We like neurons.

Charleese Williams is the winner of the 2021 Rising Black Scientists Award for an undergraduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.

Science as a tool for justice.

Elle Lett is the winner of the 2021 Rising Black Scientists Award for a post-graduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.

Phase precession in the human hippocampus and entorhinal cortex.

Knowing where we are, where we have been, and where we are going is critical to many behaviors, including navigation and memory. One potential neuronal mechanism underlying this ability is phase precession, in which spatially tuned neurons represent sequences of positions by activating at progressively earlier phases of local network theta oscillations. Based on studies in rodents, researchers have hypothesized that phase precession may be a general neural pattern for representing sequential events for learning and memory. By recording human single-neuron activity during spatial navigation, we show that spatially tuned neurons in the human hippocampus and entorhinal cortex exhibit phase precession. Furthermore, beyond the neural representation of locations, we show evidence for phase precession related to specific goal states. Our findings thus extend theta phase precession to humans and suggest that this phenomenon has a broad functional role for the neural representation of both spatial and non-spatial information.

Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level.

Goal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish. We find global, recurring dynamics of brain states to exhibit pre-motor bifurcations toward mutually exclusive decision outcomes. These dynamics arise from a distributed network displaying trial-by-trial functional connectivity changes, especially between cerebellum and habenula, which correlate with decision outcome. Within this network the cerebellum shows particularly strong and predictive pre-motor activity (>10 s before movement initiation), mainly within the granule cells. Turn directions are determined by the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the rate of bi-hemispheric population ramping quantitatively predicts decision time on the trial-by-trial level. Our results highlight a cognitive role of the cerebellum and its importance in motor planning.

Cortical-subcortical interactions in goal-directed behavior.

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.

Converting an allocentric goal into an egocentric steering signal.

Neuronal signals that are relevant for spatial navigation have been described in many species1-10. However, a circuit-level understanding of how such signals interact to guide navigational behaviour is lacking. Here we characterize a neuronal circuit in the Drosophila central complex that compares internally generated estimates of the heading and goal angles of the fly-both of which are encoded in world-centred (allocentric) coordinates-to generate a body-centred (egocentric) steering signal. Past work has suggested that the activity of EPG neurons represents the fly's moment-to-moment angular orientation, or heading angle, during navigation2,11. An animal's moment-to-moment heading angle, however, is not always aligned with its goal angle-that is, the allocentric direction in which it wishes to progress forward. We describe FC2 cells12, a second set of neurons in the Drosophila brain with activity that correlates with the fly's goal angle. Focal optogenetic activation of FC2 neurons induces flies to orient along experimenter-defined directions as they walk forward. EPG and FC2 neurons connect monosynaptically to a third neuronal class, PFL3 cells12,13. We found that individual PFL3 cells show conjunctive, spike-rate tuning to both the heading angle and the goal angle during goal-directed navigation. Informed by the anatomy and physiology of these three cell classes, we develop a model that explains how this circuit compares allocentric heading and goal angles to build an egocentric steering signal in the PFL3 output terminals. Quantitative analyses and optogenetic manipulations of PFL3 activity support the model. Finally, using a new navigational memory task, we show that flies expressing disruptors of synaptic transmission in subsets of PFL3 cells have a reduced ability to orient along arbitrary goal directions, with an effect size in quantitative accordance with the prediction of our model. The biological circuit described here reveals how two population-level allocentric signals are compared in the brain to produce an egocentric output signal that is appropriate for motor control.

Kinetic features dictate sensorimotor alignment in the superior colliculus.

The execution of goal-oriented behaviours requires a spatially coherent alignment between sensory and motor maps. The current model for sensorimotor transformation in the superior colliculus relies on the topographic mapping of static spatial receptive fields onto movement endpoints1-6. Here, to experimentally assess the validity of this canonical static model of alignment, we dissected the visuo-motor network in the superior colliculus and performed in vivo intracellular and extracellular recordings across layers, in restrained and unrestrained conditions, to assess both the motor and the visual tuning of individual motor and premotor neurons. We found that collicular motor units have poorly defined visual static spatial receptive fields and respond instead to kinetic visual features, revealing the existence of a direct alignment in vectorial space between sensory and movement vectors, rather than between spatial receptive fields and movement endpoints as canonically hypothesized. We show that a neural network built according to these kinetic alignment principles is ideally placed to sustain ethological behaviours such as the rapid interception of moving and static targets. These findings reveal a novel dimension of the sensorimotor alignment process. By extending the alignment from the static to the kinetic domain this work provides a novel conceptual framework for understanding the nature of sensorimotor convergence and its relevance in guiding goal-directed behaviours.

Transforming a head direction signal into a goal-oriented steering command.

To navigate, we must continuously estimate the direction we are headed in, and we must correct deviations from our goal1. Direction estimation is accomplished by ring attractor networks in the head direction system2,3. However, we do not fully understand how the sense of direction is used to guide action. Drosophila connectome analyses4,5 reveal three cell populations (PFL3R, PFL3L and PFL2) that connect the head direction system to the locomotor system. Here we use imaging, electrophysiology and chemogenetic stimulation during navigation to show how these populations function. Each population receives a shifted copy of the head direction vector, such that their three reference frames are shifted approximately 120° relative to each other. Each cell type then compares its own head direction vector with a common goal vector; specifically, it evaluates the congruence of these vectors via a nonlinear transformation. The output of all three cell populations is then combined to generate locomotor commands. PFL3R cells are recruited when the fly is oriented to the left of its goal, and their activity drives rightward turning; the reverse is true for PFL3L. Meanwhile, PFL2 cells increase steering speed, and are recruited when the fly is oriented far from its goal. PFL2 cells adaptively increase the strength of steering as directional error increases, effectively managing the tradeoff between speed and accuracy. Together, our results show how a map of space in the brain can be combined with an internal goal to generate action commands, via a transformation from world-centric coordinates to body-centric coordinates.

Designing a circular carbon and plastics economy for a sustainable future.

The linear production and consumption of plastics today is unsustainable. It creates large amounts of unnecessary and mismanaged waste, pollution and carbon dioxide emissions, undermining global climate targets and the Sustainable Development Goals. This Perspective provides an integrated technological, economic and legal view on how to deliver a circular carbon and plastics economy that minimizes carbon dioxide emissions. Different pathways that maximize recirculation of carbon (dioxide) between plastics waste and feedstocks are outlined, including mechanical, chemical and biological recycling, and those involving the use of biomass and carbon dioxide. Four future scenarios are described, only one of which achieves sufficient greenhouse gas savings in line with global climate targets. Such a bold system change requires 50% reduction in future plastic demand, complete phase-out of fossil-derived plastics, 95% recycling rates of retrievable plastics and use of renewable energy. It is hard to overstate the challenge of achieving this goal. We therefore present a roadmap outlining the scale and timing of the economic and legal interventions that could possibly support this. Assessing the service lifespan and recoverability of plastic products, along with considerations of sufficiency and smart design, can moreover provide design principles to guide future manufacturing, use and disposal of plastics.

Goal-directed learning in adolescence: neurocognitive development and contextual influences.

Adolescence is a time during which we transition to independence, explore new activities and begin pursuit of major life goals. Goal-directed learning, in which we learn to perform actions that enable us to obtain desired outcomes, is central to many of these processes. Currently, our understanding of goal-directed learning in adolescence is itself in a state of transition, with the scientific community grappling with inconsistent results. When we examine metrics of goal-directed learning through the second decade of life, we find that many studies agree there are steady gains in performance in the teenage years, but others report that adolescent goal-directed learning is already adult-like, and some find adolescents can outperform adults. To explain the current variability in results, sophisticated experimental designs are being applied to test learning in different contexts. There is also increasing recognition that individuals of different ages and in different states will draw on different neurocognitive systems to support goal-directed learning. Through adoption of more nuanced approaches, we can be better prepared to recognize and harness adolescent strengths and to decipher the purpose (or goals) of adolescence itself.

Diverse values of nature for sustainability.

Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.

Neural landscape diffusion resolves conflicts between needs across time.

Animals perform flexible goal-directed behaviours to satisfy their basic physiological needs1-12. However, little is known about how unitary behaviours are chosen under conflicting needs. Here we reveal principles by which the brain resolves such conflicts between needs across time. We developed an experimental paradigm in which a hungry and thirsty mouse is given free choices between equidistant food and water. We found that mice collect need-appropriate rewards by structuring their choices into persistent bouts with stochastic transitions. High-density electrophysiological recordings during this behaviour revealed distributed single neuron and neuronal population correlates of a persistent internal goal state guiding future choices of the mouse. We captured these phenomena with a mathematical model describing a global need state that noisily diffuses across a shifting energy landscape. Model simulations successfully predicted behavioural and neural data, including population neural dynamics before choice transitions and in response to optogenetic thirst stimulation. These results provide a general framework for resolving conflicts between needs across time, rooted in the emergent properties of need-dependent state persistence and noise-driven shifts between behavioural goals.

Coral reefs benefit from reduced land-sea impacts under ocean warming.

Coral reef ecosystems are being fundamentally restructured by local human impacts and climate-driven marine heatwaves that trigger mass coral bleaching and mortality1. Reducing local impacts can increase reef resistance to and recovery from bleaching2. However, resource managers lack clear advice on targeted actions that best support coral reefs under climate change3 and sector-based governance means most land- and sea-based management efforts remain siloed4. Here we combine surveys of reef change with a unique 20-year time series of land-sea human impacts that encompassed an unprecedented marine heatwave in Hawai'i. Reefs with increased herbivorous fish populations and reduced land-based impacts, such as wastewater pollution and urban runoff, had positive coral cover trajectories predisturbance. These reefs also experienced a modest reduction in coral mortality following severe heat stress compared to reefs with reduced fish populations and enhanced land-based impacts. Scenario modelling indicated that simultaneously reducing land-sea human impacts results in a three- to sixfold greater probability of a reef having high reef-builder cover four years postdisturbance than if either occurred in isolation. International efforts to protect 30% of Earth's land and ocean ecosystems by 2030 are underway5. Our results reveal that integrated land-sea management could help achieve coastal ocean conservation goals and provide coral reefs with the best opportunity to persist in our changing climate.

A cell-type-specific error-correction signal in the posterior parietal cortex.

Neurons in the posterior parietal cortex contribute to the execution of goal-directed navigation1 and other decision-making tasks2-4. Although molecular studies have catalogued more than 50 cortical cell types5, it remains unclear what distinct functions they have in this area. Here we identified a molecularly defined subset of somatostatin (Sst) inhibitory neurons that, in the mouse posterior parietal cortex, carry a cell-type-specific error-correction signal for navigation. We obtained repeatable experimental access to these cells using an adeno-associated virus in which gene expression is driven by an enhancer that functions specifically in a subset of Sst cells6. We found that during goal-directed navigation in a virtual environment, this subset of Sst neurons activates in a synchronous pattern that is distinct from the activity of surrounding neurons, including other Sst neurons. Using in vivo two-photon photostimulation and ex vivo paired patch-clamp recordings, we show that nearby cells of this Sst subtype excite each other through gap junctions, revealing a self-excitation circuit motif that contributes to the synchronous activity of this cell type. These cells selectively activate as mice execute course corrections for deviations in their virtual heading during navigation towards a reward location, for both self-induced and experimentally induced deviations. We propose that this subtype of Sst neurons provides a self-reinforcing and cell-type-specific error-correction signal in the posterior parietal cortex that may help with the execution and learning of accurate goal-directed navigation trajectories.

Landscape-scale benefits of protected areas for tropical biodiversity.

The United Nations recently agreed to major expansions of global protected areas (PAs) to slow biodiversity declines1. However, although reserves often reduce habitat loss, their efficacy at preserving animal diversity and their influence on biodiversity in surrounding unprotected areas remain unclear2-5. Unregulated hunting can empty PAs of large animals6, illegal tree felling can degrade habitat quality7, and parks can simply displace disturbances such as logging and hunting to unprotected areas of the landscape8 (a phenomenon called leakage). Alternatively, well-functioning PAs could enhance animal diversity within reserves as well as in nearby unprotected sites9 (an effect called spillover). Here we test whether PAs across mega-diverse Southeast Asia contribute to vertebrate conservation inside and outside their boundaries. Reserves increased all facets of bird diversity. Large reserves were also associated with substantially enhanced mammal diversity in the adjacent unprotected landscape. Rather than PAs generating leakage that deteriorated ecological conditions elsewhere, our results are consistent with PAs inducing spillover that benefits biodiversity in surrounding areas. These findings support the United Nations goal of achieving 30% PA coverage by 2030 by demonstrating that PAs are associated with higher vertebrate diversity both inside their boundaries and in the broader landscape.

A cortico-collicular circuit for orienting to shelter during escape.

When faced with predatory threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. Animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions1,2. Although previous work has identified neural mechanisms of escape initiation3,4, it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that the mouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes the shelter-direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP-SC pathway disrupts the orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network because of higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter-direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically constrained spiking network model in which RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP-SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible.

Aligning climate scenarios to emissions inventories shifts global benchmarks.

Taking stock of global progress towards achieving the Paris Agreement requires consistently measuring aggregate national actions and pledges against modelled mitigation pathways1. However, national greenhouse gas inventories (NGHGIs) and scientific assessments of anthropogenic emissions follow different accounting conventions for land-based carbon fluxes resulting in a large difference in the present emission estimates2,3, a gap that will evolve over time. Using state-of-the-art methodologies4 and a land carbon-cycle emulator5, we align the Intergovernmental Panel on Climate Change (IPCC)-assessed mitigation pathways with the NGHGIs to make a comparison. We find that the key global mitigation benchmarks become harder to achieve when calculated using the NGHGI conventions, requiring both earlier net-zero CO2 timing and lower cumulative emissions. Furthermore, weakening natural carbon removal processes such as carbon fertilization can mask anthropogenic land-based removal efforts, with the result that land-based carbon fluxes in NGHGIs may ultimately become sources of emissions by 2100. Our results are important for the Global Stocktake6, suggesting that nations will need to increase the collective ambition of their climate targets to remain consistent with the global temperature goals.

Hippocampal place cells have goal-oriented vector fields during navigation.

The hippocampal cognitive map supports navigation towards, or away from, salient locations in familiar environments1. Although much is known about how the hippocampus encodes location in world-centred coordinates, how it supports flexible navigation is less well understood. We recorded CA1 place cells while rats navigated to a goal on the honeycomb maze2. The maze tests navigation via direct and indirect paths to the goal and allows the directionality of place cells to be assessed at each choice point. Place fields showed strong directional polarization characterized by vector fields that converged to sinks distributed throughout the environment. The distribution of these 'convergence sinks' (ConSinks) was centred near the goal location and the population vector field converged on the goal, providing a strong navigational signal. Changing the goal location led to movement of ConSinks and vector fields towards the new goal. The honeycomb maze allows independent assessment of spatial representation and spatial action in place cell activity and shows how the latter relates to the former. The results suggest that the hippocampus creates a vector-based model to support flexible navigation, allowing animals to select optimal paths to destinations from any location in the environment.

Building an allocentric travelling direction signal via vector computation.

Many behavioural tasks require the manipulation of mathematical vectors, but, outside of computational models1-7, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation7-10, performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks the allocentric travelling angle of a fly, that is, the travelling angle in reference to external cues. Past work has identified neurons in Drosophila8,11-13 and mammals14 that track the heading angle of an animal referenced to external cues (for example, head direction cells), but this new signal illuminates how the sense of space is properly updated when travelling and heading angles differ (for example, when walking sideways). We then characterize a neuronal circuit that performs an egocentric-to-allocentric (that is, body-centred to world-centred) coordinate transformation and vector addition to compute the allocentric travelling direction. This circuit operates by mapping two-dimensional vectors onto sinusoidal patterns of activity across distinct neuronal populations, with the amplitude of the sinusoid representing the length of the vector and its phase representing the angle of the vector. The principles of this circuit may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required.