Release Sites Research Articles

Piscivorous brown trout Salmo trutta does not migrate from distant downstream habitats to a massive release site for chum salmon Oncorhynchus keta fry in the Chitose River, northern Japan

Piscivorous brown trout Salmo trutta does not migrate from distant downstream habitats to a massive release site for chum salmon Oncorhynchus keta fry in the Chitose River, northern Japan

Highly Prolonged Release of the Cancer Vaccine and Immunomodulator via a Two-Layer Biodegradable Microneedle for Prophylactic Treatment of Metastatic Cancer.

Simultaneous sustained release of cancer vaccines and immunomodulators may effectively trigger durable immune responses and avoid multiple administrations. Here, we established a biodegradable microneedle (bMN) based on a biodegradable copolymer matrix made of polyethylene glycol (PEG) and poly(sulfamethazine ester urethane) (PSMEU). This bMN was applied to the skin and slowly degraded in the epidermis/dermis layers. Then, the complexes composed of a positively charged polymer (DA3), cancer DNA vaccine (pOVA), and toll-like receptor 3 agonist poly(I/C) were synchronously released from the matrix in a pain-free manner. The whole microneedle patch was fabricated with two layers. The basal layer was formed using polyvinyl pyrrolidone/polyvinyl alcohol that could be rapidly dissolved upon applying the microneedle patch to the skin, whereas the microneedle layer was formed by complexes encapsulating biodegradable PEG-PSMEU, which was stuck at the injection site for sustained release of therapeutic agents. According to the results, 10 days is the time for the complexes to be completely released and express specific antigens in antigen-presenting cells in vitro and in vivo. It is noteworthy that this system could successfully elicit cancer-specific humoral immune responses and inhibit metastatic tumors in the lungs after a single shot of immunization.

Orang-utans’ (<i>Pongo pygmaeus wurmbii</i>) Activity Pattern in Camp Release and Feeding Site of Lamandau Wildlife Sanctuary, Central Borneo, Indonesia

The Bornean orang-utan (Pongo pygmaeus wurmbii) release process at Lamandau Wildlife Reserve applies the soft-release method. In this method, there is still provisioning additional food on the feeding site by human. The existence of camp release and feeding sites in the vicinity of release forests is assumed to have an impact on orang-utans’ activity patterns. This assumption is related to the principle of releasing them into their natural forest habitat, namely by reducing direct interaction between humans and orang-utans. The aims of this research were: (i) to measure the intensities of orang-utan presence on camp and feeding site, (ii) to analyze the correlation between phenology and orang-utan’s presence on camp and feeding site, and (iii) to assess orang-utan’s activity budgets, diet composition, and vertical used on camp, feeding site, and forest. Activity budgets of five group orang-utans with different categories based on age and sex were compared using the focal animal sampling method and instantaneous records. The analysis showed no correlation between the intensities of orang-utan presence and phenology. However, there were significant differences in activity patterns between adult and adolescent orang-utans. The findings revealed that adult orang-utans activity pattern tended to be high in resting at all observation locations while adolescents spending more their activity for feeding. Orang-utans at 0-10 m of height classes tend to do more activity. Almost all orang-utans feed on a non-forest diet (45-67%) in the camp release, feeding site, and surrounding. We assumed that the existence of a camp release and feeding site near the release point are affecting factors in a successful reintroduction of ex-rehabilitate orang-utans.

“Sport creates value” Sport activities as part of a meaningful life?

Sport has often been viewed as a valuable part of our individual and collective lives because of its potential to bring physical and mental health benefits and to help build communities. In addition to providing a site for stress release and having a good time, sport can also be a context where people explore existential questions and what it means to live a ‘meaningful’ and ‘good’ life. In this presentation, I will discuss how people in contemporary societies engage with their life-construction and how involvement in sport and physical activity might contribute, for some, in answering deeper questions concerning how to live well. I draw on empirical studies and philosophical work to explore how different forms of sport provide opportunities for experiencing meaningfulness, and whether new forms of physical cultures reflect changing meanings by which people live their lives. Finally, I will question whether sport can bring ‘too much’ meaning to some people’s lives and whether we can be mistaken about the meaningfulness of our sporting activities.

Comparing dominance relationships and movement of native marble trout (Salmo marmoratus) and introduced rainbow trout (Oncorhynchus mykiss).

Behaviour observations of the endangered native marble trout (Salmo marmoratus, Cuvier, 1829) and introduced rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) in the laboratory and in a tributary to the Idrijca River in Slovenia were combined to study the movements and dominance relationships between individuals of the two species in an open field test. Under laboratory conditions, no difference between the species was detected for neither time spent actively or distance moved. In species paired tests, rainbow trout initiated more aggressive behaviours towards marble trout than vice versa, and rainbow trout were clearly the dominant individuals. After simultaneous release in the river, marble trout immediately left the release area and spent twice as long time as rainbow trout until they settled in an area of the river; therefore, the release site was immediately occupied exclusively by rainbow trout. Thus, the dominant and aggressive behaviour of rainbow trout seen in the laboratory before release might have influenced marble trout's subsequent behaviour in the river, by marble trout leaving the areas occupied by rainbow trout and moving to locations further away from the release site. In the field, the marble trout occupied sites individually, whereas rainbow aggregated at a few locations. Rainbow trout showed higher movement activity in the morning compared to marble trout. There was a positive correlation between swimming speed in the laboratory and movement in the field for marble trout but not for rainbow trout. In conclusion, the results in this study support the need to end stocking of rainbow trout in rivers with native marble trout. To better understand the interaction between the species, and to develop efficient management plans to protect the native marble trout, reference behaviours should first be understood, and future research in sites where the two species do not co-exist is needed. This is especially important for marble trout for which behavioural research and data are lacking.

Northern bobwhite subspecies exhibit reduced survival and reproduction when translocated outside their native range

AbstractThe popularity of translocation as a conservation tool to reintroduce and re‐stock existing populations of northern bobwhite (Colinus virginianus) to restored habitat has increased following decades‐long decline; however, population sources are limited to a few areas in the United States where stable or increasing populations remain. Understanding how demographic parameters of translocated individuals vary by source region and subspecies will help increase the effectiveness of translocation as a recovery tool. Our objectives were to compare survival, movements, and reproduction of 2 translocated subspecies of bobwhite. We translocated 665 bobwhites (n = 253 northwest Texas [C. v. taylori];n = 412 south Texas [C. v. texanus]) to an 890‐ha site in northcentral Texas, USA, during March 2019–2021 and radio‐marked 380 (n = 184 northwest Texas;n = 196 south Texas). The northwest subspecies is considered the subspecies native to the release site. Radio‐marked bobwhites from south Texas were 1.25 times (95% CI = 0.98–1.60) more likely to die on the study site than individuals from northwest Texas. Home ranges (95% kernel density estimator) were larger for bobwhites sourced from northwest Texas (51 ha, 95% CI = 39–63 ha) compared to individuals from south Texas (32 ha, 95% CI = 22–42 ha). Individuals from northwest Texas were 1.5 times (95% CI = 1.10–1.80) more likely to leave the study site but 3.2 times (95% CI = 2.32–4.19) more likely to return to the study site after dispersing. Radio‐marked bobwhites from northwest Texas produced 44% more nests per female than birds from south Texas. Managers who wish to use non‐native subspecies of bobwhite to supplement a translocation effort should be cognizant of the potential reductions in survival and reproduction that may occur.

Supramolecular organization of the postsynaptic density for trans-synaptic alignment in excitatory synapse observed by cryo-electron tomography.

Nanoscale organization of proteins within synapses are critical for maintaining and regulating synaptic transmission and plasticity. Revealing the supramolecular structure of synapses will lead to better understanding of synaptic functions in the brain, which feeds through to new therapeutic strategies and clinical trials. In this study, we used cryo-electron tomography to directly visualize in situ three-dimensional architecture and supramolecular organization of trans-synaptic nanocolumns in their native cellular context. Our findings strongly suggested a standard trans-synaptic nanocolumn contains a synaptic vesicle at release site, a cluster of postsynaptic receptors and a PSD nanodomain, together creating a physical transcellular alignment. Quantitative analyses revealed PSD nanodomain is the basic unit and form different sizes of PSD clusters. Furthermore, high-resolution tomograms obtained from the synaptosome sample allows us to detect the glutamate receptor-like particles and putative adhesion molecules. These results clarify unresolved issues regarding the ultrastructural features of synapses and support the idea that trans-synaptic alignment exists to carry out synaptic functions. The supramolecular architecture of the basic PSD nanodomain and its clusters suggests a higher-order organization of trans-synaptic nanocolumn of central nervous system synapses to maintain and regulate synaptic transmission.

Local PI(4,5)P2 signaling inhibits fusion pore expansion during exocytosis.

Phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) is an important signaling phospholipid that is required for regulated exocytosis and some forms of endocytosis. The two processes share a topologically similar pore structure that connects the vesicle lumen with the outside. Widening of the fusion pore during exocytosis leads to cargo release, while its closure initiates kiss&run or cavicapture endocytosis. We show here, using live-cell total internal reflection fluorescence (TIRF) microscopy of insulin granule exocytosis, that transient accumulation of PI(4,5)P2 at the release site recruits components of the endocytic fission machinery and stalls the late fusion pore expansion that is required for peptide release. The absence of clathrin differentiates this mechanism from clathrin-mediated endocytosis. Knockdown of phosphatidylinositol-phosphate-5-kinase-1c or optogenetic recruitment of 5-phosphatase reduces PI(4,5)P2 transients and accelerates fusion pore expansion, suggesting that acute PI(4,5)P2 synthesis is involved. Thus, local phospholipid signaling inhibits fusion pore expansion and peptide release through an unconventional endocytic mechanism.

Stress brings out the best: Potassium transport by KdpFABC.

The kdp operon is used by bacteria to combat osmotic stress, such as the loss of K+ in the media or exposure to fresh water in the environment. Like all organisms across the kingdoms of life, elevated K+ in the cytosol is essential for maintaining the membrane potential, driving a variety of transport processes, and in bacteria, for maintenance of pH, cell growth and division. KdpD and KdpE comprise a constitutively expressed two-component system for detecting osmotic stress and inducing the expression of the K+ transport system KdpFABC. This system represents an unusual partnership between a K+ channel (KdpA) and a P-type ATPase (KdpB). Recent work has produced a series of structures in a variety of different states corresponding to major intermediates in the Post-Albers transport cycle that is characteristic of the P-type ATPase superfamily. Based on this work, a detailed reaction mechanism has been proposed in which KdpA selects K+ from the periplasm, a unique intramembrane tunnel delivers the K+ to canonical ion binding sites in KdpB where ATP-driven conformational changes deliver the ion to the cytosol. This mechanism highlights fascinating evolutionary adaptations of a K+ channel, which appears to be static and no longer provides a conduit across the membrane, and a P-type ATPase, which does not directly bind ions from the periplasm and may not have innate ion selectivity. Despite tremendous progress in characterizing this system, questions persist about the nature of the intramembrane tunnel, the release site of K+ from KdpB and the energetics of the transport process.

Syngap LLPS condensates as the basic platform for recruiting PSD95 and receptor oligomers for generating neuronal excitatory synapses.

The neuronal post-synaptic structure consists of nano-scale domains that need to be precisely apposed to the pre-synaptic neurotransmitter release sites. This exquisite assembly of post-synaptic receptors and scaffold proteins is essential for proper synaptic function. However, the biophysical mechanisms that retain receptors and scaffold proteins at the post-synapse are not well understood. Specifically, a mechanism that can induce clusters of PSD95, a key scaffold protein, at low concentrations, such as those expected before the formation of functional post-synapses, and which can induce long-term retention of post-synaptic receptors, remains to be hardly known.

Identifying the energy release site in a solar microflare with a jet

Context. One of the main science questions of the Solar Orbiter and Parker Solar Probe missions deals with understanding how electrons in the lower solar corona are accelerated and how they subsequently access interplanetary space. Aims. We aim to investigate the electron acceleration and energy release sites as well as the manner in which accelerated electrons access the interplanetary space in the case of the SOL2021-02-18T18:05 event, a GOES A8 class microflare associated with a coronal jet. Methods. This study takes advantage of three different vantage points, Solar Orbiter, STEREO-A, and Earth, with observations drawn from eight different instruments, ranging from radio to X-ray. Multi-wavelength timing analysis combined with UV/EUV imagery and X-ray spectroscopy by Solar Orbiter/STIX (Spectrometer/Telescope for Imaging X-rays) is used to investigate the origin of the observed emission during different flare phases. Results. The event under investigation satisfies the classical picture of the onset time of the acceleration of electrons coinciding with the jet and the radio type III bursts. This microflare features prominent hard X-ray (HXR) nonthermal emission down to at least 10 keV and a spectrum that is much harder than usual for a microflare with γ = 2.9 ± 0.3. From Earth’s vantage point, the microflare is seen near the limb, revealing the coronal energy release site above the flare loop in EUV, which, from STIX spectroscopic analysis, turns out to be hot (i.e., at roughly the same temperature of the flare). Moreover, this region is moving toward higher altitudes over time (∼30 km s−1). During the flare, the same region spatially coincides with the origin of the coronal jet. Three-dimensional (3D) stereoscopic reconstructions of the propagating jet highlight that the ejected plasma moves along a curved trajectory. Conclusions. Within the framework of the interchange reconnection model, we conclude that the energy release site observed above-the-loop corresponds to the electron acceleration site, corroborating that interchange reconnection is a viable candidate for particle acceleration in the low corona on field lines open to interplanetary space.

Day-Time Roost Patterns of New and Previously Translocated North Island Brown Kiwi (Apteryx mantelli)

Information on the day-time roost areas of North Island brown kiwi (NIBK) (Apteryx mantelli), particularly post-translocation, is limited. This study aimed to determine the day-time roost areas of newly translocated NIBK and compare these with birds that had established from a translocation in the previous year. Radio telemetry was used to monitor sub-adult NIBK in the first three weeks post-translocation simultaneously with birds released in the previous year. The data from 15 birds (nine translocated in 2014 and six translocated in 2013) were used to calculate the area over which roost sites were distributed. Areas were estimated using Minimum Convex Polygon (MCP, Ha) and 50 percentile kernel density estimation (KDE, Ha). No significant difference in MCP was determined between newly translocated 2014 birds (21.3 Ha, SE 7.92) and those translocated in 2013 (22.85 Ha, SE 10.84) or between KDE50 for 2013 birds (16.30 Ha, SE 7.44) compared with 2014 birds (20.66 Ha, SE 8.29). Within the first three weeks post-translocation, most of the 2014 birds remained within the vicinity of their release site, which may be due to a combination of suitable habitat/roost sites and the ‘anchoring’ effect of previously established 2013 birds. This study provides new information on roost areas of newly translocated NIBK and highlights the importance of post-translocation monitoring.

DEVELOPMENT OF A NOVEL DRUG DELIVERY SYSTEM (DDS) TO DELIVER DRUGS DIRECTLY TO THE COLONIC MUCOSA TO IMPROVE EFFICACY AND REDUCE SYSTEMIC EXPOSURE FOR THE TREATMENT OF ULCERATIVE COLITIS (UC)

Abstract The clinical remission rate in moderate to severe ulcerative colitis (UC) and Crohn’s Disease (CD) has plateaued at ~15-20% despite the approval of multiple therapeutics. Research has shown that an inadequate amount of drug at the disease site in the colon may be responsible for limited clinical benefit. The Drug Delivery System (DDS) is an ingestible electronic targeted delivery device containing a localization system to autonomously identify colon entry based on gastrointestinal (GI) anatomy, independent of the variable GI physiological conditions deliver a bolus dose of a liquid drug formulation to the colon mucosa to improve efficacy and reduce systemic toxicity. Here, we aim to evaluate the safety, tolerability, and functionality of a single dose of the DDS using gamma scintigraphy images as a reference in both normal healthy volunteers (NHV) (PM-601) and subjects with active UC (PM-602) in a fasted state. A total of twelve NHV (N=12) and seven subjects with an endoscopically confirmed history of UC and active UC (N=7) status, defined as having a Mayo score ≥ 2 or elevated fecal calprotectin protein or high sensitivity C-reactive protein within one month of the screening visit, were enrolled and dosed in these studies. Each subject fasted overnight and was dosed with a single DDS device before resuming a normal diet at 4 hours post-dose. Each device was filled with radioactive marker indium-111 DTPA and co-administered with water to which technetium-99m DTPA was added to monitor device GI transit and payload release in the GI tract. The GI transit of the device and delivery location of the radioactive payload were confirmed by serial scintigraphy imaging and compared with the localization data recovered from the devices. GI transit metrics showed a more variable GI motility and frequent bowel movements were observed among active UC subjects compared to NHV (Table 1). The DDS device was well tolerated in both NHV and active UC subjects. One subject with active UC (PM-602) experienced mild intermittent abdominal cramping following device administration possibly related to the device, which resolved on the same day. No other device-related AEs were reported in these studies. The results from these two studies demonstrated a total of 17 out of 19 DDS devices (90%) successfully identified colon entry and 15 out of 19 DDS devices (79%) delivered the radio payload into the colon regardless of variable GI transit time, the level of inflammation, or the presence of blood in the stool (Table 1 & 2). The dispersion of the radiotracer adequately covered the colon from the site of release throughout the remainder of the colon. These results demonstrated that the DDS device was well-tolerated and functioned as intended to deliver radiotracer throughout the colon regardless of variable GI motility, disease, and inflammation status.

Computational Model of Noradrenaline Modulation of Astrocyte Responses to Synaptic Activity

The mathematical modeling of synaptically connected neuronal networks is an established instrument for gaining insights into dynamics of neuronal ensembles and information processing in the nervous system. Recently, calcium signaling in astrocytes—glial cells controlling local tissue metabolism and synapse homeostasis—and its corresponding downstream effect on synaptic plasticity and neuromodulation appeared in the limelight of modeling studies. Here, we used mechanism-based mathematical modeling to disentangle signaling pathways and feedback loops in the astrocytic calcium response to noradrenaline, an important neuromodulator marking periods of heightened alertness and arousal. The proposed model is based on an experiment-based 2D representation of astrocyte morphology, discrete random glutamate synapses with placement probability defined by the morphology pattern, and spatially heterogeneous noradrenaline sources, reflecting axonal varicosities of the adrenergic axons. Both glutamate and noradrenaline drive Ca2+ dynamics in the astrocyte in an additive or synergistic manner. Our simulations replicate the global activation of astrocytes by noradrenaline and predict the generation of high-frequency Ca2+ waves in a dose-dependent manner and the preferred Ca2+ wave origination near noradrenaline release sites if they colocalise with high-density clusters of glutamate synapses. We tested positive feedback loops between noradrenaline release and glutamate spillover directly or mediated by gliotransmitter release from the activated astrocyte. The simulations suggest that the coupled stochastic drive by glutamate and noradrenaline release converges on the graded modulation of the IP3 level, which is translated into whole-cell Ca2+ waves of different frequencies. Thus, the proposed approach is supported by experimental data and can be used to address situations inaccessible directly by experiment, and is a starting point for a more detailed model that includes other signaling mechanisms providing negative feedback.

Understanding movement and habitat‐use to guide reintroductions and habitat rehabilitation for a nonmigratory freshwater fish

Outcomes from restoration and reintroduction programs can be enhanced by understanding the habitat use of animals, and how likely they are to move and why? River blackfish are native to southeastern Australia where their range and abundance have declined. We reintroduced 27 river blackfish into two sites, one where rehabilitation had been undertaken (with more vegetation, instream woody habitat, and undercut banks) and an unmanipulated control site. We monitored fish for 9 months after release to assess site occupancy, habitat use, and drivers of movement. We modeled the likelihood of fish remaining at either site, their habitat use, and predictors of movement (site type, habitat, time, and river discharge). While more fish remained at the treatment site, this difference was not statistically significant. Future trials incorporating increased numbers of fish and replicate treatment and control release sites would allow a more detailed test of whether fish are more likely to remain at restored sites. Fish spent more time in deeper areas with more riparian vegetation. Habitat, flow, and time since release were significant predictors of fish movement, with fish more likely to move from release sites with less suitable habitat, during rainfall events, and during the initial stages of our study. Our results illustrate that blackfish are a suitable candidate for translocations, retaining their largely sedentary behavior and should be easily measurable if restoration has provided suitable habitat and their presence is an indicator of success. Our work is also a useful case study for translocation of other nonmigratory fish worldwide.

Neurexins in serotonergic neurons regulate neuronal survival, serotonin transmission, and complex mouse behaviors.

Extensive serotonin (5-hydroxytryptamine, 5-HT) innervation throughout the brain corroborates 5-HT's modulatory role in numerous cognitive activities. Volume transmission is the major mode for 5-HT transmission but mechanisms underlying 5-HT signaling are still largely unknown. Abnormal brain 5-HT levels and function have been implicated in autism spectrum disorder (ASD). Neurexin (Nrxn) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in Nrxn genes are associated with neurodevelopmental disorders including ASD. However, the role of Nrxn genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three Nrxn genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of Nrxns in 5-HT neurons reduced the number of serotonin neurons in the early postnatal stage, impaired 5-HT release, and decreased 5-HT release sites and serotonin transporter expression. Furthermore, 5-HT neuron-specific Nrxn knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission, 5-HT neuron survival, and the execution of complex behaviors.

The efficacy of translocation as a tool to augment populations of Gambel's quail

AbstractTranslocation is a management strategy that can be used to augment and reestablish populations or increase a species' range by establishing new populations. Gambel's quail (Callipepla gambelii) are the only native upland game birds in many desert areas of the American Southwest. Drought may be a driver in Gambel's quail population declines; however, quail in urban environments may remain abundant because these areas may contain more reliable sources of food, water, and cover. We hypothesized that translocation of urban quail following a wet winter, when resources are plentiful in their native habitat, might allow us to increase the rate at which extant populations are able to recover following drought by capitalizing on the high reproductive capacity of quail. To assess translocation as a management tool for augmentation of populations of Gambel's quail, we translocated 370 quail from 2019 to 2021 to augment 2 sites in the Altar Valley in Arizona, USA: King's Anvil Ranch (KA) and Santa Margarita Ranch (SM). We radiotracked 155 female quail on 2 study areas (KA: n = 77, SM: n = 78) to estimate 200‐day post‐release survival. Release site had the most impact on demographic rates. Quail in KA had higher survival (63.4–70.9%) than quail in SM (19.3–33.1%); however, quail in SM had higher nesting effort and success (nest effort = 63%, nest success = 50%) than quail in KA (nest effort = 33%, nest success: 0%) in the first year. Although this study showed that urban quail can survive and reproduce following translocation, neither site showed both high survival and high reproductive success. Furthermore, although spring call counts indicated augmentation may have had some short‐term benefits due to increased reproductive activity, we are not able to conclude that it increased quail abundance. Given the low annual adult survival rates of Gambel's quail, high spring‐summer survival alone will not be enough to boost wild populations in a measurable way the following year. Therefore, the ability of translocation to augment extant populations may be limited by low and variable reproductive success.

Noradrenaline released from locus coeruleus axons contracts cerebral capillary pericytes via α2 adrenergic receptors

Noradrenaline (NA) release from locus coeruleus axons generates vascular contractile tone in arteriolar smooth muscle and contractile capillary pericytes. This tone allows neuronal activity to evoke vasodilation that increases local cerebral blood flow (CBF). Much of the vascular resistance within the brain is located in capillaries and locus coeruleus axons have NA release sites closer to pericytes than to arterioles. In acute brain slices, NA contracted pericytes but did not raise the pericyte cytoplasmic Ca2+ concentration, while the α1 agonist phenylephrine did not evoke contraction. Blocking α2 adrenergic receptors (α2Rs, which induce contraction by inhibiting cAMP production), greatly reduced the NA-evoked pericyte contraction, whereas stimulating α2Rs using xylazine (a sedative) or clonidine (an anti-hypertensive drug) evoked pericyte contraction. Noradrenaline-evoked pericyte contraction and capillary constriction are thus mediated via α2Rs. Consequently, α2Rs may not only modulate CBF in health and pathological conditions, but also contribute to CBF changes evoked by α2R ligands administered in research, veterinary and clinical settings.

Long-term methamphetamine self-administration increases mesolimbic mitochondrial oxygen consumption and decreases striatal glutathione

Neurotoxic regimens of methamphetamine (METH) are known to increase reactive oxygen species (ROS), affect redox homeostasis, and lead to damage in dopamine neurons. Functional changes induced by long-term METH self-administration on mitochondrial respiratory metabolism and redox homeostasis are less known. To fill this gap, we implanted a jugular catheter into adult male mice and trained them to nose poke for METH infusions. After several weeks of METH exposure, we collected samples of the ventral striatum (vST) and the ventral midbrain (vMB). We used HPLC to determine the levels of the ROS scavenger glutathione in its reduced (GSH) and oxidized forms. Then, we used high-resolution respirometry to determine the oxygen consumption rate (OCR) of mitochondrial complexes. Finally, using in vivo electrophysiology, we assessed changes in dopamine neuron firing activity in the VTA. METH self-administration produced a decrease of the GSH pool in vST, correlating with lifetime METH intake. We observed increased mitochondrial respiration across the two mesolimbic regions. METH self-administration decreases firing rate and burst activity but increases the number of spontaneously active dopamine neurons per track. We conclude that METH self-administration progressively decreased the antioxidant pool in sites of higher dopamine release and produced an increase in mitochondrial metabolism in the mesolimbic areas, probably derived from the increased number of dopamine neurons actively firing. However, dopamine neuron firing activity is decreased by METH self-administration, reflecting a new basal level of dopamine neurotransmission.

Plant clustering generates negative plant–soil feedback without changing the spatial distribution of soil fauna

Abstract. The spatial distribution of resources affects ecological processes at all levels of biological organization. However, it remains to be tested how the spatial configuration of belowground resources affects the community dynamics of soil organisms and resulting plant–soil feedbacks. We used Agrostis stolonifera plants in different spatial configurations in mesocosms to study the dispersal patterns of soil nematodes and rotifers. Plant–soil feedbacks were later assessed by re-sowing the mesocosms with Lolium perenne and Plantago lanceolata after removing all the initial A. stolonifera plants from the mesocosms. Bacterial-feeding nematodes and rotifers spread fast, whereas plant-feeding nematodes barely dispersed from the release sites. These spread patterns of nematodes and rotifers depended on the life-history traits and not on the spatial pattern of the plants. However, more clustered plants developed a higher total biomass and caused a reduced growth of the subsequent vegetation. Our results demonstrate that the mere spatial pattern of a single plant species can alter the strength of plant–soil feedbacks. This has important implications for understanding the impact of planting or replanting schemes and other changes in the spatial configuration of plants on long-term vegetation development and succession.