Neural computation involves diverse types of GABAergic inhibitory interneurons that are integrated with excitatory (E) neurons into precisely structured circuits. To understand how each neuron type ...shapes sensory representations, we measured firing patterns of defined types of neurons in the barrel cortex while mice performed an active, whisker-dependent object localization task. Touch excited fast-spiking (FS) interneurons at short latency, followed by activation of E neurons and somatostatin-expressing (SST) interneurons. Touch only weakly modulated vasoactive intestinal polypeptide-expressing (VIP) interneurons. Voluntary whisker movement activated FS neurons in the ventral posteromedial nucleus (VPM) target layers, a subset of SST neurons and a majority of VIP neurons. Together, FS neurons track thalamic input, mediating feedforward inhibition. SST neurons monitor local excitation, providing feedback inhibition. VIP neurons are activated by non-sensory inputs, disinhibiting E and FS neurons. Our data reveal rules of recruitment for interneuron types during behavior, providing foundations for understanding computation in cortical microcircuits.
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•Spikes were recorded from cortical E, FS, SST, and VIP neurons during active touch•Whisking and touch activate FS neurons in the VPM thalamorecipient layers•Touch activates SST neurons with a delay•VIP neurons are excited during whisking
Yu et al. measured the firing patterns of three major types of GABAergic inhibitory interneurons in the somatosensory cortex of mice during active tactile sensation. These cell types are recruited with distinct millisecond-scale dynamics, revealing cell-type-specific interactions and functions.
Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory ...circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP+ INs and computational modeling further showed that VIP+ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning.
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•Ca2+ imaging indicates bimodal activity dynamics of VIP interneurons in vivo•Activity of VIP interneurons is modulated by task and learning demands•VIP-mediated disinhibition supports spatially guided reward learning
Turi et al. imaged activity of VIP-expressing interneurons of hippocampal area CA1 in vivo. They show learning-related reorganization in VIP population dynamics. VIP interneurons provide behavioral state-dependent disinhibition for CA1 pyramidal cells that supports spatial reward learning.
•The kapok fiber VIP was green, degradable and nonpetroleum-based.•Hollow structure and porosity of fibres retained in wet forming process.•The thermal conductivity of kapok fiber VIP was as lower as ...6.12 mW/(m·K).•Thermal conductivity of VIPs insensitive to temperature change.
Vacuum insulation panel (VIP) is a new type of thermal insulation material with ultra-low thermal conductivity. Most of the VIP core materials are petroleum based, which helps achieve good thermal insulation performance and long service life. However, high cost and poor sustainability are not conducive to the long-term development of this industry. In this study, a new strategy is developed to prepare VIP core materials by using light, eco-friendly, and renewable kapok fibres. The results show that the wet forming process of the kapok fibre core material can maintain their hollow structure of the fibre and the porosity of VIP core could reach above 94%. The prepared kapok fibre VIPs have excellent thermal insulation performance and the thermal conductivity was as lower as 6.12 mW/(m·K) at an internal pressure of 0.05 Pa. Furthermore, these VIPs have outstanding stable thermal performance, and thermal conductivity increased only by 9–13% when the ambient temperature increased from 15 to 55 °C. The VIP density is lower than 105 kg/m3 due to the special thin-walled and large cavity structure of kapok fibres. It was confirmed that kapok fibres are a potential alternative to fume silica for super novel VIPs that are green, renewable, and eco-friendly with sustainable performance.
We explored to what extent two theoretical approaches – general (i.e., the Value-Identity-Personal norm model), and behavior-specific (i.e., the Comprehensive Action Determination Model) can explain ...different waste prevention behaviors. In Study 1 we investigated bottled water consumption, while in Study 2 we investigated bag reuse when shopping, giving away or selling unused items, and purchasing unpackaged goods. The results of Study 1 (349 adolescents from 13 to 18 years of age (54.7% were female), convenience sample) and Study 2 (508 adolescents from 13 to 17 years of age (49% were female), nationally representative random sample) indicated that both approaches predict behaviors substantially well. Among other factors, biospheric values, environmental self-identity, social norm, personal norm, and habit were found to be the most prominent contributors for their models. Both general and behavior-specific approaches have value in informing policies for lowering adolescents’ waste generation and potentially could be used in tandem.
•VIP predicted from 34% to 48% of behavioral variance; CADM predicted from 47% to 59%.•VIP and CADM models have different uses and applications.•Personal norm, a shared predictor in both VIP and CADM, was consistently significant.
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In mesial temporal lobe epilepsy (MTLE), seizures typically arise in the hippocampus or other mesial temporal lobe structures. The aetiology of MTLE epileptogenesis in still unknown, ...yet putative precipitating events such as trauma, complex febrile seizures, status epilepticus, inflammatory insults, or ischemia have been implicated. MTLE is commonly associated to a high degree of hippocampal sclerosis (HS) leading to frequent anti-epileptic drug refractoriness. Thus, the aim of recent therapeutic strategies has shifted from control of symptomatic seizures to putative prevention of epileptogenic processes. Vasoactive intestinal peptide (VIP) acts as a neurotransmitter, neurotrophic or neuroprotective factor in the central nervous system (CNS), also displaying anti-inflammatory and neurogenic actions. In the hippocampus, a brain area implicated in learning and memory, VIP released from basket cells and/or interneuron-selective interneurons controls GABAergic transmission and pyramidal cell activity influencing hippocampal-dependent synaptic plasticity (long-term potentiation and long-term depression) and cognition. VPAC1 receptor activation enhances hippocampal synaptic transmission by fostering disinhibition, while stimulation of VPAC2 receptors favours pyramidal cell excitability. Interestingly, VIP released from interneurons has potent anti-inflammatory actions, participates in the maintenance of the blood-brain barrier integrity, and strengthens neurogenesis. VPAC1 and VPAC2 receptors play differential roles in the regulation of the neuro-immune interactions. In this context, we gathered here the available information concerning the impact of VIP on neurotransmission and neuronal excitability in MTLE-HS and discuss the preventive use of selective VIP receptor ligands to abrogate epileptogenesis in MTLE-HS by controlling synaptic plasticity, neurogenesis and neuronal survival, neuroinflammation, and blood-brain barrier damage.
VIP and its receptors (VPACRs) are largely investigated in vertebrate testis, as well as their functions in the control of spermatogenesis and steroidogenesis. By contrast, a few data are available ...about the presence and role of VIP in the epididymis. The aim of the present paper was to investigate the localization of VIP and its receptors in the epididymis of two vertebrates: Podarcis sicula, a seasonal reproducer, and Rattus rattus, a continuous reproducer. By immunohystochemical investigation, we demonstrated for the first time that VIP and its receptors are widely represented in the epididymis of Podarcis sand Rattus; in particular in Podarcis, we showed that during the reproductive period, as well as in Rattus, VIP and its receptors are well represented in all the epithelial cells and the connective tissue of the epididymis; by contrast, during the non-reproductive period, VIP and its receptors are represented only in the connective tissue. The possible role of the VIP/VPACR system in the control of reproduction is discussed.
•The primary driver of ETa tendencies was vegetation greening in Yangtze and Mekong, and climate change in other basins.•The dominant factors impact ETa shifted from precipitation in Mississippi, ...Murray-Darling and Nile to radiation in Amazon.•The occurrences of drought in the Amazon basin and Murray-Darling basin corresponded strongly with El Niño events.
Accurately quantifying the impacts of climate change on global hydrological cycles is essential for water resource management. Integrated with the Global Land Surface Satellite (GLASS) leaf area index (LAI), the actual evapotranspiration (ETa) from 1981 to 2012 in eight major river basins (Amazon, Mississippi, Yangtze, Mekong, Lena, Murray-Darling, Nile, and Rhine) was simulated with the VIP (Vegetation Interface Processes) ecohydrological dynamic model. The sensitivities and contributions of ETa to climatic change and vegetation greening were explored with the elasticity coefficient method. The results showed that the simulated monthly ETa was consistent with the eddy covariance measurements (determination coefficient (R2) ranged from 0.5 to 0.85, p < 0.01). The simulated annual ETa was also in good agreement with those from the annual water balance (R2 = 0.89, p < 0.01) across the eight basins. The relative annual ETa trends in the Amazon and Mississippi basins were negative, approximately −0.09 % year−1, whereas the annual increasing trends in other basins ranged from 0.16 % year−1 to 0.39 % year−1. In the Yangtze and Mekong basins, ETa was more sensitive to vegetation greening, whereas climatic changes were the primary drivers of ETa tendencies in the other six basins in which the dominant driving factors were different, shifted from precipitation in the Mississippi, Murray-Darling and Nile basins to solar radiation in the Amazon basin. Specifically, precipitation and air temperature equivalently contributed to the ETa trend in the Lena Basin. The variations in ETa were strongly linked with El Niño events in the Amazon basin (energy-limited region) and Murray-Darling basin (water-limited region), reflecting the impacts of global climate extremes.
Cortical circuit function is regulated by extensively interconnected, diverse populations of GABAergic interneurons that may play key roles in shaping circuit operation according to behavioral ...context. A specialized population of interneurons that co-express vasoactive intestinal peptides (VIP-INs) are activated during arousal and innervate other INs and pyramidal neurons (PNs). Although state-dependent modulation of VIP-INs has been extensively studied, their role in regulating sensory processing is less well understood. We examined the impact of VIP-INs in the primary visual cortex of awake behaving mice. Loss of VIP-IN activity alters the behavioral state-dependent modulation of somatostatin-expressing INs (SST-INs) but not PNs. In contrast, reduced VIP-IN activity globally disrupts visual feature selectivity for stimulus size. Moreover, the impact of VIP-INs on perceptual behavior varies with context and is more acute for small than large visual cues. VIP-INs thus contribute to both state-dependent modulation of cortical activity and sensory context-dependent perceptual performance.
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•VIP interneurons regulate the state-dependent modulation of SST interneurons•VIP interneurons control visual feature selectivity in SST interneurons and excitatory neurons•The impact of VIP interneuron activity on visual perceptual performance varies with context
Ferguson et al. show that VIP interneurons regulate cortical visual feature selectivity. Loss of VIP interneurons decreases state-dependent modulation of SST interneurons and reduces visual tuning in SST interneurons and excitatory pyramidal neurons. Suppression of VIP interneurons has a size-dependent impact on perception of visual stimuli.
It is now recognized that G protein-coupled receptors (GPCRs), once considered largely independent functional units, have a far more diverse molecular architecture. Receptor activity-modifying ...proteins (RAMPs) provide an important example of proteins that interact with GPCRs to modify their function. RAMPs are able to act as pharmacological switches and chaperones, and they can regulate signaling and/or trafficking in a receptor-dependent manner. This review covers recent discoveries in the RAMP field and summarizes the known GPCR partners and functions of RAMPs. We also discuss the first peptide-bound structures of RAMP-GPCR complexes, which give insight into the molecular mechanisms that enable RAMPs to alter the pharmacology and signaling of GPCRs.
Second-line salvage therapy for patients with metastatic germ-cell cancer (GCC) after the first-line combination of VIP (etoposide, ifosfamide, cisplatin) therapy has not been established. This study ...evaluated the efficacy and tolerability of the TGP (paclitaxel, gemcitabine, cisplatin) combination chemotherapy as a second-line salvage therapy.
The medical records of 16 consecutive patients with metastatic GCC who had been treated with first-line VIP therapy followed by second-line TGP therapy between 2005 and 2019 were reviewed and statistically analyzed. Ten patients, excluding the 6 patients treated with TGP without unequivocal progression, were included in the efficacy analysis. All 16 patients were included in the safety analysis.
The median follow-up period from initial TGP administration was 78 months (interquartile range, 46-120 months). The estimated 5-year progression-free and overall survival rates for the 10 patients in the efficacy analysis were 70% and 100%, respectively. Grade 3/4 hematologic toxicity occurred in all 16 patients, but none developed uncontrollable infections or life-threatening bleeding. One patient died of treatment-related secondary leukemia, however.
The present study is to our knowledge the first to examine the therapeutic outcomes and safety profile of second-line TGP chemotherapy. VIP followed by TGP might be an alternative first- and second-line conventional regimen for patients with metastatic GCC in this granulocyte colony-stimulating factor era, especially for patients at a high risk of bleomycin-induced pulmonary toxicity.
VIP (etoposide, ifosfamide, cisplatin) is an alternative first-line therapy to BEP (bleomycin, etoposide, cisplatin) for patients with metastatic germ-cell cancer. Yet after first-line VIP has failed, there is no established second-line chemotherapeutic regimen for bleomycin-ineligible patients. For the patients, VIP followed by TGP (paclitaxel, gemcitabine, cisplatin) can serve as an alternative first- and second-line conventional regimen.
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