Elora K Reilly, Aleeza Kadri, Joseph W Arthurs, Jonathan R Sedano, Allison N Brezinski, Nathan A Baertsch
{"title":"A projection atlas of excitatory and inhibitory inputs to the preBötzinger complex: substrates for multimodal breathing control.","authors":"Elora K Reilly, Aleeza Kadri, Joseph W Arthurs, Jonathan R Sedano, Allison N Brezinski, Nathan A Baertsch","doi":"10.1152/jn.00148.2026","DOIUrl":"10.1152/jn.00148.2026","url":null,"abstract":"<p><p>Breathing is an essential motor behavior that originates from the activity of rhythm-generating neurons in the preBötzinger complex (preBötC). Although the properties of preBötC neurons are sufficient for rhythmogenesis, their activity is continually shaped by long-range inputs that convey homeostatic, emotional, volitional, and behavioral influences. Here, we provide a systematic survey of projections from excitatory (glutamatergic) and inhibitory (GABAergic) neurons across the mouse brain that target the preBötC. Using a dual recombinase-dependent retrograde tracing approach, we compile an atlas of afferent regions, highlighting the breadth of excitatory and inhibitory inputs that converge on this critical brainstem area. This atlas underscores the preBötC as a nexus where multimodal signals are integrated to regulate rhythm generation and patterning. Rather than a self-contained oscillator, the preBötC is a hub whose function is tuned by diverse long-range excitatory and inhibitory influences. By defining the anatomical substrates of this input, we lay a foundation for dissecting the functional roles of higher-order brain regions in shaping breathing across physiological, behavioral, and pathological contexts.<b>NEW & NOTEWORTHY</b> The rhythm for each breath is generated by a specialized brainstem region called the preBötzinger complex. Many brain areas influence this region, but the sources of these inputs-and whether they excite or inhibit breathing-have not been systematically mapped. Here, we present an atlas identifying where excitatory and inhibitory signals to the preBötzinger complex arise across the mouse brain, providing a framework for understanding how breathing is shaped by sensory signals, behavior, and brain state.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"782-806"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648776","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}
Charlotte L Barkan, Lucas A Binder, Brett A Davis, Lucia Carbone, Erik Zornik
{"title":"Transcriptomic profiling reveals neurophysiological gene candidates underlying vocal evolution in African clawed frogs.","authors":"Charlotte L Barkan, Lucas A Binder, Brett A Davis, Lucia Carbone, Erik Zornik","doi":"10.1152/jn.00037.2026","DOIUrl":"10.1152/jn.00037.2026","url":null,"abstract":"<p><p>Neurophysiologists have discovered many mechanisms underlying the production of animal behaviors in specific species; these involve a collection of neuromuscular systems, neuronal membrane and neural network properties, as well as the hormones and neuromodulators known to modify them. However, the mechanistic basis of behavioral evolution is less well studied, and causal links between differences in gene expression, cellular mechanisms, and species-typical behaviors are rare. Vertebrate vocal behaviors are an excellent system for studying the evolution of behaviors because they are ancient, diverse, and readily quantifiable. <i>Xenopus</i> frogs are particularly well suited to the study of vocal evolution because of the temporal diversity of male advertisement calls between closely related species and the well-described vocal pattern-generating circuitry. Here we focus on two species, <i>X. laevis</i> and <i>X. petersii</i>, that diverged 8.5 million years ago and produce advertisement calls with distinct timing. To begin bridging the gap between behavioral and mechanistic diversity in <i>Xenopus</i> vocal behaviors, we performed RNA sequencing of the parabrachial nucleus, a vocal premotor hindbrain area known to encode species-typical temporal patterns in <i>X. laevis</i> and <i>X. petersii</i>. We identified hundreds of differentially expressed genes between the two species, including many genes related to hormone signaling, neuromodulation, neuronal and synaptic functions, ion channels, and neurotransmitter receptors. We explore several testable hypotheses emerging from these results that may explain mechanisms by which candidate genes and gene families contribute to vocal pattern differences between <i>X. laevis</i> and <i>X. petersii</i>.<b>NEW & NOTEWORTHY</b> This study is the first attempt in <i>Xenopus</i> frogs to link gene expression to circuit function to behavior in order to understand the neuronal mechanisms underlying vocal evolution.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"689-701"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549572","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}
Saleh Altahini, Ting Fu, Hendrik Backhaus, Afsaneh Labbaf, Marta Méndez-Couz, Albrecht Stroh
{"title":"Is 3 really better than 2? In vivo functional calcium imaging of cortical circuits by two- and three-photon microscopy.","authors":"Saleh Altahini, Ting Fu, Hendrik Backhaus, Afsaneh Labbaf, Marta Méndez-Couz, Albrecht Stroh","doi":"10.1152/jn.00502.2025","DOIUrl":"10.1152/jn.00502.2025","url":null,"abstract":"<p><p>Functional calcium imaging with genetically encoded calcium indicators (GECIs) has become a cornerstone of preclinical in vivo circuit analysis. Yet, due to light scattering, two-photon (2P) functional calcium imaging has been largely confined to superficial cortical layers in rodent models. Three-photon (3P) excitation offers deeper penetration due to reduced scattering of longer excitation wavelengths, but lower repetition rates of 3P laser systems impose a significant limitation on temporal resolution. Therefore, 3P calcium imaging of cortical microcircuits is still in its infancy. In this study, we performed a back-to-back comparison of 2P and 3P functional calcium imaging in the visual cortex of awake, head-fixed mice. We assessed the efficacy of 3P imaging to capture the local functional microcircuit dynamics in the visual cortex. 3P imaging not only revealed neuronal somata and neuropil in layers V/VI with robust morphological SNR but also generated label-free contrast of the blood vessels via third harmonic generation. Functionally, in superficial layers, a comparable functional architecture was assessed with both methods; while 3P detected lower firing frequencies, the underlying circuit dynamics, such as functional connectivity, remained consistent with 2P recordings. Notably in layers V/VI, while 2P failed to resolve the functional circuit state, with 3P a functional readout of neuronal circuits became achievable. These results demonstrate that, despite its current temporal limitations, 3P calcium imaging can reliably capture the functional architecture across all cortical layers, providing unmatched depth penetration and vascular contrast.<b>NEW & NOTEWORTHY</b> This study explores the capability of three-photon functional imaging to resolve functional cortical architecture in mice. By a quantitative, back-to-back comparison in awake head-fixed mice, we demonstrate that three-photon imaging is equally capable compared to two-photon imaging at superficial layers (II/III) and allows functional assessment of deep cortical layers (V/VI), beyond the reach of conventional two-photon microscopy.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"653-663"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520399","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}
James MacLeod, Bella Xu-Ying, Maarten F Zwart, Stefan R Pulver
{"title":"Dopamine promotes motor programs underlying substrate tunneling in larval <i>Drosophila</i>.","authors":"James MacLeod, Bella Xu-Ying, Maarten F Zwart, Stefan R Pulver","doi":"10.1152/jn.00469.2025","DOIUrl":"10.1152/jn.00469.2025","url":null,"abstract":"<p><p>Dopamine is a conserved biogenic amine with diverse neuromodulatory roles. Here we examine the role of dopamine in modulating larval <i>Drosophila melanogaster</i> motor programs underlying movement over and through substrates. First, we performed dual-color calcium imaging in tyrosine hydroxylase (TH)-expressing dopaminergic neurons and motor neurons to reveal cell-type-specific recruitment patterns during fictive motor programs. Activity of select TH neurons correlated strongly with fictive headsweeps as well as forward and backward locomotion. Next, bath applications of dopamine biased the isolated central nervous system toward fictive forward locomotion and inhibited fictive headsweeps. To probe whether these effects are recapitulated in intact animals, we optogenetically manipulated TH neuron activity during surface crawling and tunneling. Optogenetic activation of TH neurons with CsChrimson during crawling had no effect on headsweeps and slowed locomotor rhythms by increasing wave duration and decreasing wave frequency. Furthermore, posterior asymmetries, motor sequences characteristic of tunneling, were triggered. On the other hand, optogenetically inhibiting TH neurons with GtACR1 had little effect on surface crawling. Underground, TH-neuron activation enhanced tunneling activity by increasing wave frequency, instead of duration, which increased overall time spent tunneling, whereas inhibition decreased time spent tunneling. These results suggest that dopaminergic modulation of larval forward locomotion is dependent on sensorimotor context. We propose dopamine mediates a coordinated network effort to shift central pattern generators to promote tunneling-specific motor programs.<b>NEW & NOTEWORTHY</b> Here, we find <i>Drosophila</i> larval dopaminergic neurons exhibit cell-type-specific activity in relation to fictive motor patterns. Furthermore, pharmacological and optogenetic manipulations of dopaminergic signaling acutely modify locomotor output. Specifically, dopamine application promotes forward locomotion and inhibits headsweeps in isolated preparations, while optogenetically activating tyrosine hydroxylase neurons in freely behaving larvae mediates a shift from crawling to tunneling motor programs. This provides new insights into context-dependent dopaminergic modulation of locomotion in a genetically tractable invertebrate.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"824-836"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648756","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}
Shuping Jia, Nataliya Rybalchenko, Obed T Paundralingga, Cephas B Appiah, George E Farmer, J Thomas Cunningham
{"title":"Chronic intermittent hypoxia increases EPSC frequency in median preoptic nucleus neurons through BDNF-TrkB signaling in a sex-dependent manner.","authors":"Shuping Jia, Nataliya Rybalchenko, Obed T Paundralingga, Cephas B Appiah, George E Farmer, J Thomas Cunningham","doi":"10.1152/jn.00265.2026","DOIUrl":"10.1152/jn.00265.2026","url":null,"abstract":"<p><p>Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea, produces a sustained sympathetically mediated increase in blood pressure. The median preoptic nucleus (MnPO) contributes to CIH-induced sympathoexcitation via projections to the paraventricular nucleus of the hypothalamus (PVN). However, the synaptic mechanisms underlying CIH-induced increased activity in this pathway remain to be determined. In addition, the impact of sex on MnPO synaptic changes in CIH exposure is unknown. We hypothesized that CIH affects MnPO synaptic activity differently between sexes and that brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling plays a role in CIH-mediated changes in the MnPO-PVN pathway. We performed whole cell voltage-clamp recordings from MnPO neurons in brain slices from male and female rats exposed to either normoxia or 7 days of CIH. In PVN-projecting MnPO neurons, CIH increased mEPSC frequency only in males, while females showed a reduction in mEPSC amplitude to CIH. CIH also increased BDNF expression in the MnPO of males exposed to CIH but not in females. Pharmacological studies in male rats using K252a, K252b, and ANA-12 attenuated the CIH-induced increase in mEPSC frequency, indicating that BDNF-TrkB signaling is essential for CIH. These findings highlight a sex-specific, TrkB-dependent mechanism that enhances excitatory signaling between the MnPO and PVN. In conclusion, our study shows that PVN-projecting MnPO neurons demonstrate sex-based changes in mEPSCs and that BDNF-TrkB signaling contributes to the CIH-induced increase in mEPSC frequency in neurons from males.<b>NEW & NOTEWORTHY</b> Chronic intermittent hypoxia (CIH) mimics arterial hypoxemia associated with sleep apnea. These studies demonstrate that CIH produces sex-dependent changes in mEPSC properties in paraventricular nucleus (PVN) projecting median preoptic nucleus (MnPO) neurons. In neurons from male rats, BDNF contributes to CIH-induced changes in mEPSC frequency. As the PVN directly innervates the sympathetic system, this could be a possible mechanism contributing to sustained sympathoexcitation in CIH.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"772-781"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648835","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":"Separate dorsolateral prefrontal cortex regions participate in distinct large-scale networks differentially recruited for social and cognitive control functions.","authors":"Lauren M DiNicola, Randy L Buckner","doi":"10.1152/jn.00099.2026","DOIUrl":"10.1152/jn.00099.2026","url":null,"abstract":"<p><p>Human prefrontal cortex (PFC) is heterogeneous. In monkeys, side-by-side PFC regions, including within dorsolateral PFC (DLPFC), show distinct long-range anatomical projection profiles, raising the possibility that separate DLPFC regions might specialize as a consequence of the distributed networks in which they are embedded. Recent findings in humans provide evidence for PFC regions preferentially responding to scene (spatial) processing or language processing that are adjacent to distinct domain-flexible regions responding to traditional cognitive control demands. Here, we tested functional specialization of PFC regions linked to another domain-preferential network recruited by certain forms of social processing (theory-of-mind, ToM, tasks). Using within-individual precision neuroimaging approaches, two anatomically distinct DLPFC regions embedded within parallel distributed networks were identified within the idiosyncratic anatomy of each individual (<i>n</i> = 13). Functional responses between these distinct regions revealed a robust functional double dissociation: one DLPFC region was preferentially recruited by ToM tasks and a nearby DLPFC region by working memory task demands. The region responding to social processing demands was small and its position varied slightly from one person to the next, suggesting why it may have been underappreciated in past group-based analyses. These findings add to evidence that PFC features more functional specialization than commonly appreciated and further that the specialization of distinct regions within PFC can be understood by examining the distributed networks within which the regions are embedded.<b>NEW & NOTEWORTHY</b> Dorsolateral prefrontal cortex (DLPFC) is often heuristically associated with domain-flexible cognitive control, rather than specialization for social processing. Here, using precision neuroimaging, we identify a DLPFC region of a domain-preferential network linked to social inference. This region also shows preferential response to theory-of-mind tasks, distinct from nearby regions of a control-relevant network that respond flexibly to working memory task demands. Results add evidence that DLPFC features distinct domain-flexible and domain-specialized regions, with functions aligned to broader networks.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"634-642"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396872","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}
Nafiz Ishtiaque Ahmed, Tharan Suresh, Sara J Hussain, Michael Freedberg
{"title":"Incorporating motor preparation time transforms micro-offline gains into micro-offline losses.","authors":"Nafiz Ishtiaque Ahmed, Tharan Suresh, Sara J Hussain, Michael Freedberg","doi":"10.1152/jn.00181.2026","DOIUrl":"10.1152/jn.00181.2026","url":null,"abstract":"<p><p>During explicit sequence learning (ESL), micro-offline gains (MOGS) occur during brief rest periods. MOGS are calculated as the difference in sequence speed between the first correct sequence of one trial and the last sequence of the preceding trial. To date, all studies evaluating MOGS have calculated sequence speed from the execution time that occurs between keypresses, but this approach ignores potential contributions from motor preparation that occur before the first keypress. Given that ESL relies on both premovement motor planning and subsequent motor execution, we hypothesized that ignoring motor preparation time neglects a critical component of skill acquisition, potentially misrepresenting the true magnitude of MOGS. To test this, we calculated MOGS with and without preparation time in 30 adults who performed an ESL task. The dataset used for this analysis was obtained as part of a larger study to evaluate the effects of pretrial temporal predictability on ESL performance and learning by controlling the predictability of trial onset. Our results show that including preparation time flipped MOGS from positive to negative and significantly increased the positive correlation between early learning and a gold-standard ESL metric: the number of correct sequences performed. Our results suggest that preparation time should be incorporated into MOGS calculations and that excluding it overestimates micro-offline learning.<b>NEW & NOTEWORTHY</b> Current standards quantify micro-offline gains in terms of execution speed, entirely ignoring motor preparation time. If these gains reflect true learning, they should persist when accounting for premotor planning. Our results demonstrate a striking reversal: integrating motor preparation time completely flips micro-offline gains to micro-offline losses. Furthermore, by correcting this methodological artifact, our study provides a behaviorally validated, necessary framework for future studies investigating micro-offline gains.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"625-632"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471388","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}
Michail Arvanitidis, Patricio A Pincheira, Francesco Negro, Alberto Botter, Giacinto Luigi Cerone, Eduardo Martinez-Valdes
{"title":"Interactions between motor unit firing and fascicle dynamics during shortening and lengthening contractions.","authors":"Michail Arvanitidis, Patricio A Pincheira, Francesco Negro, Alberto Botter, Giacinto Luigi Cerone, Eduardo Martinez-Valdes","doi":"10.1152/jn.00188.2026","DOIUrl":"10.1152/jn.00188.2026","url":null,"abstract":"<p><p>The integration of high-density surface electromyography with ultrasound-transparent electrodes (HDsEMG-US) and B-mode ultrasonography enables concurrent assessment of motor unit (MU) firing properties and fascicle length (FL) from the same muscle region. Although the isometric relations between MU discharge, FL, and torque have been characterized, their interactions during anisometric contractions remain poorly understood. This study examined MU discharge behavior and its relation with FL changes during shortening and lengthening contractions of the tibialis anterior muscle. Ten healthy males performed isokinetic dorsiflexion contractions at a constant angular velocity of 2°/s while maintaining a constant submaximal torque of 25% maximum voluntary contraction torque, measured at a long muscle-tendon length (∼30° of plantarflexion), with HDsEMG-US signals and ultrasound images recorded simultaneously. MUs were identified using blind-source separation decomposition and FL was tracked with an optical flow algorithm. Cross-correlation analysis revealed high associations between cumulative spike train (CST), FL, and torque in both contraction phases. Neuromechanical delays were significantly longer during lengthening than shortening (phase effect: <i>F</i><sub>1,7</sub> = 8.51, <i>P</i> = 0.023; mean difference: -25.04 ms, 95% CI: -45.35 to -4.74). Discharge rate changed at a similar rate with variations in FL during both shortening and lengthening contractions (similar discharge rate-FL slopes, <i>P</i> = 0.44); however, absolute discharge rates were systematically lower during lengthening (difference in intercepts: <i>P</i> < 0.0001). These findings demonstrate the feasibility of HDsEMG-US for characterizing neuromechanical coupling during dynamic contractions and provide new evidence of neural drive regulation during shortening and lengthening muscle actions.<b>NEW & NOTEWORTHY</b> Using ultrasound-transparent high-density surface EMG, we simultaneously measured motor unit discharge and tibialis anterior fascicle length during shortening and lengthening contractions. Discharge rate was linearly related to fascicle length changes during both contraction types. However, when considering the same level of fascicle shortening between contractions, discharge rates were systematically lower during lengthening, and neuromechanical delays were prolonged, consistent with length-dependent adjustments in contractile properties. These findings provide new evidence of neuromechanical coupling during anisometric contractions.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"735-744"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549502","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}
Adara DeNiro, Shrinivasan Raghuraman, Kevin Chase, Baldomero M Olivera, Ayako Yamaguchi
{"title":"Molecular characterization of parabrachial neurons in <i>Xenopus laevis</i> and <i>Silurana tropicalis</i>: evolutionary conservation and sex-specific differences.","authors":"Adara DeNiro, Shrinivasan Raghuraman, Kevin Chase, Baldomero M Olivera, Ayako Yamaguchi","doi":"10.1152/jn.00058.2026","DOIUrl":"10.1152/jn.00058.2026","url":null,"abstract":"<p><p>Clawed frogs communicate acoustically to coordinate reproduction, with males producing species-specific advertisement calls to attract females. In <i>Xenopus laevis</i>, males generate fast trills composed of clicks repeated at 60 Hz, a feature absent in <i>Silurana tropicalis</i> males and <i>X. laevis</i> females, whose calls consist of slower click rates (30 Hz and 7 Hz, respectively). In male <i>X. laevis</i>, fast trills are generated by premotor neurons in the parabrachial nucleus (PBN), known as fast trill neurons (FTNs). We hypothesized that FTNs are unique in male <i>X. laevis</i> and absent or distinct in clawed frogs lacking fast trills. To test this, we used constellation pharmacology to profile receptor and ion channel expression in PBN neurons by measuring intracellular Ca<sup>2+</sup> responses to pharmacological agents in male <i>X. laevis</i>, male <i>S. tropicalis</i>, and female <i>X. laevis</i>. Surprisingly, we found putative FTNs (pFTNs) in all three groups. Furthermore, a similar proportion of pFTNs across groups expressed fast-kinetic voltage-gated potassium channels known to support rapid firing, indicating the presence of these channels does not correlate with producing fast trills. Instead, some of these channels were more prevalent in males of both species than in female <i>X. laevis</i>, suggesting a sex-specific, nonvocal function. These results suggest FTNs may have an unrecognized function conserved across species but were repurposed for fast trills during <i>X. laevis</i> speciation; alternatively, they may differ in unresolved molecular or electrophysiological properties, or represent latent ancestral circuitry persisting in slow-trilling species. These findings provide new insight into neural circuit evolution across species and sexes.<b>NEW & NOTEWORTHY</b> Premotor vocal neurons share molecular profiles across clawed frogs, despite differences in calls, revealing unexpected conservation and functional divergence of homologous neurons underlying the evolution of vocal behavior.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"709-721"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436889","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}
Caleb Stone, Jason B Mattingley, Nathan J Evans, Dragan Rangelov
{"title":"Cognitive training increases sensitivity to internal uncertainty during decision-making.","authors":"Caleb Stone, Jason B Mattingley, Nathan J Evans, Dragan Rangelov","doi":"10.1152/jn.00545.2025","DOIUrl":"10.1152/jn.00545.2025","url":null,"abstract":"<p><p>Metacognitive awareness of decision quality is important for adaptive decision-making. One marker of decision quality is the strength of internal evidence accumulation. Increasing sensitivity to evidence accumulation thus offers a potential mechanism for improving metacognition. To test this hypothesis, we trained two groups of participants (<i>n</i> = 34 per group) to reproduce the motion direction of one of two sequentially presented dot-motion stimuli. Participants in the forced-choice group were instructed which stimulus to respond to, whereas those in the free-choice group chose which stimulus they responded to. This manipulation targeted the instrumental value of metacognitive awareness, as participants in the free-choice group could use metacognition to optimize their choices. Before and after training, participants completed a near-transfer motion-discrimination task and provided metacognitive judgments, allowing us to assess how training altered sensitivity to evidence accumulation. Evidence accumulation was measured using the centroparietal positivity (CPP) and the drift rate. Participants in both groups performed better and exhibited improved metacognition following training. Training increased sensitivity to the predecisional CPP in the free-choice group and to the postdecisional CPP in the forced-choice group. Moreover, training increased sensitivity to the drift rate in the free-choice group but not the forced-choice group. These results provide novel insights into the neurocognitive mechanisms underlying training-induced improvements in metacognition.<b>NEW & NOTEWORTHY</b> We tested whether a novel training paradigm could increase participants' sensitivity to internal signals of decision quality and improve their decision-making and metacognition. Participants' behavioral performance improved following training, and this was accompanied by increased strength of the relationship between the centro-parietal positivity, a neural correlate of evidence accumulation, and participants' metacognitive judgments. Our work demonstrates that training can increase sensitivity to internal signals of decision uncertainty.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":" ","pages":"664-678"},"PeriodicalIF":2.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549533","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}