Release Sites Research Articles

Decreased Expression of the EAAT5 Glutamate Transporter at Photoreceptor Synapses in Early, Pre-Clinical Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis

Background: Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis. Methodology: In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites. Results: We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas. Conclusions: Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations.

Larval Transport Pathways for Lutjanus peru and Lutjanus argentiventris in the Northwestern Mexico and Tropical Eastern Pacific

Understanding how ocean currents influence larval dispersal and measuring its magnitude is critical for conservation and sustainable exploitation, especially in the Tropical Eastern Pacific (TEP), where the larval transport of rocky reef fish remains untested. For this reason, a lagrangian simulation model was implemented to estimate larval transport pathways in Northwestern Mexico and TEP. Particle trajectories were simulated with data from the Hybrid Ocean Coordinate Model, focusing on three simulation scenarios: (1) using the occurrence records of Lutjanus peru and L. argentiventris as release sites; (2) considering a continuous distribution along the study area, and (3) taking the reproduction seasonality into account in both species. It was found that the continuous distribution scenario largely explained the genetic structure previously found in both species (genetic brakes between central and southern Mexico and Central America), confirming that the ocean currents play a significant role as predictors of genetic differentiation and gene flow in Northwestern Mexico and the TEP. Due to the oceanography of the area, the southern localities supply larvae from the northern localities; therefore, disturbances in any southern localities could affect the surrounding areas and have impacts that spread beyond their political boundaries.

Wind effects on individual male and female Bactrocera jarvisi (Diptera: Tephritidae) tracked using harmonic radar.

Wind affects the movement of most volant insects. While the effects of wind on dispersal are relatively well understood at the population level, how wind influences the movement parameters of individual insects in the wild is less clear. Tephritid fruit flies, such as Bactrocera jarvisi, are major horticultural pests worldwide and while most tephritids are nondispersive when host plants are plentiful, records exist for potentially wind-assisted movements up to 200 km. In this study, harmonic radar (HR) was used to track the movements of both male and female lab-reared B. jarvisi in a papaya field. Overall flight directions were found to be correlated with wind direction, as were the subset of between-tree movements, while within-tree movements were not. Furthermore, the effect of wind direction on fly trajectories varied by step-distance but not strongly with wind speed. Mean path distance, step distance, flight direction, turning angle, and flight propensity did not vary by sex. Both male and female movements are well fit by 2-state hidden Markov models further supporting the observation that B. jarvisi move differently within (short steps with random direction) and between (longer more directional steps) trees. Data on flight directionality and step-distances determined in this study provide parameters for models that may help enhance current surveillance, control, and eradication methods, such as optimizing trap placements and pesticide applications, determining release sites for parasitoids, and setting quarantine boundaries after incursions.

Conserved autism-associated genes tune social feeding behavior in C. elegans

Animal foraging is an essential and evolutionarily conserved behavior that occurs in social and solitary contexts, but the underlying molecular pathways are not well defined. We discover that conserved autism-associated genes (NRXN1(nrx-1), NLGN3(nlg-1), GRIA1,2,3(glr-1), GRIA2(glr-2), and GLRA2,GABRA3(avr-15)) regulate aggregate feeding in C. elegans, a simple social behavior. NRX-1 functions in chemosensory neurons (ADL and ASH) independently of its postsynaptic partner NLG-1 to regulate social feeding. Glutamate from these neurons is also crucial for aggregate feeding, acting independently of NRX-1 and NLG-1. Compared to solitary counterparts, social animals show faster presynaptic release and more presynaptic release sites in ASH neurons, with only the latter requiring nrx-1. Disruption of these distinct signaling components additively converts behavior from social to solitary. Collectively, we find that aggregate feeding is tuned by conserved autism-associated genes through complementary synaptic mechanisms, revealing molecular principles driving social feeding.

A multi-instrument study of UV bursts and associated surges in AR 12957

The relationship between UV bursts and solar surges is complex, with these events sometimes being observed together and sometimes being observed independently. Why this sporadic association exists is unknown; however, it likely relates to the physical conditions at the site of the energy release that drives these events. Here, we aim to better understand the relationship between UV bursts and solar surges through a multi-instrument analysis of several associated events that occurred around the trailing sunspot in AR $12957$. We used data from Solar Orbiter, the Solar Dynamics Observatory (SDO), and the Interface Region Imaging Spectrograph (IRIS) to achieve our aims. These data were sampled on 3 March 2022 between $09$:$30$:$30$ UT and $11$:$00$:$00$ UT, during which time a coordinated observing campaign associated with the Slow Solar Wind Connection Solar Orbiter Observing Plan (SOOP) took place. Numerous small-scale negative polarity magnetic magnetic features (MMFs) were observed to move quickly (potentially up to $3.3$ km s$^ $) away from a sunspot until they collided with a more stable positive polarity plage region around $7$ Mm away. Several UV bursts were identified in IRIS slit-jaw imager (SJI) $1400$ data co-spatial to where these opposite polarity fields interacted, with spatial scales ($2$ Mm$<$) and lifetimes ($20<$ minutes) larger than typical values for such events. Two surges were also observed to occur at these locations, with one being short ($5$ Mm) and hot (bright in the IRIS SJI images), whilst the other was a cooler (dark in coronal imaging channels), longer surge that appeared to fill an active region loop. Magnetic reconnection between the negative polarity MMFs around the sunspot and the positive polarity plage region appears to be the driver of these events. Both the speed of the MMFs and the locally open magnetic topology of the plage region could possibly have been important for forming the surges.

Dopamine dynamics are dispensable for movement but promote reward responses.

Dopamine signalling modes differ in kinetics and spatial patterns of receptor activation1,2. How these modes contribute to motor function, motivation and learning has long been debated3-21. Here we show that action-potential-induced dopamine release is dispensable for movement initiation but supports reward-oriented behaviour. We generated mice with dopamine-neuron-specific knockout of the release site organizer protein RIM to disrupt action-potential-induced dopamine release. In these mice, rapid in vivo dopamine dynamics were strongly impaired, but baseline dopamine persisted and fully supported spontaneous movement. Conversely, reserpine-mediated dopamine depletion or blockade of dopamine receptors disrupted movement initiation. The dopamine precursor L-DOPA reversed reserpine-induced bradykinesia without restoring fast dopamine dynamics, a result that substantiated the conclusion that these dynamics are dispensable for movement initiation. In contrast to spontaneous movement, reward-oriented behaviour was impaired in dopamine-neuron-specific RIM knockout mice. In conditioned place preference and two-odour discrimination tasks, the mice effectively learned to distinguish the cues, which indicates that reward-based learning persists after RIM ablation. However, theperformance vigourwas reduced. During probabilistic cue-reward association, dopamine dynamics and conditioned responses assessed through anticipatory licking were disrupted. These results demonstrate that action-potential-induced dopamine release is dispensable for motor function and subsecond precision of movement initiation but promotes motivation and performance during reward-guided behaviours.

Insights into artificial waterhole utilization patterns by elephants and rhinos: Lessons from a South African Nature Reserve.

Artificial water provisioning is a common practice in southern African nature reserves, where different game species exhibit preferences for specific waterhole types. The movement patterns and behaviour of elephants and rhinos are closely linked to water availability, with these mega-herbivores noticeably influencing the environment and other species they interact with at waterholes. Since there is limited research on this topic, understanding preferences for different types of artificial waterholes is crucial, particularly during periods of water scarcity. This knowledge enables reserve managers to effectively manage the numbers and types of waterholes. In this study, we investigate artificial waterhole selection and preferences by elephants and rhinos in the Olifants West Nature Reserve, South Africa. The study area featured various waterhole types, including earth dams, concrete pans, reservoirs, and troughs. By employing camera traps, we analysed visitation frequency, timing of visits, and factors influencing visit frequency. Our findings revealed distinct preferences for specific waterhole types among different social groupings of the study species. Breeding herds of elephants predominantly utilized reservoirs and occasionally visited troughs, while bachelor herds favoured earth dams. Black rhinos showed a preference for earth dams, whereas white rhinos selected troughs and earth dams, with bachelor groups favouring troughs and female rhinos favouring earth dams. The outcomes of this study have significant implications for the development of comprehensive conservation plans in areas where these species reside, and for potential release sites.

Glyphosate impairs both structure and function of GABAergic synapses in hippocampal neurons

Glyphosate (Gly) is a broad-spectrum herbicide responsible for the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase known to be expressed exclusively in plants and not in animals. For decades Gly has been thought to be ineffective in mammals, including humans, until it was demonstrated that rodents treated with the Gly-based herbicide Roundup showed reduced content of neurotransmitters (e.g., serotonin, dopamine, norepinephrine, and acetylcholine), increased oxidative stress in the brain associated with anxiety and depression-like behaviors and learning and memory deficits. Despite compelling evidence pointing to a neurotoxic effect of Gly, an in-depth functional description of its effects on synaptic transmission is still lacking. To investigate the synaptic alterations dependent on Gly administration we performed whole-cell patch-clamp recordings and immunocytochemistry on mouse primary cultured hippocampal neurons. Our findings reveal that 30 min incubation of Gly at the acceptable daily intake dose severely impaired inhibitory GABAergic synapses. Further analysis pointed out that Gly decreased the number of postsynaptic GABAA receptors and reduced the amplitude of evoked inhibitory postsynaptic currents, the readily releasable pool size available for synchronous release and the quantal size. Finally, a decreased number of release sites has been observed. Consistently, morphological analyses showed that the density of both pre- and post-synaptic inhibitory compartments decorating pyramidal cell dendrites was reduced by Gly. In conclusion, our experiments define for the first time the effects induced by Gly on GABAergic synapses, and reveal that Gly significantly impairs both pre- and postsynaptic mechanisms.

LRRTM2 controls presynapse nano-organization and AMPA receptor sub-positioning through Neurexin-binding interface

Synapses are organized into nanocolumns that control synaptic transmission efficacy through precise alignment of postsynaptic neurotransmitter receptors and presynaptic release sites. Recent evidence show that Leucine-Rich Repeat Transmembrane protein LRRTM2, highly enriched and confined at synapses, interacts with Neurexins through its C-terminal cap, but the role of this binding interface has not been explored in synapse formation and function. Here, we develop a conditional knock-out mouse model (cKO) to address the molecular mechanisms of LRRTM2 regulation, and its role in synapse organization and function. We show that LRRTM2 cKO specifically impairs excitatory synapse formation and function in mice. Surface expression, synaptic clustering, and membrane dynamics of LRRTM2 are tightly controlled by selective motifs in the C-terminal domain. Conversely, the N-terminal domain controls presynapse nano-organization and postsynapse AMPAR sub-positioning and stabilization through the recently identified Neurexin-binding interface. Thus, we identify LRRTM2 as a central organizer of pre- and post- excitatory synapse nanostructure through interaction with presynaptic Neurexins.

Enhancing Thermochemical Energy Storage Performance of Perovskite with Sodium Ion Incorporation

Perovskite materials are promising for thermochemical energy storage due to their ability to undergo redox cycling over a wide temperature range. Although BaCoO3 exhibits excellent air cycling properties, its heat storage capacity in air remains suboptimal. This study introduces Na into the lattice structure to enhance oxygen vacancy formation and mobility. DFT+U simulations of the surface structure of Na-doped BaCoO3−δ indicate that incorporating Na improves surface stability and facilitates the formation of surface oxygen vacancies. NaxBa1−xCoO3−δ compounds were synthesized using a modified sol–gel method, and their properties were investigated. The experimental results demonstrate that Na doping significantly enhances the redox activity of the material. The heat storage capacity increased by above 50%, with the Na0.0625Ba0.9375CoO3−δ solid solution achieving a heat storage density of up to 341.7 kJ/kg. XPS analysis reveals that Na doping increases the concentration of surface defect oxygen, leading to more active oxygen release sites at high temperatures. This enhancement in redox activity aligns with DFT predictions. During high-temperature cycling, the distribution of Na within the material becomes more uniform, and no performance degradation is observed after 300 cycles. Even after 450 cycles, Na0.0625Ba0.9375CoO3−δ retains over 96% of its initial redox activity, significantly outperforming fresh BaCoO3−δ. These findings elucidate the mechanism by which Na doping enhances the thermochemical heat storage performance of BaCoO3−δ and provide new insights for the design of perovskite-based materials.

Biogenesis and reformation of synaptic vesicles.

Communication within the nervous system relies on the calcium-triggered release of neurotransmitter molecules by exocytosis of synaptic vesicles (SVs) at defined active zone release sites. While decades of research have provided detailed insight into the molecular machinery for SV fusion, much less is known about the mechanisms that form functional SVs during the development of synapses and that control local SV reformation following exocytosis in the mature nervous system. Here we review the current state of knowledge in the field, focusing on the pathways implicated in the formation and axonal transport of SV precursor organelles and the mechanisms involved in the local reformation of SVs within nerve terminals in mature neurons. We discuss open questions and outline perspectives for future research.

Developmental refinement of the active zone nanotopography and axon wiring at the somatosensory thalamus

Functional refinement of neural circuits is a crucial developmental process in the brain. However, how synaptic maturation and axon wiring proceed cooperatively to establish reliable signal transmission is unclear. Here, we combined nanotopography of release machinery at the active zone (AZ), nanobiophysics of neurotransmitter release, and single-neuron reconstruction of axon arbors of lemniscal fibers (LFs) in the developing mouse somatosensory thalamus. With development, the cluster of Cav2.1 enlarges and translocates closer to vesicle release sites inside the bouton, and LFs drastically shrink their arbors and form larger boutons on the perisomatic region of target neurons. Experimentally constrained simulations show that the nanotopography of mature synapses enables not only rapid vesicular release but also reliable transmission following repetitive firing. Sensory deprivation impairs the developmental shift of molecular nanotopography and axon wiring. Thus, we uncovered the cooperative nanotopographical and morphological mechanisms underlying the developmental establishment of reliable synaptic transmission.

Improving thermal shock and oxidation resistance of Cr3C2/WC-NiCr cermet coating by embedding large NiCrAlY superalloy particles

Cr3C2/WC-based cermet coating is widely used on the surface of mechanical equipment to strengthen its wear and corrosion resistance. Improving the high-temperature performance of cermet coating is the key to its industrial application. In this study, a novel type of bimodal microstructure cermet coating with the design of functional sites was fabricated via high-velocity air fuel (HVAF) spray technology. The toughness NiCrAlY superalloy particles are introduced into the traditional Cr3C2/WC-NiCr cermet structure to construct the thermal stress release site, which significantly improved the thermal shock resistance and thermal oxidation properties of the coating. The addition of NiCrAlY superalloy particle reduces the porosity of Cr3C2/WC-NiCr coating to 0.29 % and creates high-quality interface bonding and surface passivation layer. The newly structured cermet coating exhibits outstanding high-temperature performance. In a 1000 °C oxidation environment, the new coating remained intact after 120 h of exposure, while the traditional Cr3C2/WC-NiCr cermet coating exfoliated completely after 48 h of exposure. Further, in the thermal shock condition at 1000 °C, the lifetime of the new coating is 50 times greater than that of the traditional cermet coating, displaying excellent ability to relieve thermal stress. Additionally, the new coating shows good wear resistance and stability during high-temperature thermal exposure. After thermal exposure for 24 h and 72 h, the wear rates of the coating are 5.28 and 5.83 × 10−5 mm3 N−1 m−1, respectively, which is slightly lower than that of the as-sprayed coating. This study provides guidance for the improvement of high temperature resistance of thermally sprayed Cr3C2/WC-based cermet coatings.

In-situ construction of high-performance artificial solid electrolyte interface layer on anode surfaces for anode-free lithium metal batteries

The electrochemical performance of lithium metal batteries (LMBs) was hampered by the uncontrolled growth of lithium (Li) dendrites. To address this issue, the extensive application of artificial solid electrolyte interphase (SEI) coatings on anode surfaces emerged as an effective solution. Electrospinning, as an innovative technique for fabricating artificial SEI layers on the surface of copper (Cu) foil, effectively mitigated Li volume strain during cycling. In this study, an electrospun organic–inorganic composite nanofiber membrane was in-situ fabricated on Cu foil, serving as an artificial SEI layer (CuWs) for anode-free LMBs (AF-LMBs) to enhance battery performance. Lithiophilic polyvinylpyrrolidone was used as the polymer matrix, and Cu nitrate served as the inorganic functional particles capable of in-situ redox reactions. The CuWs with their three-dimensional (3D) network structure accommodated electrode volume changes and suppressed Li dendrite growth during Li deposition and stripping. Additionally, CuWs facilitated the in-situ generation of Li nitrate (LiNO3), which helped stabilize SEI layer and enhance Li utilization. The release sites of LiNO3 on the nanofibers enabled the in-situ reduction of metallic Cu, providing nucleation sites for Li deposition and forming the 3D ion–electron hybrid conductive networks. This CuWs layer reduced interfacial resistance and nucleation barriers, promoting uniform Li+ distribution on the anode surface. Li-Cu cells incorporating CuWs exhibited remarkable cycling stability, enduring over 460 cycles at 1.0 mA cm−2 and 1.0 mAh cm−2 with an average Coulombic efficiency of over 98.6 %. In Li-poor cells, the LFP|PE|CuWs achieved stable cycling for more than 30 cycles at 1.0 C, with a capacity retention rate of 92.0 %. These findings demonstrated that the CuWs membrane significantly enhanced the electrochemical performance of Li-poor cells and provided a novel artificial SEI protective strategy for advanced AF-LMBs with high energy density.

The Cost of Hatchery Straying: An Economic Case Study on Alaska Pink Salmon

Augmenting harvest using hatchery-produced salmon relies on fish returning to intended sites for capture. However, not all do – some stray, evading capture and entering wild spawning grounds, thus representing foregone yield. Here we ask, “what is the theoretical loss to harvesters as a result of straying?” We applied existing stray estimates and ex-vessel values from the world’s largest pink salmon hatchery-fishery program: Prince William Sound, Alaska, across three return years with full accounting of system wide harvest, escapement, and straying, to examine the value of strays under a range of scenarios that varied the component of the harvesting sector that might catch strays. In this system, approximately 1-5% of returning hatchery fish are estimated to stray away from release sites, which translates to approximate 0.8 - 4.5 million fish. We found that these strays were worth between $1 and $8 million per year, depending on the scenario and harvest year examined. While many important assumptions factor into this evaluation, our intention is for this work to spark dialogues about the economic tradeoffs associated with investing in stray reduction technologies, complementing the well-studied eco-evolutionary costs and benefits of straying.

Effects of release strategy, source population, and age on reintroduced scaled quail reproduction

AbstractTranslocation is one strategy to reestablish populations of scaled quail (Callipepla squamata). Initial reproductive success post‐translocation is important for establishing short‐lived species such as quail, but factors influencing reproductive success are poorly understood. We evaluated the effect of source population and variation in delayed release strategy (1−9 weeks) on nest initiation and nest survival of wild‐caught, translocated scaled quail. We trapped and translocated scaled quail in 2016–2017 from source populations in the Edwards Plateau and Rolling Plains ecoregions of Texas, USA, to a large contiguous (>40,000 ha) release site in Knox County, Texas. We used a multi‐state mark‐recapture model with state uncertainty to test for effects of release treatment, source population, age, release location, and year on nest initiation and survival. Increased length of holding time decreased re‐nesting effort. Yearlings were more likely to initiate nests than adults and the probability of re‐nesting was lower during the year with drought conditions. There was no effect of source population on any of the parameters we evaluated. Future scaled quail reintroduction efforts may benefit from prioritizing translocation of yearlings and conducting translocations when drought conditions are not forecasted.

Unraveling the Origins of an Extreme Solar Eruptive Event with Hard X-Ray Imaging Spectroscopy

Hard X-ray (HXR) observations are crucial for understanding the initiation and evolution of solar eruptive events, as they provide a key signature of flare-accelerated electrons and heated plasma. The potential of high-cadence HXR imaging for deciphering the erupting structure, however, has not received adequate attention in an era of extreme ultraviolet (EUV) imaging abundance. An extreme solar eruptive event on 2022 September 5 observed on the solar far side by both Parker Solar Probe and Solar Orbiter provides the opportunity to showcase the power of HXR imaging in the absence of high-cadence EUV imaging. We investigate the evolution of flare energy release through HXR timing, imaging, and spectral analyses using data from the Spectrometer/Telescope for Imaging X-rays (STIX) on board Solar Orbiter. STIX provides the highest cadence imaging of the energy release sites for this far-side event and offers crucial insight into the nature of energy release, timing of flare particle acceleration, and evolution of the acceleration efficiency. We find that this is a two-phase eruptive event, rather than two distinct eruptions, as has been previously suggested. The eruption begins with an initial peak in flare emission on one side of the active region (AR), marking the rise/destabilization of a loop system followed by notable episodes of energy release across the AR and an eruptive phase associated with a very fast coronal mass ejection, type III radio bursts, and solar energetic particles. We demonstrate that high-cadence HXR imaging spectroscopy is indispensable for understanding the formation of powerful, space-weather relevant eruptions.

Bunyamwera Virus Infection of Wolbachia-Carrying Aedes aegypti Mosquitoes Reduces Wolbachia Density.

Wolbachia symbionts introduced into Aedes mosquitoes provide a highly effective dengue virus transmission control strategy, increasingly utilised in many countries in an attempt to reduce disease burden. Whilst highly effective against dengue and other positive-sense RNA viruses, it remains unclear how effective Wolbachia is against negative-sense RNA viruses. Therefore, the effect of Wolbachia on Bunyamwera virus (BUNV) infection in Aedes aegypti was investigated using wMel and wAlbB, two strains currently used in Wolbachia releases for dengue control, as well as wAu, a strain that typically persists at a high density and is an extremely efficient blocker of positive-sense viruses. Wolbachia was found to reduce BUNV infection in vitro but not in vivo. Instead, BUNV caused significant impacts on density of all three Wolbachia strains following infection of Ae. aegypti mosquitoes. The ability of Wolbachia to successfully persist within the mosquito and block virus transmission is partially dependent on its intracellular density. However, reduction in Wolbachia density was not observed in offspring of infected mothers. This could be due in part to a lack of transovarial transmission of BUNV observed. The results highlight the importance of understanding the complex interactions between multiple arboviruses, mosquitoes and Wolbachia in natural environments, the impact this can have on maintaining protection against diseases, and the necessity for monitoring Wolbachia prevalence at release sites.

Free Flight Training as a Tool for Psittacine Reintroductions

As habitat loss and other threats accelerate, ecological restoration and reintroduction science are becoming progressively more important. The psittacines are among the most endangered bird groups and are prime candidates for restoration through reintroduction. Unfortunately, post-release survival of captive-raised animals is often quite low because, in part, of high predation rates, low site fidelity, poor flight ability, and low flock cohesion. Current best practices in parrot release hold the birds in captivity for a year or more and include distinct methods to address each of these challenges. Here, we conduct a small-scale, proof-of-concept study using free flight methods and human-socialized trained adult birds to hand raise and release a group of six fledgling Blue-and-yellow Macaws in their historical range in southeastern Brazil. All six released birds showed strong flock cohesion and fidelity to the release site, avoided predation, and survived without supplemental feeding for over one year. One bird was captured by local people but was recovered and rereleased and it has reintegrated into the group and is still alive and doing well. The human-socialized trained adult birds modeled both desirable behaviors (flocking, foraging, reacting to predators) and undesirable behaviors and they were returned to captivity before the conclusion of this study. Our study suggests that free flight training has great potential to help captive-raised young attain a broad array of vital skills needed for survival post-release.

Insights into the Synaptic Properties of Dopamine Release Revealed by Single Walled Carbon Nanotube Biosensors

It is thought that there are two distinct modes of chemical neurotransmission, referred to as fast (synaptic) transmission and slow (volume) transmission. Fast transmission, mediated by ligand-gated ionotropic receptors, operate with millisecond temporal and nanometer spatial precision in excitatory and inhibitory synapses, primarily mediated by glutamate and GABA, respectively. In contrast, slow transmission relies on activation of G-protein coupled receptors (GPCRs) and is mediated by several classes of neuromodulators, including dopamine. Neuromodulators are thought to operate at temporal scales that range from hundreds of milliseconds to minutes, with a spatial specificity that is insufficiently understood but generally described as “diffuse”. In this work, we provide new evidence that shows the spatial precision of dopamine transmission is highly reminiscent of the spatial properties of signaling mediated by the fast acting neurotransmitters.To gain this insight, we used an optical assay named “DopaFilm” that is based on oligonucleotide functionalized single walled carbon nanotube dopamine sensors (nanosensors). Primary dopaminergic neurons were grown on top of glass coverslips functionalized with nanosensors, which enabled visualization of dopamine exocytosis events in single release sites under a continuous 785nm excitation laser. In axonal arbors, DopaFilm can report evoked and spontaneous dopamine release events with high signal to noise ratios of up to 50. Recording on DopaFilm revealed dopamine release is fast, calcium-dependent, and reliant on similar presynaptic protein machinery employed by fast neurotransmitters. These findings challenge the notion that dopamine is a slow transmitter; however it doesn’t preclude the possibility of imprecise spatial signaling, consistent with volume transmission theory. More recent data from our lab now challenges the spatial characteristics of volume transmission model as currently understood in the literature. In this talk, I will discuss new insights gained on dopamine signaling including clear examples of precise spatial arrangements of dopamine release sites, and ultrastructural, biochemical and spatial transcriptomic data that shows that neuromodulatory action can be highly spatially precise in nature.