Biology subjects

Dayer, A.

Publications and source records attributed to Dayer, A..

12 recordsLinked to original sources

bioRxiv2026

Htr3a receptors control attenuation of fear responses by modulating the corticolimbic network activity and synchronization

The fear circuit orchestrates defensive responses to environmental threats and is essential for survival. Dysregulation of this system is thought to contribute to the pathophysiology of several psychiatric disorders. Within this fear circuit, the corticolimbic network, particularly the amygdala and the medial prefrontal cortex (mPFC), is strongly modulated by serotonin. Previous studies have shown that Htr3a knockout (Htr3a-KO) mice exhibit deficits in the extinction of cued fear memory; however, the circuit level mechanisms underlying these impairments remain unknown. Here, we investigated this question by recording local field potentials evoked by auditory conditioned stimuli (CS) in the prelimbic (PrL), infralimbic (IL), and basolateral amygdala (BLA) of head-fixed wild-type (WT) and Htr3a-KO mice prior to fear conditioning and during fear memory retrieval. Behaviorally, Htr3a-KO mice displayed a delayed attenuation of fear-induced freezing during cued fear memory retrieval, whereas WT mice showed a rapid attenuation in freezing. Electrophysiologically, Htr3a-KO mice exhibited reduced fear-evoked theta power in the PrL, IL, and BLA, along with diminished mPFC-BLA theta synchrony. Moreover, theta-phase modulation of gamma oscillations within the BLA, which has been shown to increase during fear states, was perturbed in the absence of Htr3a signaling. Together, these findings indicate that Htr3a is critical for maintaining proper oscillatory dynamics within the mPFC-BLA circuit and for supporting effective attenuation of learned fear. Highlights- Attenuation of fear responses during fear memory retrieval sessions is protracted in Htr3a knock-out mice - The fear-induced theta response in the medial prefrontal cortex and the basolateral amygdala is less powerful in the Htr3a knock-out mice than in wild-type - Htr3a knock-out mice show a deficit in fear-induced synchronization as well as in theta modulation of gamma power in the cortico-limbic network - These results suggest that malfunction of the Htr3a receptor cause alterations in fear network circuit mechanisms that might be linked to deficits in fear responses attenuation

neuroscience↗

bioRxiv2025

Neurogliaform cells mediate interhemispheric modulation of sensory-evoked activity in cortical pyramidal neurons

Integration of bilateral sensory inputs requires effective communication between brain hemispheres. This interhemispheric communication is essential for sensory perception and involves reciprocal connections between homotopic sensory areas. A key role in this process is attributed to interhemispheric inhibition which, owing to its long-lasting form, is posited to operate largely through neurogliaform cells (NGCs). However, direct evidence on the role of NGCs in interhemispheric inhibition is missing. Here we show that NGCs in the mouse barrel cortex (BC) are engaged by interhemispheric callosal projections to modulate pyramidal neuron (PN) activity and sensory perception. Using optogenetics, ex vivo whole-cell recordings, and in vivo calcium imaging, we found that layer 1 and layer 2/3 (L1-3) NGCs are strongly activated by the callosal and suppressed by the thalamocortical pathway, suggesting that NGCs encode ipsilateral rather than contralateral whisker stimuli. We also found that direct stimulation of L1-3 NGCs modulates whisker-evoked activity in L2/3 and L5b PNs, and increases the perceptual threshold in a whisker-deflection detection task. Furthermore, these effects were recapitulated by direct stimulation of callosal projections and deflection of the ipsilateral whiskers respectively, suggesting that the effect of the callosal pathway on sensory perception is mediated by NGCs. Our results not only prove that NGCs mediate interhemispheric inhibition, but also demonstrate their role in sensory perception via modulation of the main units involved in cortical input and output.

neuroscience↗

bioRxiv2024

Platelet-derived LPA16:0 inhibits adult neurogenesis and stress resilience in anxiety disorder

Anxiety disorders are accompanied by changes in brain plasticity, stress vulnerability and heightened risk of depression. Here, we found that serum LPA16:0 abundance increased with trait anxiety in both human and mice and was sufficient to reduce the proliferation of adult hippocampal neural stem/progenitor cells. In humans, the main LPA receptor, LPA1, bears single nucleotide polymorphism variants associated with anxiety. In mice, LPA16:0 decreased hippocampal neurogenesis and stress resilience, whereas LPA1 antagonism or the reduction of platelets, the main source of circulating LPA16:0, increased adult neurogenesis and resilience to acute stress. Finally, the inhibition of adult neurogenesis abolished the beneficial effect of LPA1 antagonism on resilience against both acute and chronic stress. Together, these findings identify LPA16:0-LPA1 signaling as a regulation mechanism of adult neurogenesis and a potential therapeutic target for mood disorders.

neuroscience↗

bioRxiv2024

The collective application of shorebird tracking data to conservation

Addressing urgent conservation issues, like the drastic declines of North American migratory birds, requires creative, evidence-based, efficient, and collaborative approaches. Over 50% of monitored North American shorebird populations have lost over 50% of their abundance since 1980. To address these declines, we developed a partnership of scientists and practitioners called the Shorebird Science and Conservation Collective (hereinafter "the Collective"). Here, we present this successful case study as an example for others engaged in translational science. The Collective acts as an intermediary whereby dedicated staff collate and analyze data contributions from scientists to support knowledge requests from conservation practitioners. Data contributions from 74 organizations include over 6.7 million shorebird locations forming movement paths of 3,345 individuals representing 36 species tracked across the Americas. We describe the founding and structure of the Collective and conservation activities we supported in our first two years. As the volume of scientific data on animal movements continues to grow, groups like the Collective can be vital liaisons to rapidly integrate and interpret research to support conservation action.

ecology↗

bioRxiv2021

Dysfunctional temporal stages of eye-gaze perception in adults with ADHD: a high-density EEG study

ADHD have been associated with social cognitive impairments across the lifespan, but no studies have specifically addressed the presence of abnormalities in eye-gaze processing in the adult brain. This study investigated the neural basis of eye-gaze perception in adults with ADHD using event-related potentials (ERP). Twenty-three ADHD and 23 controls performed a delayed face-matching task with neutral faces that had either direct or averted gaze. ERPs were classified using microstate analyses. ADHD and controls displayed similar P100 and N170 microstates. ADHD was associated with cluster abnormalities in the attention-sensitive P200 to direct gaze, and in the N250 related to facial recognition. For direct gaze, source localization revealed reduced activity in ADHD for the P200 in the left/midline cerebellum, as well as in a cingulate-occipital network at the N250. These results suggest brain impairments involving eye-gaze decoding in adults with ADHD, suggesting that neural deficits persist across the lifespan.

neuroscience↗

bioRxiv2021

MiR-137 and miR-122, two outer subventricular zone-enriched non-coding RNAs, regulate basal progenitor expansion and neuronal differentiation

Cortical expansion in the primate brain relies on the presence and the spatial enlargement of multiple germinal zones during development and on a prolonged developmental period. In contrast to other mammals, which have two cortical germinal zones, the ventricular zone (VZ) and subventricular zone (SVZ), gyrencephalic species display an additional germinal zone, the outer subventricular zone (OSVZ), which role is to increase the number and types of neurons generated during corticogenesis. How the OSVZ emerged during evolution is poorly understood but recent studies suggest a role for non-coding RNAs, which allow tight regulations of transcriptional programs in time and space during development (Dehay et al. 2015; Arcila et al., 2014). Here, using in vivo functional genetics, single-cell RNA sequencing, live imaging and electrophysiology to assess progenitor and neuronal properties in mice, we identify two ferret and human OSVZ-enriched microRNAs (miR), miR-137 and miR-122, which regulate key cellular features associated with cortical expansion. MiR-137 promotes basal progenitor self-replication and superficial layer neuron fate, while miR-122 slows down neuronal differentiation pace. Together, these findings support a cell-type specific role for miR-mediated transcriptional regulation in cortical expansion.

evolutionary biology↗

bioRxiv2020

PlexinA4-Semaphorin3A mediated crosstalk between main cortical interneuron classes is required for superficial interneurons lamination

In the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory interneurons (INs) into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A+) cortical INs (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4. We identify that deep layer INs constitute a major source of SEMA3A in the developing cortex and demonstrate that cell-type specific genetic deletion of SEMA3A in these INs specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer INs control the laminar allocation of hINs into superficial layers.

neuroscience↗

bioRxiv2019

MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination

The combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction is unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the MCF2 gene in a boy with CBPS. Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse Mcf2 gene controls the embryonic migration of cortical projection neurons. Strikingly, we find that the CBPS-associated MCF2 mutation impairs cortical laminar positioning, supporting the hypothesis that alterations in the process of embryonic neuronal migration can lead to rare cases of CBPS.

neuroscience↗

bioRxiv2019

Linking alpha oscillations, attention and inhibitory control in adult ADHD with EEG neurofeedback

Abnormal patterns of electrical oscillatory activity have been repeatedly described in adult ADHD. In particular, the alpha rhythm (8-12 Hz), known to be modulated during attention, has previously been considered as candidate biomarker for ADHD. In the present study, we asked adult ADHD patients to self-regulate their own alpha rhythm using neurofeedback (NFB), in order to examine the modulation of alpha oscillations on attentional performance and brain plasticity. Twenty-five adult ADHD patients and 22 healthy controls underwent a 64-channel EEG-recording at resting-state and during a Go/NoGo task, before and after a 30 min-NFB session designed to reduce (desynchronize) the power of the alpha rhythm. Alpha power was compared across conditions and groups, and the effects of NFB were statistically assessed by comparing behavioral and EEG measures pre-to-post NFB. Firstly, we found that relative alpha power was attenuated in our ADHD cohort compared to control subjects at baseline and across experimental conditions, suggesting a signature of cortical hyper-activation. Both groups demonstrated a significant and targeted reduction of alpha power during NFB. Interestingly, we observed a post-NFB increase in resting-state alpha (i.e. rebound) in the ADHD group, which restored alpha power towards levels of the normal population. Importantly, the degree of post-NFB alpha normalisation during the Go/NoGo task correlated with individual improvements in motor inhibition (i.e. reduced commission errors and slower reaction times in NoGo trials) only in the ADHD group. Overall, our findings offer novel supporting evidence implicating alpha oscillations in inhibitory control, as well as their potential role in the homeostatic regulation of cortical excitatory/inhibitory balance.\n\nHighlightsO_LIResting alpha power is reduced in adult ADHD suggesting cortical hyper-activation\nC_LIO_LIAdult ADHD patients successfully reduce alpha power during neurofeedback\nC_LIO_LIA post-neurofeedback rebound normalizes alpha power in adult ADHD\nC_LIO_LIAlpha power rebound correlates with improvement of inhibitory control in adult ADHD\nC_LI

neuroscience↗

bioRxiv2019

Deviant EEG resting-state large-scale brain network dynamics in euthymic bipolar disorder patients

BackgroundNeuroimaging studies provided evidence for disrupted resting-state functional brain network activity in bipolar disorder (BD). Electroencephalographic (EEG) studies found altered temporal characteristics of functional EEG microstates during depressive episode within different affective disorders. Here we investigated whether euthymic patients with BD show deviant resting-state large-scale brain network dynamics as reflected by altered temporal characteristics of EEG microstates.\n\nMethodsWe used high-density EEG to explore between-group differences in duration, coverage and occurrence of the resting-state functional EEG microstates in 17 euthymic adults with BD in on-medication state and 17 age- and gender-matched healthy controls. Two types of anxiety, state and trait, were assessed separately with scores ranging from 20 to 80.\n\nResultsMicrostate analysis revealed five microstates (A-E) in global clustering across all subjects. In patients compared to controls, we found increased occurrence and coverage of microstate A that did not significantly correlate with anxiety scores.\n\nConclusionOur results provide neurophysiological evidence for altered large-scale brain network dynamics in BD patients and suggest the increased presence of A microstate to be an electrophysiological trait characteristic of BD.

neuroscience↗

bioRxiv2018

Single-cell transcriptional dynamics and origins of neuronal diversity in the developing mouse neocortex

During cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. The neurogenic competence of these progenitors progresses as corticogenesis proceeds; likewise, newborn neurons transit through sequential states as they differentiate. Here, we trace the developmental transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons using parallel single-cell RNA sequencing between embryonic day (E) 12 and E15 in the mouse cerebral cortex. Our results identify the birthdate- and differentiation stage-related transcriptional dynamics at play during corticogenesis. As corticogenesis proceeds, APs transit through embryonic age-dependent molecular states, which are transmitted to their progeny to generate successive initial daughter cell identities. In neurons, essentially conserved post-mitotic differentiation programs are applied onto these distinct AP-derived ground states, allowing temporally-regulated sequential emergence of specialized neuronal cell types. Molecular temporal patterning of sequentially-born daughter neurons by their respective mother cell thus underlies emergence of neuronal diversity in the neocortex.\n\nOne Sentence SummaryDuring corticogenesis, temporally dynamic molecular birthmarks are transmitted from progenitors to their post-mitotic progeny to generate neuronal diversity.

neuroscience↗

bioRxiv2018

Single-cell molecular connectomics of intracortically-projecting neurons

The neocortex is organized into distinct areas, whose interconnectivity underlies sensorimotor transformations and integration1-7. These behaviorally critical functions are mediated by intracortically-projecting neurons (ICPN), which are a heterogeneous population of cells sending axonal branches to distinct cortical areas as well as to subcortical targets8-10. Although population-based11-14 and single-cell15-19 intracortical wiring diagrams are being identified, the transcriptional signatures corresponding to single-cell axonal projections of ICPN to multiple sites remain unknown. To address this question, we developed a high-throughput approach, \"ConnectID\", to link connectome and transcriptome in single neurons. ConnectID combines MAPseq projection mapping17,20 (to identify single-neuron multiplex projections) with single-cell RNA sequencing (to identify corresponding gene expression). Using primary somatosensory cortex (S1) ICPN as proof-of-principle neurons, we identify three cardinal targets: (1) the primary motor cortex (M1), (2) the secondary somatosensory cortex (S2) and (3) subcortical targets (Sub). Using ConnectID, we identify transcriptional modules whose combined activities reflect multiplex projections to these cardinal targets. Based on these findings, we propose that the combinatorial activity of connectivity-defined transcriptional modules serves as a generic molecular mechanism to create diverse axonal projection patterns within and across neuronal cell types.

neuroscience↗