncir.2023.1121049","url":null,"abstract":"<p><p>Phrenic Motor Column (PMC) neurons are a specialized subset of motor neurons (MNs) that provide the only motor innervation to the diaphragm muscle and are therefore essential for survival. Despite their critical role, the mechanisms that control phrenic MN development and function are not well understood. Here, we show that catenin-mediated cadherin adhesive function is required for multiple aspects of phrenic MN development. Deletion of β- and γ-<i>catenin</i> from MN progenitors results in perinatal lethality and a severe reduction in phrenic MN bursting activity. In the absence of catenin signaling, phrenic MN topography is eroded, MN clustering is lost and phrenic axons and dendrites fail to grow appropriately. Despite the essential requirement for catenins in early phrenic MN development, they appear to be dispensable for phrenic MN maintenance, as catenin deletion from postmitotic MNs does not impact phrenic MN topography or function. Our data reveal a fundamental role for catenins in PMC development and suggest that distinct mechanisms are likely to control PMC maintenance.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1121049"},"PeriodicalIF":3.5,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9705852","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":"Effect of galvanic vestibular stimulation applied at the onset of stance on muscular activity and gait cycle duration in healthy individuals.","authors":"Faezeh Abbariki, Youstina Mikhail, Adjia Hamadjida, Jonathan Charron, Jean-Marc Mac-Thiong, Dorothy Barthélemy","doi":"10.3389/fncir.2022.1065647","DOIUrl":"10.3389/fncir.2022.1065647","url":null,"abstract":"<p><p>Locomotion requires the complex involvement of the spinal and supraspinal systems. So far, the role of vestibular input in gait has been assessed mainly with respect to gait stability. The noninvasive technique of galvanic vestibular stimulation (GVS) has been reported to decrease gait variability and increase gait speed, but the extent of its effect on spatiotemporal gait parameters is not fully known. <b>Objective:</b> Characterize vestibular responses during gait and determine the influence of GVS on cycle duration in healthy young participants. <b>Methods:</b> Fifteen right-handed individuals participated in the study. Electromyography (EMG) recordings of the bilateral soleus (SOL) and tibialis anterior muscles (TA) were performed. First, to determine stimulation intensity, an accelerometer placed on the vertex recorded the amplitude of the head tilts evoked by the GVS (1-4 mA, 200 ms) to establish a motor threshold (T). Second, while participants walked on a treadmill, GVS was applied at the onset of the stance phase during the treadmill gait with an intensity of 1 and 1.5 T with the cathode behind the right (RCathode) or left ear (LCathode). EMG traces were rectified, averaged (<i>n</i> = 30 stimuli), and analyzed. Latency, duration, and amplitude of vestibular responses as well as the mean duration of the gait cycles were measured. <b>Results:</b> GVS mainly induced long-latency responses in the right SOL, right TA and left TA. Only short-latency responses were triggered in the left SOL. Responses in the right SOL, left SOL and left TA were polarity dependent, being facilitatory with RCathode and inhibitory with LCathode, whereas responses in the right TA remained facilitatory regardless of the polarity. With the RCathode configuration, the stimulated cycle was prolonged compared with the control cycle at both 1 and 1.5 T, due to prolonged left SOL and TA EMG bursts, but no change was observed in right SOL and TA. With LCathode, GVS did not modify the cycle duration. <b>Conclusion:</b> During gait, a brief, low-intensity GVS pulse delivered at the right stance onset induced mainly long-latency polarity-dependent responses. Furthermore, a RCathode configuration increased the duration of the stimulated gait cycle by prolonging EMG activity on the anodic side. A similar approach could be explored to influence gait symmetry in individuals with neurological impairment.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"16 ","pages":"1065647"},"PeriodicalIF":3.5,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356978","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}
Zhenyang Sun, David Crompton, Milad Lankarany, Frances K Skinner
{"title":"Reduced oriens-lacunosum/moleculare cell model identifies biophysical current balances for <i>in vivo</i> theta frequency spiking resonance.","authors":"Zhenyang Sun, David Crompton, Milad Lankarany, Frances K Skinner","doi":"10.3389/fncir.2023.1076761","DOIUrl":"10.3389/fncir.2023.1076761","url":null,"abstract":"<p><p>Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful \"tools\" that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With advances in cell imaging and computational power, multi-compartment models with morphological accuracy are becoming common practice. However, as more biological details are added, they make extensive explorations and analyses more challenging largely due to their huge computational expense. Here, we focus on oriens-lacunosum/moleculare (OLM) cell models. OLM cells can contribute to functionally relevant theta rhythms in the hippocampus by virtue of their ability to express spiking resonance at theta frequencies, but what characteristics underlie this is far from clear. We converted a previously developed detailed multi-compartment OLM cell model into a reduced single compartment model that retained biophysical fidelity with its underlying ion currents. We showed that the reduced OLM cell model can capture complex output that includes spiking resonance in <i>in vivo</i>-like scenarios as previously obtained with the multi-compartment model. Using the reduced model, we were able to greatly expand our <i>in vivo</i>-like scenarios. Applying spike-triggered average analyses, we were able to to determine that it is a combination of hyperpolarization-activated cation and muscarinic type potassium currents that specifically allow OLM cells to exhibit spiking resonance at theta frequencies. Further, we developed a robust Kalman Filtering (KF) method to estimate parameters of the reduced model in real-time. We showed that it may be possible to directly estimate conductance parameters from experiments since this KF method can reliably extract parameter values from model voltage recordings. Overall, our work showcases how the contribution of cellular biophysical current details could be determined and assessed for spiking resonance. As well, our work shows that it may be possible to directly extract these parameters from current clamp voltage recordings.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1076761"},"PeriodicalIF":3.4,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10828165","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":"Ventral pallidal regulation of motivated behaviors and reinforcement.","authors":"Carina Soares-Cunha, Jasper A Heinsbroek","doi":"10.3389/fncir.2023.1086053","DOIUrl":"10.3389/fncir.2023.1086053","url":null,"abstract":"<p><p>The interconnected nuclei of the ventral basal ganglia have long been identified as key regulators of motivated behavior, and dysfunction of this circuit is strongly implicated in mood and substance use disorders. The ventral pallidum (VP) is a central node of the ventral basal ganglia, and recent studies have revealed complex VP cellular heterogeneity and cell- and circuit-specific regulation of reward, aversion, motivation, and drug-seeking behaviors. Although the VP is canonically considered a relay and output structure for this circuit, emerging data indicate that the VP is a central hub in an extensive network for reward processing and the regulation of motivation that extends beyond classically defined basal ganglia borders. VP neurons respond temporally faster and show more advanced reward coding and prediction error processing than neurons in the upstream nucleus accumbens, and regulate the activity of the ventral mesencephalon dopamine system. This review will summarize recent findings in the literature and provide an update on the complex cellular heterogeneity and cell- and circuit-specific regulation of motivated behaviors and reinforcement by the VP with a specific focus on mood and substance use disorders. In addition, we will discuss mechanisms by which stress and drug exposure alter the functioning of the VP and produce susceptibility to neuropsychiatric disorders. Lastly, we will outline unanswered questions and identify future directions for studies necessary to further clarify the central role of VP neurons in the regulation of motivated behaviors. <b>Significance:</b> Research in the last decade has revealed a complex cell- and circuit-specific role for the VP in reward processing and the regulation of motivated behaviors. Novel insights obtained using cell- and circuit-specific interrogation strategies have led to a major shift in our understanding of this region. Here, we provide a comprehensive review of the VP in which we integrate novel findings with the existing literature and highlight the emerging role of the VP as a linchpin of the neural systems that regulate motivation, reward, and aversion. In addition, we discuss the dysfunction of the VP in animal models of neuropsychiatric disorders.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1086053"},"PeriodicalIF":3.4,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10819262","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":"Editorial: The neural circuitry of mating behaviors.","authors":"Stefano Zucca, Adam C Puche, Serena Bovetti","doi":"10.3389/fncir.2022.1102051","DOIUrl":"10.3389/fncir.2022.1102051","url":null,"abstract":"","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"16 ","pages":"1102051"},"PeriodicalIF":3.5,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579520","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":"Minocycline prevents hypoxia-induced seizures.","authors":"Isato Fukushi, Keiko Ikeda, Kotaro Takeda, Masashi Yoshizawa, Yosuke Kono, Yohei Hasebe, Mieczyslaw Pokorski, Yasumasa Okada","doi":"10.3389/fncir.2023.1006424","DOIUrl":"https://doi.org/10.3389/fncir.2023.1006424","url":null,"abstract":"<p><p>Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O<sub>2</sub> in N<sub>2</sub>) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1006424"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10073501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9272835","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}
Camila Chacon, Chioma V Nwachukwu, Narjes Shahsavani, Kristine C Cowley, Jeremy W Chopek
{"title":"Lumbar V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons, linking locomotor, and autonomic spinal systems.","authors":"Camila Chacon, Chioma V Nwachukwu, Narjes Shahsavani, Kristine C Cowley, Jeremy W Chopek","doi":"10.3389/fncir.2023.1235181","DOIUrl":"https://doi.org/10.3389/fncir.2023.1235181","url":null,"abstract":"<p><p>Although sympathetic autonomic systems are activated in parallel with locomotion, the neural mechanisms mediating this coordination are incompletely understood. Sympathetic preganglionic neurons (SPNs), primarily located in the intermediate laminae of thoracic and upper lumbar segments (T1-L2), increase activation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. Recent evidence suggests integration between locomotor and autonomic nuclei occurs within the brainstem, initiating both descending locomotor and sympathetic activation commands. However, both locomotor and sympathetic autonomic spinal systems can be activated independent of supraspinal input, in part due to a distributed network involving propriospinal neurons. Whether an intraspinal mechanism exists to coordinate activation of these systems is unknown. We hypothesized that ascending spinal neurons located in the lumbar region provide synaptic input to thoracic SPNs. Here, we demonstrate that synaptic contacts from locomotor-related V3 interneurons (INs) are present in all thoracic laminae. Injection of an anterograde tracer into lumbar segments demonstrated that 8-20% of glutamatergic input onto SPNs originated from lumbar V3 INs and displayed a somatotopographical organization of synaptic input. Whole cell patch clamp recording in SPNs demonstrated prolonged depolarizations or action potentials in response to optical activation of either lumbar V3 INs in spinal cord preparations or in response to optical activation of V3 terminals in thoracic slice preparations. This work demonstrates a direct intraspinal connection between lumbar locomotor and thoracic sympathetic networks and suggests communication between motor and autonomic systems may be a general function of the spinal cord.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1235181"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10244475","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}
Akil Khalid, Pragnya P Prusty, Iqra Arshad, Hannah E Gustafson, Isra Jalaly, Keith Nockels, Barry L Bentley, Rahul Goel, Elisa R Ferrè
{"title":"Pharmacological and non-pharmacological countermeasures to Space Motion Sickness: a systematic review.","authors":"Akil Khalid, Pragnya P Prusty, Iqra Arshad, Hannah E Gustafson, Isra Jalaly, Keith Nockels, Barry L Bentley, Rahul Goel, Elisa R Ferrè","doi":"10.3389/fncir.2023.1150233","DOIUrl":"https://doi.org/10.3389/fncir.2023.1150233","url":null,"abstract":"<p><strong>Introduction: </strong>Space Motion Sickness (SMS) is a syndrome that affects around 70% of astronauts and includes symptoms of nausea, dizziness, fatigue, vertigo, headaches, vomiting, and cold sweating. Consequences range from discomfort to severe sensorimotor and cognitive incapacitation, which might cause potential problems for mission-critical tasks and astronauts and cosmonauts' well-being. Both pharmacological and non-pharmacological countermeasures have been proposed to mitigate SMS. However, their effectiveness has not been systematically evaluated. Here we present the first systematic review of published peer-reviewed research on the effectiveness of pharmacological and non-pharmacological countermeasures to SMS.</p><p><strong>Methods: </strong>We performed a double-blind title and abstract screening using the online Rayyan collaboration tool for systematic reviews, followed by a full-text screening. Eventually, only 23 peer-reviewed studies underwent data extraction.</p><p><strong>Results: </strong>Both pharmacological and non-pharmacological countermeasures can help mitigate SMS symptoms.</p><p><strong>Discussion: </strong>No definitive recommendation can be given regarding the superiority of any particular countermeasure approach. Importantly, there is considerable heterogeneity in the published research methods, lack of a standardized assessment approach, and small sample sizes. To allow for consistent comparisons between SMS countermeasures in the future, standardized testing protocols for spaceflight and ground-based analogs are needed. We believe that the data should be made openly available, given the uniqueness of the environment in which it is collected.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021244131.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1150233"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9948985","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":"Spinal inhibitory interneurons: regulators of coordination during locomotor activity.","authors":"Simon Gosgnach","doi":"10.3389/fncir.2023.1167836","DOIUrl":"https://doi.org/10.3389/fncir.2023.1167836","url":null,"abstract":"<p><p>Since the early 1900's it has been known that a neural network, situated entirely within the spinal cord, is capable of generating the movements required for coordinated locomotion in limbed vertebrates. Due the number of interneurons in the spinal cord, and the extent to which neurons with the same function are intermingled with others that have divergent functions, the components of this neural circuit (now referred to as the locomotor central pattern generator-CPG) have long proven to be difficult to identify. Over the past 20 years a molecular approach has been incorporated to study the locomotor CPG. This approach has resulted in new information regarding the identity of its component interneurons, and their specific role during locomotor activity. In this mini review the role of the inhibitory interneuronal populations that have been shown to be involved in locomotor activity are described, and their specific role in securing left-right, and flexor extensor alternation is outlined. Understanding how these interneuronal populations are activated, modulated, and interact with one another will help us understand how locomotor behavior is produced. In addition, a deeper understanding of the structure and mechanism of function of the locomotor CPG has the potential to assist those developing strategies aimed at enhancing recovery of motor function in spinal cord injured patients.</p>","PeriodicalId":12498,"journal":{"name":"Frontiers in Neural Circuits","volume":"17 ","pages":"1167836"},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805644","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}