Ideguchi, Y. | Search bioRxiv

bioRxiv2022

Vascular tortuosity quantification as an outcome metric of the oxygen-induced retinopathy model of ischemic retinopathy

The murine oxygen-induced retinopathy (OIR) model is one of the most widely used animal models of ischemic retinopathy, mimicking hallmark pathophysiology of initial vaso-obliteration (VO) resulting in ischemia that drives neovascularization (NV). In addition to NV and VO, human ischemic retinopathies including Retinopathy of Prematurity (ROP) are characterized by increased vascular tortuosity. Vascular tortuosity is an indicator of disease severity, need to treat, and treatment response in ROP. Current literature investigating novel therapeutics in the OIR model report their effects on NV and VO, but no standardized quantification of vascular tortuosity exists to date despite this metrics relevance to human disease in clinics. The current proof-of-concept study applied a computer-based image analysis algorithm capable of calculating standardized measurements of vascular tortuosity. Quantification of vascular tortuosity correlated with disease activity in OIR analogously to that observed in infants with ROP. Treatment of OIR mice with anti-Vascular Endothelial Growth Factor (aflibercept) rescued vascular tortuosity in the model. Altogether, these data demonstrated that vascular tortuosity is a quantifiable feature of the OIR model and may be used as an outcome measurement in future studies investigating new treatment modalities for retinal ischemia.

neuroscience↗

bioRxiv2022

Novel cerebello-amygdala connections provide missing link between cerebellum and limbic system

The cerebellum is emerging as a powerful regulator of cognitive and affective processing and memory in both humans and animals and has been implicated in affective disorders. How the cerebellum supports affective function remains poorly understood. The short-latency (just a few ms) functional connections that were identified between the cerebellum and amygdala -a structure crucial for the processing of emotion and valence-more than 4 decades ago raise the exciting, yet untested, possibility that a cerebellum-amygdala pathway communicates information important for emotion. The major hurdle in rigorously testing this possibility is the lack of knowledge about the anatomy and functional connectivity of this pathway. Our initial anatomical tracing studies in mice excluded the existence of a direct monosynaptic pathway between cerebellum and amygdala. Using transneuronal tracing techniques, we have identified a novel disynaptic pathway that connects the cerebellar output nuclei to the basolateral amygdala. This pathway recruits the understudied intralaminar thalamus as a node. Using ex vivo optophysiology and super-resolution microscopy, we provide the first evidence for the functionality of the pathway, thus offering a missing mechanistic link between the cerebellum and amygdala. This discovery provides a connectivity blueprint between the cerebellum and a key structure of the limbic system. As such, it is the requisite first step toward obtaining new knowledge about cerebellar function in emotion, thus fundamentally advancing understanding of the neurobiology of emotion, which is perturbed in mental and autism spectrum disorders.

neuroscience↗