Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM(+)) CeL neurons, which has previously been shown to store fear memory. Consistently, we found that PVT neurons preferentially innervate SOM(+) neurons in the CeL, and stimulation of PVT afferents facilitated SOM(+) neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM(+) CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnf in the PVT or Trkb in SOM(+) CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.

Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.

Inhibition is critical for controlling information transfer in the brain. However, the understanding of the plasticity and particular function of different interneuron subtypes is just emerging. Using acute hippocampal slices prepared from adult mice, we report that in area CA2 of the hippocampus, a powerful inhibitory transmission is acting as a gate to prevent CA3 inputs from driving CA2 neurons. Furthermore, this inhibition is highly plastic, and undergoes a long-term depression following high-frequency 10 Hz or theta-burst induction protocols. We describe a novel form of long-term depression at parvalbumin-expressing (PV+) interneuron synapses that is dependent on delta-opioid receptor (DOR) activation. Additionally, PV+ interneuron transmission is persistently depressed by DOR activation in area CA2 but only transiently depressed in area CA1. These results provide evidence for a differential temporal modulation of PV+ synapses between two adjacent cortical circuits, and highlight a new function of PV+ cells in controlling information transfer.

Four mosquito species, including a new species of the genus Stegomyia, are reported from Mayotte in the western Indian Ocean. The most abundant species were Stegomyia aegypti and St. albopicta. Only one species of the St. simpsoni group was observed, St. bromeliae. The fourth species is Stegomyia pia Le Goff & Robert n. sp. of which the larva, pupa, male and female are here described. The larval stages of St. pia n. sp. are morphologically similar to St. aegypti but differ in the number of branches of the seta 1-X; the adult is morphologically distinct for a number of characters, for instance the scutal ornamentation. Stegomyia pia n. sp. is uncommon but not rare, and largely distributed across Mayotte. Its larval habitats are natural and diverse including rock pools, tree holes, and cut and severed bamboos. The biology of adults remains unknown, especially female biting behaviour. Both morphological characters and nucleotide sequences of the ITS2 and COI genes indicate that this species is best placed in the genus Stegomyia. Dichotomous keys to the four species of Mayotte Stegomyia are presented for adults and fourth-instar larvae. The potential vector role of these mosquitoes is hypothesised. This paper underlines advances in knowledge of the biodiversity in the French overseas departments and territories.

Area CA2 is emerging as an important region for hippocampal memory formation. However, how CA2 pyramidal neurons (PNs) are engaged by intrahippocampal inputs remains unclear. Excitatory transmission between CA3 and CA2 is strongly inhibited and is not plastic. We show in mice that different patterns of activity can in fact increase the excitatory drive between CA3 and CA2. We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology. In addition, we show that the net excitatory drive of distal inputs is also increased after iLTD induction. The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs. Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.

An identification key of the Phlebotomus in Madagascar is proposed as well as the description of the male and female Phlebotomus (Anaphlebotomus) vaomalalae n. sp. from Mikea Forest in the south-west of Madagascar. The assignation of this new species to the genus Phlebotomus is based on the presence of mesanepisternal setae. Its inclusion in the subgenus Anaphlebotomus is based on the males on the presence of four spines on the style, the lack of a coxite basal process and the existence of a bifurcated paramere. The female has cibarial and pharyngeal armature and spermathecal architecture similar to Phlebotomus fertei and Phlebotomus berentiensis, two other Malagasy species which belong to Anaphlebotomus. Male and female are held to belong to the same species because of their morphological characters, the homology (100%) of their partial cytochrome b mtDNA sequences and their capture in the same trap. P. vaomalalae n. sp. is a small species compared to the other Phlebotomus species of Madagascar. The cibarium of the male and the female of P. vaomalalae n. sp. is armed with teeth, like those of other Malagasy Phlebotomus. However, it differs in the arrangement and shape of the respective teeth and denticles. The male of P. vaomalalae n. sp. looks like that of P. fontenillei due to its tuft of coxal setae (lacking in P. berentiensis and P. fertei) but differs from this species by the location of this tuft. As P. fertei and P. berentiensis, there is no spermathecal common duct in P. vaomalalae n. sp.

The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.

In the context of One Health, there is presently an effort to integrate surveillance of human, animal, entomological, and environmental sectors. This aims to strengthen the prevention of, and preparedness against, arbovirus infections, also in the light of environmental and climate changes that could increase the risk of transmission. However, criteria to define integrated surveillance, and to compare different systems, still need to be identified and tested. We conducted a scoping review to identify and examine surveillance systems for West Nile virus (WNV), chikungunya virus (CHKV), dengue virus (DENV), and Rift Valley fever virus (RVFV), which involve human, animal, entomological, and environmental sectors. We analyzed findings using a conceptual framework we developed for this purpose. The review highlights that the criteria proposed in the conceptual framework to describe integrated surveillance are consistently reported in the context of studies and programs related to integrated surveillance of the selected arboviral diseases. These criteria can facilitate the identification and description of operationalized One Health surveillance.

Adolescence is a vulnerable period characterized by major cognitive changes. The mechanisms underlying the emergence of new cognitive functions are poorly understood. We find that a long-term depression of inhibitory transmission (iLTD) from parvalbumin-expressing (PV+) interneurons in the hippocampal area Cornu Ammonis 2 (CA2) is absent in young mice but emerges at the end of adolescence. We demonstrate that the maturation of both the perineuronal net (PNN) and signaling through ErbB4 is required for this plasticity. Furthermore, we demonstrate that social recognition memory displays the same age dependence as iLTD and is impaired by targeted degradation of the PNN or iLTD blockade in area CA2. Our data reveal an unusual developmental rule for plasticity at the PV+ interneuron transmission in area CA2 and indicate that this plasticity is involved in the emergence of higher cognitive function, such as social memory formation, in late adolescence.

Emotionally salient information activates orexin neurons in the lateral hypothalamus, leading to increase in sympathetic outflow and vigilance level. How this circuit alters animals' behavior remains unknown. Here we report that noradrenergic neurons in the locus coeruleus (NALC neurons) projecting to the lateral amygdala (LA) receive synaptic input from orexin neurons. Pharmacogenetic/optogenetic silencing of this circuit as well as acute blockade of the orexin receptor-1 (OX1R) decreases conditioned fear responses. In contrast, optogenetic stimulation of this circuit potentiates freezing behavior against a similar but distinct context or cue. Increase of orexinergic tone by fasting also potentiates freezing behavior and LA activity, which are blocked by pharmacological blockade of OX1R in the LC. These findings demonstrate the circuit involving orexin, NALC and LA neurons mediates fear-related behavior and suggests inappropriate excitation of this pathway may cause fear generalization sometimes seen in psychiatric disorders, such as PTSD.

Anopheles multicolor is known to be present in the arid areas of Africa north of the Sahara Desert, especially in oases. To date, its presence in Mauritania has not been reported. Here, we present the first record of its presence in Nouakchott, the capital of Mauritania. The larvae of An. multicolor, together with those of An. arabiensis, the major malaria vector in the city, were found thriving in highly saline surface water collections.

p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.

The hippocampus is critical for the formation of episodic memory. It is, therefore, important to understand intra-hippocampal circuitry, especially in the often overlooked area CA2. Using specific transgenic mouse lines combined with opto- and chemogenetics, we show that local plasticity of parvalbumin-expressing interneurons in area CA2 allows CA3 input to recruit CA2 pyramidal neurons (PNs), thereby increasing the excitatory drive between CA3 and CA1. CA2 PNs provide both stronger excitation and larger feed-forward inhibition onto deep, compared with superficial, CA1 PNs. This feed-forward inhibition, largely mediated by parvalbumin-expressing interneurons, normalizes the excitatory drive onto deep and superficial CA1 PNs. Finally, we identify a target of CA2 in area CA1, i.e., CA1 PNs, whose soma are located in stratum radiatum. These data provide insight into local hippocampal circuitry and reveal how localized plasticity can potentially control information flow in the larger hippocampal network.

In the hippocampal circuit CA3 input plays a critical role in the organization of CA1 population activity, both during learning and sleep. While integrated spatial representations have been observed across the two hemispheres of CA1, these regions lack direct connectivity and thus the circuitry responsible remains largely unexplored. Here we investigate the role of CA3 in organizing bilateral CA1 activity by blocking synaptic transmission at CA3 terminals through the inducible transgenic expression of tetanus toxin. Although the properties of single place cells in CA1 were comparable bilaterally, we find a decrease of ripple synchronization between left and right CA1 after silencing CA3. Further, during both exploration and rest, CA1 neuronal ensemble activity is less coordinated across hemispheres. This included degradation of the replay of previously explored spatial paths in CA1 during rest, consistent with the idea that CA3 bilateral projections integrate activity between left and right hemispheres and orchestrate bilateral hippocampal coding.

A report of a family of Darier's disease with mood disorders drew attention when the causative gene was identified as ATP2A2 (or SERCA2), which encodes a Ca2+ pump on the endoplasmic reticulum (ER) membrane and is important for intracellular Ca2+ signaling. Recently, it was found that loss-of-function mutations of ATP2A2 confer a risk of neuropsychiatric disorders including depression, bipolar disorder and schizophrenia. In addition, a genome-wide association study found an association between ATP2A2 and schizophrenia. However, the mechanism of how ATP2A2 contributes to vulnerability to these mental disorders is unknown. Here, we analyzed Atp2a2 heterozygous brain-specific conditional knockout (hetero cKO) mice. The ER membranes prepared from the hetero cKO mouse brain showed decreased Ca2+ uptake activity. In Atp2a2 heterozygous neurons, decays of cytosolic Ca2+ level were slower than control neurons after depolarization. The hetero cKO mice showed altered behavioral responses to novel environments and impairments in fear memory, suggestive of enhanced dopamine signaling. In vivo dialysis demonstrated that extracellular dopamine levels in the NAc were indeed higher in the hetero cKO mice. These results altogether indicate that the haploinsufficiency of Atp2a2 in the brain causes prolonged cytosolic Ca2+ transients, which possibly results in enhanced dopamine signaling, a common feature of mood disorders and schizophrenia. These findings elucidate how ATP2A2 mutations causing a dermatological disease may exert their pleiotropic effects on the brain and confer a risk for mental disorders.

The BTBR T+Itpr3tf/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.

The structured reactivation of hippocampal neuronal ensembles during fast synchronous oscillatory events, termed sharp-wave ripples (SWRs), has been suggested to play a crucial role in the storage and use of memory. Activity in both the CA2 and CA3 subregions can precede this population activity in CA1, and chronic inhibition of either region alters SWR oscillations. However, the precise contribution of CA2 to the oscillation, as well as to the reactivation of CA1 neurons within it, remains unclear. Here, we employ chemogenetics to transiently silence CA2 pyramidal cells in mice, and we observe that although SWRs still occur, the reactivation of CA1 pyramidal cell ensembles within the events lose both temporal and informational precision. These observations suggest that CA2 activity contributes to the fidelity of experience-dependent hippocampal replay.

The mosquito species Aedes (Ochlerotatus) coluzzii Rioux, Guilvard & Pasteur, 1998 was distinguished from its sibling species Aedes detritus (Haliday, 1833) using an isoenzymatic method that required the destruction of the entire specimen, therefore no holotype was designated by the species authors. We aimed to designate a neotype for Ae. coluzzii from specimens collected from the type-locality and individually reared up to adult stage. Genomic DNA was extracted from pupal exuvia and ITS2 was sequenced, enabling verification of the identity of each specimen as Ae. coluzzii or Ae. detritus. Among the series of Ae. coluzzii, a male was designated as neotype and deposited in a collection. To our knowledge, this is the first time the type of a mosquito species is deposited thanks to its molecular identification from its pupal exuvia. The set of identified specimens allowed additional phylogenetic and morphologic studies.

Social animals become stressed upon social isolation, proactively engaging in affiliative contacts among conspecifics after resocialization. We have previously reported that calcitonin receptor (Calcr) expressing neurons in the central part of the medial preoptic area (cMPOA) mediate contact-seeking behaviors in female mice. Calcr neurons in the posterodorsal part of the medial amygdala (MeApd) are also activated by resocialization, however their role in social affiliation is still unclear. Here we first investigated the functional characteristics of MeApd Calcr + cells; these neurons are GABAergic and show female-biased Calcr expression. Next, using an adeno-associated virus vector expressing a short hairpin RNA targeting Calcr we aimed to identify its molecular role in the MeApd. Inhibiting Calcr expression in the MeApd increased social contacts during resocialization without affecting locomotor activity, suggesting that the endogenous Calcr signaling in the MeApd suppresses social contacts. These results demonstrate the distinct roles of Calcr in the cMPOA and MeApd for regulating social affiliation.

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi. Database URL: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353.