Biology subjects

Haggerty, K.

Publications and source records attributed to Haggerty, K..

3 recordsLinked to original sources

bioRxiv2026

Atf6-/- mouse photoreceptors exhibit novel ciliary rootlet defect

ATF6 is a regulator of the Unfolded Protein Response that maintains cellular homeostasis during ER stress. In patients, ATF6 mutations cause photoreceptor dystrophy and sensorineural hearing loss. Atf6-/- mice develop progressive hearing loss with stereocilia disorganization and mild retinal dysfunction, suggesting that ATF6 loss may impair the structural integrity of sensory cells. To test this possibility, we analyzed the retinal ultrastructure of Atf6-/- mouse photoreceptors using transmission electron microscopy and identified a novel defect in which the ciliary rootlet is unbundled, disorganized, and possibly detached from the basal body. These findings demonstrate that ATF6 is essential for maintaining the structural organization of the photoreceptor ciliary apparatus, linking ER proteostasis to cytoskeletal integrity and providing a potential mechanistic basis for the progressive degeneration of photoreceptor outer segments and stereocilia observed in ATF6-deficient patients.

cell biology↗

bioRxiv2026

Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability

IntroductionWe present here a methodology for morphometric analysis of the substantia nigra (SN), the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and their respective structural brain circuits. MethodsOur analyses were based on multimodal T1-weighted MRI and diffusion MRI (dMRI) segmentation and tractography in 12 human subjects drawn from the Human Connectome Project (HCP) repository. ResultsWe were able to demonstrate strong connections of the SN, VTA and DRN with several brain regions, in particular the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. More specifically, we created comprehensive visualizations of the SN and VTA dopaminergic as well as the DRN serotonergic structural circuits in the human brain, which, although preliminary, demonstrate the potential of multimodal neuroimaging to investigate these circuits quantitatively in clinical conditions. Finally, we created a pilot dataset for the most frequently observed structural connections, specifically those that were present more than 92% of the time among all subjects. Discussion This pilot morphometric report examines the structural circuits of the SN, VTA and DRN, which are critically involved in several biobehaviors and clinical conditions such as addiction, stress, Parkinsons disease (PD), schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, mood disorders, COVID-19 and long COVID. Importantly, the strong structural connectivity of the DLPFC and cerebellum with the SN, VTA and DRN is expected to be a potential target of noninvasive neuromodulation treatments in neuropsychiatry. Our findings demonstrate the potential of current clinical multimodal neuroimaging to delineate the dopaminergic (DA) and serotonergic (5-HT) circuits in the human brain in clinical conditions.

neuroscience↗

bioRxiv2025

Neuroanatomy of catecholaminergic circuits in the brainstem and hypothalamus using T1-weighted and diffusion magnetic resonance imaging in humans: implications for brain-immune interactions, cardiovascular disease, neuropsychiatric disorders, stress response, and COVID-19

Neuroimaging allows the study of brain structures that previously were undetectable due to their small size and location. Herein we focused on the core catecholaminergic circuitries in the human brain, involving the coerulean noradrenergic (or norepi-nephrine, NE) and dopaminergic (DA) systems. Using T1-weighted MRI morphometry and dMRI tractography, this study was carried out in one post-mortem human ultra-high-resolution dataset of the brainstem and diencephalon and in healthy human datasets from the Human Connectome Project repository. We investigated 26 connections of brainstem origin (13 in the left side and 13 in the right side) associated with the NE and DA circuitries. We delineated the coerulean NE and DA core central catechol-aminergic circuitries of the brainstem and hypothalamus in the post-mortem dataset, including all targeted fiber connections. Importantly, this was also achieved in the HCP datasets. These results emphasize the importance of multispectral neuroimaging in the study of chemical neuroanatomical circuitries and its application in clinical conditions such as cardiovascular disease, major depression, schizophrenia, and other disorders associated with chronic stress and brain-immune interactions such as COVID-19.

neuroscience↗