Biology subjects

Francesconi, W.

Publications and source records attributed to Francesconi, W..

4 recordsLinked to original sources

bioRxiv2024

Like sisters but not twins - vasopressin and oxytocin excite BNST neurons via cell type-specific expression of oxytocin receptor to reduce anxious arousal

Interoceptive signals dynamically interact with the environment to shape appropriate defensive behaviors. Hypothalamic hormones arginine-vasopressin (AVP) and oxytocin (OT) regulate physiological states, including water and electrolyte balance, circadian rhythmicity, and defensive behaviors. Both AVP and OT neurons project to dorsolateral bed nucleus of stria terminalis (BNSTDL), which expresses oxytocin receptors (OTR) and vasopressin receptors and mediates fear responses. However, understanding the integrated role of neurohypophysial hormones is complicated by the cross-reactivity of AVP and OT and their mutual receptor promiscuity. Here, we provide evidence that the effects of neurohypophysial hormones on BNST excitability are driven by input specificity and cell type-specific receptor selectivity. We show that OTR-expressing BNSTDL neurons, excited by hypothalamic OT and AVP inputs via OTR, play a major role in regulating BNSTDL excitability, overcoming threat avoidance, and reducing threat-elicited anxious arousal. Therefore, OTR-BNSTDL neurons are perfectly suited to drive the dynamic interactions balancing external threat risk and physiological needs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/611656v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@2c800forg.highwire.dtl.DTLVardef@18b5cfaorg.highwire.dtl.DTLVardef@85324aorg.highwire.dtl.DTLVardef@a8bb6b_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIExogenous and light-evoked vasopressin (AVP) peptide excites neurons of the bed nucleus of the stria terminalis (BNST) via oxytocin receptor (OTR) in male rats C_LIO_LIAVP excites OTR- and Corticotropin-releasing factor (CRF)-expressing neurons, most of which are classified as Type III neurons of the BNST C_LIO_LIOTR-expressing BNST neurons increase exploration of open spaces and reduce anxious arousal in fear-potentiated startle in male rats C_LIO_LIThe dorsolateral BNST receives vasopressinergic inputs from suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus C_LIO_LIInternal signal-sensitive hypothalamic inputs directly impact BNST excitability via OTR to balance interoceptive signals and defensive behaviors C_LI

neuroscience↗

bioRxiv2023

Coupling remote sensing and eDNA to monitor environmental impact: A pilot to quantify the environmental benefits of sustainable agriculture in the Brazilian Amazon

Monitoring is essential to ensure that environmental goals are being achieved, including those of sustainable agriculture. Growing interest in environmental monitoring provides an opportunity to improve monitoring practices. Approaches that directly monitor land cover change and biodiversity annually by coupling the wall-to-wall coverage from remote sensing and the site-specific community composition from environmental DNA (eDNA) can provide timely, relevant results for parties interested in the success of sustainable agricultural practices. To ensure that the measured impacts are due to the environmental projects and not exogenous factors, sites where projects have been implemented should be benchmarked against counterfactuals (no project) and control (natural habitat) sites. Results can then be used to calculate diverse sets of indicators customized to monitor different projects. Here, we report on our experience developing and applying one such approach to assess the impact of shaded cocoa projects implemented by the Instituto de Manejo e Certificacao Florestal e Agricola (IMAFLORA) near Sao Felix do Xingu, in Para, Brazil. We used the Continuous Degradation Detection (CODED) and LandTrendr algorithms to create a remote sensing-based assessment of forest disturbance and regeneration, estimate carbon sequestration, and changes in essential habitats. We coupled these remote sensing methods with eDNA analyses using arthropod-targeted primers by collecting soil samples from intervention and counterfactual pasture field sites and a control secondary forest. We used a custom set of indicators from the pilot application of a coupled monitoring framework called TerraBio. Our results suggest that, due to IMAFLORAs shaded cocoa projects, over 400 acres were restored in the intervention area and the community composition of arthropods in shaded cocoa is closer to second-growth forests than that of pastures. In reviewing the coupled approach, we found multiple aspects worked well, and we conclude by presenting multiple lessons learned.

ecology↗

bioRxiv2020

Oxytocin selectively excites interneurons and inhibits output neurons of the bed nucleus of the stria terminalis (BNST)

The dorsolateral bed nucleus of the stria terminalis (BNSTDL) has high expression of oxytocin (OT) receptors (OTR), which were shown to facilitate cued fear. However, the role of OTR in the modulation of BNSTDL activity remains elusive. BNSTDL contains GABA-ergic neurons classified based on intrinsic membrane properties into three types. Using in vitro patch-clamp recordings in male rats, we demonstrate that OT selectively excites and increases spontaneous firing rate of Type I BNSTDL neurons. As a consequence, OT increases the frequency, but not amplitude, of spontaneous inhibitory post-synaptic currents (sIPSCs) selectively in Type II neurons, an effect abolished by OTR antagonist or tetrodotoxin, and reduces spontaneous firing rate in these neurons. These results suggest an indirect effect of OT in Type II neurons, which is mediated via OT-induced increase in firing of Type I interneurons. As Type II BNSTDL neurons were shown projecting to the central amygdala (CeA), we also recorded from retrogradelly labeled BNST[->]CeA neurons and we show that OT increases the frequency of sIPSC in these Type II BNST[->]CeA output neurons. In contrast, in Type III neurons, OT reduces the amplitude, but not frequency, of both sIPSCs and evoked IPSCs via a postsynaptic mechanism without changing their intrinsic excitability. We present a model of fine-tuned modulation of BNSTDL activity by OT, which selectively excites BNSTDL interneurons and inhibits Type II BNST[->]CeA output neurons. These results suggest that OTR in the BNST might facilitate cued fear by inhibiting the BNST[->]CeA neurons. HighlightsO_LIOxytocin directly excites and increases spontaneous firing of Type I BNST interneurons C_LIO_LIOxytocin indirectly inhibits Type II BNST neurons C_LIO_LIOxytocin inhibits Type II BNST output neurons to the central amygdala (BNST[->]CeA) C_LIO_LIOxytocin reduces GABA-ergic transmission in Type III BNST neurons C_LIO_LIOxytocin might facilitate cued fear by inhibiting the Type II BNST[->]CeA neurons C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/169466v3_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@134326dorg.highwire.dtl.DTLVardef@1dad252org.highwire.dtl.DTLVardef@1263dd6org.highwire.dtl.DTLVardef@1a5c9e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

NMDA Receptor Dysregulation by Defective Depalmitoylation in the Infantile Neuronal Ceroid Lipofuscinosis Mouse Model

Protein palmitoylation and depalmitoylation alter protein function. This post-translational modification is critical for synaptic transmission and plasticity. Mutation of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) causes infantile neuronal ceroid lipofuscinosis (CLN1), a pediatric neurodegenerative disease. However, the role of protein depalmitoylation in synaptic maturation is unknown. Therefore, we studied synapse development in Ppt1-/- mouse visual cortex. We demonstrate the stagnation of the developmental N-methyl-D-aspartate receptor (NMDAR) subunit switch from GluN2B to GluN2A in Ppt1-/- mice. Correspondingly, GluN2A-mediated synaptic currents are diminished and Ppt1-/- dendritic spines maintain immature morphology in vivo. Further, GluN2B is hyperpalmitoylated in Ppt1-/- neurons and associated with extrasynaptic, diffuse calcium influxes and enhanced vulnerability to NMDA-induced excitotoxicity. Remarkably, Ppt1-/- neurons treated with palmitoylation inhibitors demonstrate normalized levels of palmitoylated GluN2B and Fyn kinase, reversing susceptibility to excitotoxic insult. Thus, depalmitoylation of GluN2B by PPT1 plays a critical role in postsynapse maturation and pathophysiology of neurodegenerative disease.

neuroscience↗