Developmental Neurobiology

The cerebellar nuclei form the main output structures of the cerebellum and are composed of a deeply conserved set of cell types. Two excitatory cell classes, Class-A and -B, are present in each cerebellar nucleus and mediate all excitatory output of the cerebellum. To provide genetic access to these cell types, here we identified Acan as a marker gene for Class-B cells and generated a knock-in Acan-P2A-Cre mouse line. We demonstrate that this Acan-Cre line selectively labels Class-B neurons in the cerebellar nuclei and validate its use in viral projection tracing. This new mouse line provides a valuable genetic tool to study cerebellar nuclei organization and function.

In contrast to many other developing systems, in which axon pathfinding and synaptogenesis are separated in time, the pioneering axon of the individually identifiable caudal primary motor neuron in embryonic zebrafish forms en passant synapses during its stereotypical ventral growth. How simultaneous synaptic differentiation and axon pathfinding are coordinated is not fully understood. Here we ask what the role of the tac1 gene, coding for the synaptic tachykinin neuropeptides, is in this unique axon differentiation process. The gene is expressed during axon outgrowth and its disruption results in increased branch length of CaP axons and subtle morphological defects of the pre-synapse. These abnormalities are accompanied by a robust [~]1.5-fold increase in motor neuron activity and in spontaneous early contractions in tac1-deficient embryos. Furthermore, pharmacological inhibition of the tachykinin receptor (Tacr1) leads to altered CaP axonal morphology, mimicking the axonal phenotype observed in tac1-deficient zebrafish. These findings suggest that tachykinin neuropeptides modulate formation and activity of en passant synapses and prevent aberrant axon branching during growth of zebrafish motor axons. HIGHLIGHTS- tac1 refines CaP primary motor axon development in zebrafish - Loss of tac1 disrupts presynaptic maturation at the horizontal myoseptum - tac1 mutants show elevated motor neuron activity and spontaneous contractions

The brain is one of the most complex animal organs but the development of the many different neuron types remains enigmatic. A set of brain-specific transcription factors is known to be involved in brain patterning but their specific contributions remain to be elucidated in most cases, including foxQ2II. This transcription factor is known to be conserved in anterior neuroectodermal patterning of most animals while it has been lost from vertebrates. However, the contribution of foxQ2II-positive neurons to the adult brain has remained enigmatic. Here, we use an enhancer trap, immunostainings and our newly established beetle brainbow system to categorize Tc-foxQ2II-positive neurons into nine clusters with different projection patterns. All clusters contain neurons with the fast activating neurotransmitters acetylcholine and glutamate while no Tc-foxQ2II positive neuron is GABA-ergic or serotonin-positive. Interestingly, we found that many dopaminergic neurons were Tc-foxQ2II positive and we homologize them with dopaminergic neurons of the PPL2c, PPM1 and PPL1 cluster described in the Drosophila brain. Our results show that Tc-foxQ2II marks subsets of fast-acting interneurons contributing to the higher order brain centers mushroom bodies and central complex. Taken together, our work expands the known functional range of foxQ2 genes from sensory and neurosecretory cell specification to interneurons involved in the function of higher order brain centers.

Developmental experience can produce lasting changes in neural function and behavior. Zebra finch offers a powerful model for identifying the molecular mechanisms underlying this process. Both juvenile male and female zebra finches perform developmental sensory song learning that influences their adult behaviors: in males, the structure of the song they sing and in female, the song preferences they exhibit (females cannot sing). The auditory forebrain, a region distinct from but connected to nodes of the male singing circuitry, is required for male sensory song learning. Song experience induces epigenetic, genomic, molecular, cellular and systems-level alterations in the auditory forebrain of males. Much less evidence is available for females. Although epigenetic and molecular data implicate the auditory forebrain in female sensory song learning, there has been no causal test of its role. Further, molecular evidence indicates the potential for distinct mechanisms for male and female sensory song learning, even though they learn during a largely overlapping developmental period. We used pharmacological manipulations of the ERK and mTOR cascades in the auditory forebrain of juvenile females during controlled tutoring, and an operant assay for adult song preference, to test the causal role of the auditory forebrain and the two cascades known to be required for male sensory song learning. We demonstrate that the auditory forebrain is required for female sensory song learning, and that while ERK signaling is necessary for both sexes, that of mTOR is sex specific. Results raise implications for alternative molecular cascade cross-talks and protein synthesis processes that successfully support the developmental learning at the same age and brain region.

Parental care can have pervasive effects on offsprings neurodevelopment. Parent-offspring interactions are often modulated by the neuropeptide oxytocin, which is responsible for the development of social bonds. The development of the oxytocinergic system is dependent on the quality of parental care during the post-natal phase. However, it is yet unknown how post-natal direct interactions can influence the development of the oxytocinergic pathway. Here we tested how an obligate parental care behaviour, tadpole transport in poison frogs, influences the development of the oxytocinergic pathway. To this end, we quantified whole brain expression of oxytocin receptor and oxytocin precursor throughout three developmental stages of A. femoralis tadpoles, before, during and after tadpole transport. Our results show an overall downregulation during tadpole transport, which indicates that during transport tadpoles enter a dormant state to slow down development until they are placed in water. Interestingly, the expression of oxytocin precursor did not vary between the three developmental stages. This might indicate that oxytocin is being recruited during transport, but does not lead to neurodevelopmental changes. In sum, here we present the first evidence of a dormant state during tadpole transport which might be an adaptive response to the terrestrial reproduction in poison frogs.

The mesencephalic trigeminal nucleus (MTN) contains the proprioceptive sensory neurons that innervate mechanoreceptors in the jaw closing muscles. In the chick embryo, MTN neurons are the first neurons generated in the mesencephalon. They arise bilaterally adjacent to the roof plate and then extend their axons ventrally before projecting caudally towards the rhombencephalon. MTN axons remain in a mid - dorsoventral position and pioneer the lateral longitudinal fasciculus. Notably, MTN axons never cross the roof plate, raising the question of which mechanisms underlie this restriction. Here, we investigated the effects of tissue transplants on the guidance of MTN axons. We found that both the diencephalon and the notochord exert repulsive effects on MTN axons, which could partially explain their early trajectory. We have also analysed the potential roles of the guidance cues BMP2/4, GDF7, SLIT and NETRIN in MTN axon navigation, both in vivo and in vitro. We found no evidence for a role of BMP2/4 or GDF7 in directing MTN axons. However, SLIT-ROBO signaling was found to play a significant role. SLIT proteins are repulsive guidance cues expressed by roof and floor plate. Loss or reduced expression of ROBO2 led to aberrant axon meandering within the dorsal midbrain. Most axons eventually reoriented posteriorly, and only a small fraction crossed the roof plate. Unexpectedly, in the absence of ROBO2, MTN somata migrated into the roof plate, resulting in the loss of a defined roof plate region. Taken together, these results suggest that SLIT2-ROBO2 signaling not only prevents MTN axons from crossing the roof plate but also maintains MTN cell bodies adjacent to the roof plate. With regards to MTN neuron guidance, we conclude that additional roof plate - derived factors are likely to co-operate with SLIT proteins to prevent crossing of the roof plate. Another possibility could be that SLIT might signal through additional receptors.

The transcription factor FOXP2 is the most well-known language-related gene in humans, yet its role in primate vocalization remains poorly understood. Here we report that knockdown of FOXP2 in the striatum markedly disrupts vocalization stability in the marmoset monkey, a valuable non-human primate model for studying vocal behavior. FOXP2 exhibited high expression in the marmoset striatum, especially during early development. Using the CRISPR-Cas12 system, we achieved specific in vivo editing of the FOXP2 gene and effective knockdown of FOXP2 protein expression in the marmoset striatum. Two neonatal marmosets received bilateral striatal injections of the gene-editing and control virus, respectively, and were raised together in the same family. In three such marmoset pairs, analysis of vocalizations recorded during 6-15 weeks post-injection revealed that striatal FOXP2 knockdown significantly altered vocal features and increased intra-individual variability in phee syllables--the most common marmoset vocalization, often produced repetitively as multi-syllable phee calls. Notably, in FOXP2-edited marmosets, acoustic alterations were minimal in the first syllable of phee calls but became progressively more pronounced in subsequent syllables, which exhibited a marked upward shift in the frequency spectrum over time with progressively steeper slopes. These temporal dynamics in vocal features reflect a reduction in the stability of continuous vocal production. In line with the known striatal functions in motor control, our findings provide the first evidence of FOXP2 in controlling vocalization in non-human primates, thereby opening new avenues for investigating the neural mechanisms underlying FOXP2 function.

Apathy is characterized by reduced motivation for goal-directed behaviour and may emerge following brain injury. Currently, little is known about apathy in children and adolescents with neurodevelopmental disorders (NDDs) exposed to repetitive head impacts. This exploratory study investigated associations between apathy, repetitive head-banging behaviour, and substantia nigra neuromelanin-sensitive MRI (NM-MRI) signal in youth with NDDs. Forty-seven participants (14 typically developing; 33 ADHD/ASD) completed Behaviour Assessment System for Children (BASC-3) measures, from which apathy-related items were harmonized across developmental forms and subjected to principal component analysis. A one-component solution explained 47.3% of variance and was used to derive apathy scores. Although head-banging severity and NM-MRI signal were not independently associated with apathy, a significant interaction emerged, whereby greater head-banging severity strengthened the relationship between apathy and substantia nigra NM-MRI signal. These preliminary findings suggest repetitive self-injurious head impacts may influence dopaminergic systems linked to motivational dysfunction in youth with NDDs.

IntroductionDown syndrome (DS), arising from Trisomy 21, is the most common genetic condition associated with intellectual disability. While smaller total brain volumes have been consistently observed in DS, no longitudinal neuroimaging studies have examined volumetric brain development in DS during infancy, a period of rapid neural growth when interventions may have the greatest impact. MethodHigh-resolution T1- and T2-weighted images were acquired during natural sleep in a multisite longitudinal cohort of 44 infants with DS and 39 control infants without DS at ages 6 and 12 months. Neuroimaging data were harmonized to reduce batch effects, and a novel deep-learning, repeated-measures segmentation approach was applied to optimize neuroanatomical segmentations. Total intracranial volume (ICV) and bilateral absolute subcortical volumes (amygdala, caudate, hippocampus, pallidum, putamen, thalamus) were first directly compared in infants with and without DS at 6 and 12 months. Hierarchical linear modeling (HLM) evaluated longitudinal group differences for each structure, accounting for sex, gestational age, and laterality. Subcortical group differences estimated by HLM were also compared to group differences in total ICV. ResultsICV in infants with DS was lower than controls at 6 months (12.6%; p<.001) and 12 months (16.3%; p<.001). Subcortical structures displayed a range of lower volumes (6.9%-13.1%; ps[&le;].003) in infants with DS, although the caudate and putamen were exceptions. Caudate volumes were on average lower in DS but not significantly different from controls, while putamen volumes were on average higher in DS but not significantly different from controls, except for the right putamen, which was significantly larger (5.3%; p=.018) at 6 months. In HLM, ICV and all subcortical structures showed slower growth in DS from 6 to 12 months, except for the amygdala and putamen, which displayed similar growth rates to controls. DS-associated reductions in subcortical volumes were similar in magnitude to ICV, although 12-month caudate and 6- and 12-month putamen volumes were enlarged relative to ICV. ConclusionInfants with DS exhibited substantially reduced ICV and widespread reductions in subcortical volumes and growth from 6-12 months. Across a range of volumetric differences, findings were most distinct in the basal ganglia, for which volume reductions were attenuated in the caudate, while the putamen was uniquely enlarged with comparable growth to controls. These observations support early regional specificity in the neural impact of Trisomy 21 and underscore the utility of infant neuroimaging to inform biologically based interventions and clinical trial readiness in DS.

Extensive experiments document that SPARCL1, a secreted protein that is produced primarily by astrocytes in brain and endothelia throughout the body and that is also known as Hevin, enhances synapse formation. However, the mode of action of SPARCL1 at synapses remains unclear owing to divergent results in the literature. Here, we use cultured neurons from newborn male and female mouse embryos to show that the C-terminal follistatin-like and Ca2+-binding domains of SPARCL1, which account for only 35% of the total SPARCL1 sequence, are sufficient to potently enhance synapse numbers. SPARCL1 acts at nanomolar concentrations at which SPARCL1 does not robustly bind to neurexins, neuroligins or neurexin/neuroligin complexes but avidly interacts with all teneurins. Strikingly, the follistatin-like domain of SPARCL1 on its own strongly binds to teneurins but is unable to stimulate synapse formation. Only when combined with the SPARCL1 Ca2+- binding domain does the follistatin-like domain induce synapses, suggesting that SPARCL1 enhances synapse numbers by binding to teneurins via its C-terminal follistatin-like domain and by activating synapse formation via its Ca2+-binding domain. SIGNIFICANCE STATEMENTSPARCL1 (also known as Hevin) is a synaptogenic factor that is produced primarily by astrocytes in brain, and that enhances synapse formation. How SPARCL1 acts at synapses, however, remains unclear because divergent results describe its binding partners at synapses and the sequences involved in its synaptogenic activity remain unclear. In the present study, we show that SPARCL1 avidly binds to the presynaptic teneurins adhesion molecules, that this binding is mediated by its small follistatin-like domain, and that its synaptogenic activity requires both its follistatin-like and its Ca2+-binding EC domains. Thus, our results suggest that SPARCL1 is recruited to developing synapses by binding of its follistatin-like domain to teneurins and then induces synapse assembly via its Ca2+-binding domain.

Hippocampal area CA2 has recently emerged as a critical region for social recognition memory. Furthermore, this understudied region has been implicated in psychiatric diseases and neurodegenerative diseases. There has been accumulating evidence indicating that the pyramidal neurons (PNs) in area CA2 exhibit functional specializations that correlate with somatic position in stratum pyramidale (sp). In this study, we investigated the morphological differences in dendritic architecture of CA2 PNs with a focus on the radial gradient, i.e., along the deep-superficial axis of the sp. We conducted a comprehensive morphological analysis including Sholl intersection profiles, branching order distributions, root angle distributions, and dendritic cable lengths. We found that CA2 PNs have fewer oblique dendrites and a larger number of tuft-like dendrites as compared to CA1 PNs. Furthermore, within the CA2 population, we found that many of the dendritic structural features gradually changed along the radial axis from deep to superficial somatic location, indicating a continuum of dendritic morphology rather than two sharply defined subtypes of pyramidal neurons. This morphological characterization may serve as a starting point to better understand the corresponding functional organization of CA2. The gradual difference between deeper and superficial CA2 PNs suggests a continuum of their computational capabilities beyond two binary functional classes. In briefUsing several methods, we examine the dendritic morphology of over 130 CA2 and CA1 pyramidal neurons and find that many properties such as the cable length and terminal numbers of the dendritic arbors vary as a with the location of the soma in the pyramidal layer. HighlightsO_LIWe use scholl analysis, graph theory and machine learning techniques to quantify the different dendritic morphologies of CA2 pyramidal neurons. C_LIO_LIMany properties of CA2 pyramidal neuron apical dendrites vary as a function of somatic location in the pyramidal layer. C_LIO_LIMore superficial CA2 pyramidal neurons have longer oblique apical dendrites, and shorter tuft dendrites. C_LI

Cav1.2 is an L-type voltage-gated Ca2+ channel (VGCC) that supports Ca2+ influx in response to membrane depolarization. Ca2+ entering via Cav1.2 alters gene expression, activates Ca2+-dependent enzymes and has been implicated in synaptic plasticity. ORL-1 is a Gi/o-coupled G protein-coupled receptor (GPCR) that is expressed in the peripheral and central nervous systems. Both Cav1.2 and ORL-1 are expressed in the hippocampus, where they have been implicated in learning and memory. It is well-documented that ORL-1 interacts with another VGCC, Cav2.2. However, less is known about potential interactions between Cav1.2 and ORL-1. Here, we examine the interplay between Cav1.2 (Cav1c, Cav2{delta}-1, Cav{beta}1) and ORL-1 co-expressed in tsA-201 cells by using biochemical, electrophysiological and confocal imaging analysis. Co-immunoprecipitations revealed that ORL-1 independently interacts with Cav1c and Cav2{delta}-1 subunits of the Cav1.2 channel complex. Electrophysiological recordings revealed that co-expression with ORL-1 reduced Cav1.2 peak current density without altering its biophysical properties. Acute perfusion with the ORL-1 receptor agonist nociceptin (1 M) did not alter Cav1.2 current density. Confocal imaging experiments revealed that ORL-1 significantly decreases Cav1.2 plasma membrane expression by disrupting forward trafficking. Interestingly, ORL-1 did not affect Cav1.2 endocytosis. Overall, our results demonstrate a previously unrecognized interaction between ORL-1 and Cav1.2 that alters Cav1.2 membrane expression without affecting biophysical properties.

Pigment epithelial-derived factor (PEDF) is a multifunctional protein produced predominantly by the retinal pigment epithelium and expressed in many tissues, including the brain, highlighting its participation in crucial processes, such as neuroprotection and angiogenesis. Some neurodevelopmental disorders, such as ASD, are characterized by neurodevelopmental abnormalities, including altered neurite formation, spine formation, and neuronal activities. Many efforts have been made to resolve NDDs, but until now, some symptoms remain untargeted. PEDF is involved in many steps of neurodevelopment. The treatment of PEDF peptide might improve the outcome of NDD symptoms by altering neuronal morphologies. We used PEDF peptides that contain different functional domains to study the effect of administering PEDF peptides on neuronal morphology in a prenatal valproic acid (VPA)-exposed mouse model. We identified that the treatment with PEDF peptides rectified the abnormalities in neurite formation and spine formation in VPA-exposed cortical neurons. In vitro calcium imaging showed abnormalities in the spontaneous activity in VPA-exposed cortical neurons. Treatment of a short PEDF peptide normalized intracellular calcium response to the control level. Accordingly, PEDF peptides have the prospect of serving as potential treatments for patients with neurodevelopmental disorders, such as ASD.

Neural progenitor cell differentiation is a complex process requiring the proper integration of instructive and permissive factors. Instructive cues including signaling molecules and transcription factor networks have been well studied in this context, but permissive factors such as cell homeostasis have not. Cell homeostasis is critical to support the health and stability of a cell and enable the cell to act on instructive differentiation cues. Our study investigates a homeostasis protein, FAF2, and its function in neural progenitor cells. FAF2 is an adaptor protein involved in endoplasmic reticulum (ER) associated degradation to remove misfolded proteins and restore ER homeostasis. Here we show that knocking out Faf2 in neural progenitor cells results in increased ER stress signature at the protein and transcription level, indicating a conserved functional role in neural progenitor cells. Induced neural differentiation of FAF2 deletion cells shows a failure of neurite development but RNA-seq indicates genes that support neural differentiation are induced. Reducing ER stress in FAF2 knockout cells with a small molecule inhibitor can rescue neural differentiation, providing evidence that excess ER stress contributes to the inhibited differentiation. Taken together, these results reveal that FAF2 is a critical protein in neural progenitor cells for the maintenance of ER homeostasis and execution of neural differentiation. Highlights- FAF2 is required to regulate ER homeostasis in neural progenitor cells - FAF2 knockout blocks differentiation of neural progenitor cells to neurons at the cell morphological level, but does not inhibit the mounting of transcriptional programs associated with neural differentiation. - Excess ER stress due to FAF2 knockout contributes to blocked neural differentiation.

Defining the direct postsynaptic targets of selected neuronal populations remains a major challenge for neural circuit mapping. Vesicular stomatitis virus (VSV) spreads efficiently in the anterograde direction, but replication-competent VSV undergoes multistep spread and therefore cannot distinguish direct from indirect downstream targets. Here, we developed a glycoprotein-deleted VSV (VSVdG)-based strategy for one-step anterograde tracing using AAV-mediated trans-complementation with several adaptations. In this system, VSVdG was engineered to encode Cre, allowing a Cre-dependent AAV to express VSV-G only after VSVdG infected the same cells, thereby limiting VSV-G expression to a short time window. To reduce VSV-M-mediated cytotoxicity, we introduced the M33A/M51R double-mutant VSV-Md variant. Using the basal ganglia circuit as a model, these adaptations enabled VSVdG spread from the striatum to expected downstream targets in mice of both sexes. Efficient VSVdG-based one-step spread required loss of type I interferon signaling in IFNAR1-knockout mice and additional suppression of cytokine-mediated antiviral responses that were independent of type I and type II interferon signaling. This was achieved either by AAV-mediated delivery of rabies virus phosphoprotein from the CVS-N2c strain or by a cytokine-blocking antibody cocktail. Although cells labeled by VSV transmission were confined to expected brain regions, the downstream labeled cells included both neurons and glia, revealing an important limitation for interpreting this approach as strictly neuron-to-neuron monosynaptic anterograde spread. Overall, this study provides a proof-of-concept VSVdG strategy for one-step anterograde circuit tracing and defines viral toxicity, innate immunity, and cell-type specificity constraints that must be addressed to develop a monosynaptic anterograde viral tracer. Significance StatementMapping direct downstream targets of defined neuronal populations is essential for understanding neural circuit function, but reliable monosynaptic anterograde viral tracers remain limited. We developed a VSVdG-based strategy that uses AAV-mediated trans-complementation to restrict VSV-G expression to starter cells in a short time window and incorporates a VSV-M variant to reduce toxicity. In the mouse basal ganglia, this system enabled one-step spread from the striatum to expected output regions when innate antiviral barriers were suppressed. Our results identify type I interferon and additional type I/type II interferon-independent cytokine signaling as major restrictions on VSVdG spread. This study establishes proof of principle for VSV-based one-step anterograde tracing while defining viral toxicity, innate immunity, and cell-type specificity constraints for further improvement.

Adeno-associated viral (AAV) vectors are foundational tools for dissecting brain structure-function relationships, but AAV serotype tropism varies across brain regions and species, requiring empirical validation to inform experimental design. This need is especially important in non-model organisms, where molecular neuroscience tools remain underdeveloped and access to research subjects is often limited. The Arctic ground squirrel (AGS, Urocitellus parryii) is a valuable model for studying extreme physiology, including metabolic suppression during hibernation and resistance to cerebral ischemia/reperfusion, yet no studies have evaluated AAV performance in the AGS brain. Here, we investigated the ability of AAV serotypes 1, 8, 9, and DJ to transduce the AGS hypothalamus using the human synapsin (hSyn) promoter and directly compared cellular transduction rates in a region implicated in thermoregulation and hibernation. To maximize data collection from a limited experimental population, we used a within-animal, contralateral stereotaxic injection design. Recombinant AAV vectors expressing enhanced green fluorescent protein or mCherry were delivered bilaterally, and reporter expression was analyzed four weeks later. All tested serotypes produced clear and reproducible reporter expression, establishing AAV as a viable molecular tool in the AGS hypothalamus. AAV1 produced significantly greater cellular transduction rates than AAV-DJ (17.2% {+/-} 3.5% vs 8.4% {+/-} 2.9%, paired t-test, p = 0.032). AAV8 and AAV9 showed transduction rates of 22.8% {+/-} 0.6% and 20.1% {+/-} 1.5%, respectively; however, with only two biological replicates per serotype, formal statistical comparison was not performed. These findings provide the first direct characterization of AAV-mediated gene delivery in the AGS brain and establish a foundation for future molecular interrogation of hypothalamic circuits in this extreme mammalian hibernator.

A recent study (Manjarrez et al., 2026) showed that the classification of cortical dendritic spines into stubby, thin, and mushroom subtypes is unstable under rotation. That result criticizes the categorical scheme but leaves an open question. What is the actual structure of spine morphology once the viewing angle is controlled? Here we answer it. We analyzed 228 spines from layer II pyramidal neurons in the H01 nanometer-resolution reconstruction of human temporal cortex. We first quantified the source of instability. We found that rotating dendritic segments by 90 degrees about their axes shifted the apparent spine height and head width in opposite directions across the population, thereby confirming orientation-dependent measurement error. Furthermore, to obtain measurements free of this artifact, we developed the Spine Morphometry Hub (SMH), a 12-point anatomical landmark framework that characterizes each spine in all three orthogonal planes and extracts geometric, voxel-based, and mesh-based metrics. All morphometric distributions were unimodal and right-skewed. Density-based clustering assigned most spines to noise, and a Monte-Carlo test against a discrete two-type null model confirmed that this pattern is incompatible with categorical subtypes. We also confirmed that apical and basal spines were statistically indistinguishable. Unlike previous reports of a spine continuum, all based on orientation-dependent measurements, our framework removes the viewing-angle confound itself, so the continuum we observe cannot be attributed to a projection artifact. Hence, our framework will be useful to quantify dendritic-spine remodeling in neurological disorders, in which spine shape has long been observed but never measured against an orientation-invariant morphometric standard. HighlightsO_LISpine Morphometry Hub (SMH) measures spines free of viewing-angle error C_LIO_LISMH was validated as an orientation-invariant morphometry framework C_LIO_LIRotating dendrites by 90{degrees} shifts spine height and head width oppositely C_LIO_LIAll morphometric distributions are unimodal and right-skewed, not categorical C_LIO_LISMH could be used to quantify dendritic-spine remodeling in neurological disorders C_LI

Recent studies have shown that symbiotic bacteria can have drastic effects on host neurobiology, but few simple, accessible models currently exist in which to study these interactions. Hawaiian bobtail squid (Euprymna scolopes) participate in a binary symbiosis with the bacterium Vibrio fischeri, a population of which resides in a specialized hindgut-derived organ called the light organ. Upon colonization by V. fischeri, the light organ undergoes transcriptional changes that suggest neurons are impacted by the initiation of symbiosis, but the nascent light organs innervation has remained uncharacterized. Here, we show that the light organ-associated nervous system (LONS) in hatchling E. scolopes is a remarkably complex segment of the peripheral nervous system. The LONS is largely plexiform and originates from two primary nerves connected by a local commissure. The abundance of synapsin-like immunoreactivity (-lir) indicates that the lobe plexus is highly interconnected. We also highlight a small number of serotonin-lir neurites that innervate the anterior appendages whose developmental fate may be directly affected by symbiont-driven light organ morphogenesis. Finally, we present evidence that a limited but diverse population of neurons reside within the light organ and are often located near internal symbiont-interacting structures. This description of the E. scolopes LONS serves to provide a foundation from which to investigate how beneficial bacterial symbionts affect host peripheral neurobiology in a tractable model system.

Early postnatal development is a critical period for hippocampal circuit maturation. While postnatal hippocampal development has been mostly studied in rats, less is known about the developmental trajectory of electrophysiological properties in mice, despite the wide use of these animal models for molecular and genetic studies of nervous system. In this study, we investigated the postnatal maturation of hippocampal CA1 pyramidal neurons in male and female wild-type mice. Whole-cell patch-clamp recordings were performed in acute hippocampal slices to assess passive and active membrane properties as well as spontaneous excitatory synaptic activity. We found that maturation of neuronal firing properties was associated with faster responses to stimulation, higher-amplitude and shorter-duration action potentials, and more precise control of neuronal firing. Simultaneously, synaptic activity changed across development, with decreased sEPSC inter-event intervals and stable event amplitudes, suggesting enhanced functional connectivity without major changes in synaptic strength. Sex-dependent differences in electrophysiological properties were observed primarily during the first postnatal week, indicating that sex influences the early trajectory of neuronal maturation. Together, our findings provide a comprehensive electrophysiological baseline for mouse hippocampal CA1 pyramidal neurons during postnatal development.

Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.