Danko, A. | bioRxiv Science

bioRxiv2026

CGRP receptor-expressing neurons in the central amygdala contributes to injury-induced pain hypersensitivity

The central nucleus of amygdala (CeA) comprises diverse populations of neurons, forming a complex network responsible for regulating various behavioral responses. Among these, neurons expressing calcitonin gene-related peptide receptors (CGRPR) have emerged as key players in CGRP neuropeptide-mediated pain modulation. While previous studies emphasize CGRPs key role in synaptic plasticity and its connection with pain behavior in the CeA, the precise functional attributes and contributions of CeA-CGRPR-expressing neurons in pain processing remain elusive. This study reveals the co-localization of CGRPR-expressing neurons in the CeA with phosphorylated extracellular signal-regulated kinase (pERK), a marker indicating pain plasticity, in a neuropathic pain model. Electrophysiological assessments of these neurons in slice preparations unveiled heightened intrinsic excitability after sciatic nerve cuff implantation, contingent upon their rostro-caudal positioning within the CeA. Furthermore, our behavioral experiments using chemogenetic inhibition of CeA-CGRPR neurons demonstrated the ability to reverse nerve injury-induced hypersensitivity. Conversely, activating these neurons induced pain-related hypersensitivity even in the absence of injury. Our findings also highlight a sex-specific role of CeA-CGRPR neurons in formalin-induced spontaneous pain response. Collectively, these data reinforce the involvement of CeA-CGRPR neurons in pain processing, contributing to a better understanding of how neural circuits are affected in persistent pain conditions. Significance StatementOur study shows the role of CGRPR-expressing neurons within the CeA during pain processing. Using a cuff-implanted neuropathic mouse model, we discovered that CGRPR-expressing neurons co-localize with phosphorylated extracellular signal-regulated kinase (pERK), a hallmark of pain plasticity, in both male and female mice. Furthermore, our electrophysiological investigations reveal that posterior CeA-CGRPR neurons exhibit increased excitability following sciatic nerve cuff implantation. Importantly, we demonstrate that CeA-CGRPR neurons exert bidirectional effects on pain behavior in mice, irrespective of sex differences in nerve injury-induced pain responses while showing sex-specific spontaneous pain responses in the formalin-induced model. These findings show the role of CeA-CGRPR neurons in pain modulation, underscoring their potential significance in understanding and addressing persistent pain conditions.

neuroscience↗

bioRxiv2022

What causes bird-building collision risk? Seasonal dynamics and weather drivers

Bird-building collisions are a major source of wild bird mortality, with hundreds of millions of fatalities each year in the United States and Canada alone. Here, we use two decades of daily citizen-science monitoring to characterize day-to-day variation in building collisions and determine the factors that predict the highest risk times in two North American cities. We use these analyses to evaluate three potential causes of increased collision risk: heightened migration traffic during benign weather, increased navigational and flight errors during inclement weather, and increased errors in response to highly directional sunlight that enhances reflected images. The seasonal phenology of collisions was consistent across sites and years, with daily collision rates approximately two-fold higher in autumn as compared to spring. During both migration seasons, collision risk was best predicted by the weather conditions at dawn. In spring, peak collision risk occurs on days with warm temperatures, south winds, and a lack of precipitation at dawn. In autumn, peak collision occurs on days with cool temperatures, north winds, high atmospheric pressure, a lack of precipitation, and clear conditions with high visibility. Based on these results, we hypothesize that collisions are influenced by two main weather-driven mechanisms. First, benign weather at dawn with winds that are favorable for migration flight causes an increase in migration traffic in both spring and autumn, creating greater opportunity for collisions to occur. Second, for autumnal migrants, cold clear conditions may cause an additional increase in collision risk. We propose that these conditions may be particularly hazardous in autumn because of the high abundance of naive and diurnal migrants at that time of year. Our analysis also establishes that a relatively small proportion of days (15%) are responsible for 50% of the total collision mortality within a season, highlighting the importance of targeting mitigation strategies to the most hazardous times.

ecology↗