Neurobiology and Changing Ecosystems: Mechanisms Underlying Responses to Human-Generated Environmental Impacts.

Human generated environmental change profoundly affects organisms that reside across diverse ecosystems. Although nervous systems evolved to flexibly sense, respond, and adapt to environmental change, it is unclear whether the rapid rate of environmental change outpaces the adaptive capacity of complex nervous systems. Here, we explore neural systems mediating responses to, or impacted by, changing environments, such as those induced by global heating, sensory pollution, and changing habitation zones. We focus on rising temperature and accelerated changes in environments that impact sensory experience as examples of perturbations that directly or indirectly impact neural function, respectively. We also explore a mechanism involved in cross-species interactions that arises from changing habitation zones. We demonstrate that anthropogenic influences on neurons, circuits, and behaviors are widespread across taxa and require further scientific investigation to understand principles underlying neural resilience to accelerating environmental change.SIGNIFICANCE STATEMENT Neural systems evolved over hundreds of millions of years to allow organisms to sense and respond to their environments - to be receptive and responsive, yet flexible. Recent rapid, human-generated environmental changes are testing the limits of the adaptive capacity of neural systems. This presents an opportunity and an urgency to understand how neurobiological processes, including molecular, cellular, and circuit-level mechanisms, are vulnerable or resilient to changing environmental conditions. We showcase examples that range from molecular to circuit to behavioral levels of analysis across several model species, framing a broad neuroscientific approach to explore topics of neural adaptation, plasticity, and resilience. We believe this emerging scientific area is of great societal and scientific importance and will provide a unique opportunity to reexamine our understanding of neural adaptation and the mechanisms underlying neural resilience.

Neurobiology and changing ecosystems: Toward understanding the impact of anthropogenic influences on neurons and circuits.

Rapid anthropogenic environmental changes, including those due to habitat contamination, degradation, and climate change, have far-reaching effects on biological systems that may outpace animals' adaptive responses. Neurobiological systems mediate interactions between animals and their environments and evolved over millions of years to detect and respond to change. To gain an understanding of the adaptive capacity of nervous systems given an unprecedented pace of environmental change, mechanisms of physiology and behavior at the cellular and biophysical level must be examined. While behavioral changes resulting from anthropogenic activity are becoming increasingly described, identification and examination of the cellular, molecular, and circuit-level processes underlying those changes are profoundly underexplored. Hence, the field of neuroscience lacks predictive frameworks to describe which neurobiological systems may be resilient or vulnerable to rapidly changing ecosystems, or what modes of adaptation are represented in our natural world. In this review, we highlight examples of animal behavior modification and corresponding nervous system adaptation in response to rapid environmental change. The underlying cellular, molecular, and circuit-level component processes underlying these behaviors are not known and emphasize the unmet need for rigorous scientific enquiry into the neurobiology of changing ecosystems.

Systems Neuroscience of Natural Behaviors in Rodents.

Animals evolved in complex environments, producing a wide range of behaviors, including navigation, foraging, prey capture, and conspecific interactions, which vary over timescales ranging from milliseconds to days. Historically, these behaviors have been the focus of study for ecology and ethology, while systems neuroscience has largely focused on short timescale behaviors that can be repeated thousands of times and occur in highly artificial environments. Thanks to recent advances in machine learning, miniaturization, and computation, it is newly possible to study freely moving animals in more natural conditions while applying systems techniques: performing temporally specific perturbations, modeling behavioral strategies, and recording from large numbers of neurons while animals are freely moving. The authors of this review are a group of scientists with deep appreciation for the common aims of systems neuroscience, ecology, and ethology. We believe it is an extremely exciting time to be a neuroscientist, as we have an opportunity to grow as a field, to embrace interdisciplinary, open, collaborative research to provide new insights and allow researchers to link knowledge across disciplines, species, and scales. Here we discuss the origins of ethology, ecology, and systems neuroscience in the context of our own work and highlight how combining approaches across these fields has provided fresh insights into our research. We hope this review facilitates some of these interactions and alliances and helps us all do even better science, together.

Dynamics of gaze control during prey capture in freely moving mice.

Many studies of visual processing are conducted in constrained conditions such as head- and gaze-fixation, and therefore less is known about how animals actively acquire visual information in natural contexts. To determine how mice target their gaze during natural behavior, we measured head and bilateral eye movements in mice performing prey capture, an ethological behavior that engages vision. We found that the majority of eye movements are compensatory for head movements, thereby serving to stabilize the visual scene. During movement, however, periods of stabilization are interspersed with non-compensatory saccades that abruptly shift gaze position. Notably, these saccades do not preferentially target the prey location. Rather, orienting movements are driven by the head, with the eyes following in coordination to sequentially stabilize and recenter the gaze. These findings relate eye movements in the mouse to other species, and provide a foundation for studying active vision during ethological behaviors in the mouse.

As you read this sentence, your eyes will move automatically from one word to the next, while your head remains still. Moving your eyes enables you to view each word using your central ­ as opposed to peripheral ­ vision. Central vision allows you to see objects in fine detail. It relies on a specialized area of the retina called the fovea. When you move your eyes across a page, you keep the images of the words you are currently reading on the fovea. This provides the detailed vision required for reading. The same process works for tracking moving objects. When watching a bird fly across the sky, you can track its progress by moving your eyes to keep the bird in the center of your visual field, over the fovea. But the majority of mammals do not have a fovea, and yet are still able to track moving targets. Think of a lion hunting a gazelle, for instance, or a cat stalking a mouse. Even mice themselves can track and capture insect prey such as crickets, despite not having a fovea. And yet, exactly how they do this is unknown. This is particularly surprising given that mice have long been used to study the neural basis of vision. By fitting mice with miniature head-mounted cameras, Michaiel et al. now reveal how the rodents track and capture moving crickets. It turns out that unlike animals with a fovea, mice do not use eye movements to track moving objects. Instead, when a mouse wants to look at something new, it moves its head to point at the target. The eyes then follow and 'land' on the target. In essence, head movements lead the way and the eyes catch up afterwards. These findings are consistent with the idea that mammals with large heads evolved eye movements to overcome the energy costs of turning the head whenever they want to look at something new. For small animals, moving the head is less energetically expensive. As a result, being able to move the eyes independent of the head is unnecessary. Future work could use a combination of behavioral experiments and brain recordings to reveal how visual areas of the brain process what an animal is seeing in real time.

A Hallucinogenic Serotonin-2A Receptor Agonist Reduces Visual Response Gain and Alters Temporal Dynamics in Mouse V1.

Sensory perception arises from the integration of externally and internally driven representations of the world. Disrupted balance of these representations can lead to perceptual deficits and hallucinations. The serotonin-2A receptor (5-HT2AR) is associated with such perceptual alterations, both in its role in schizophrenia and in the action of hallucinogenic drugs. Despite this powerful influence on perception, relatively little is known about how serotonergic hallucinogens influence sensory processing in the neocortex. Using widefield and two-photon calcium imaging and single-unit electrophysiology in awake mice, we find that administration of the hallucinogenic selective 5-HT2AR agonist DOI (2,5-dimethoxy-4-iodoamphetamine) leads to a net reduction in visual response amplitude and surround suppression in primary visual cortex, as well as disrupted temporal dynamics. However, basic retinotopic organization, tuning properties, and receptive field structure remain intact. Our results provide support for models of hallucinations in which reduced bottom-up sensory drive is a key factor leading to altered perception.