Neurobiology of Aging, Год журнала: 2023, Номер 125, С. 98 - 108
Опубликована: Фев. 1, 2023
Язык: Английский
Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(18)
Опубликована: Апрель 29, 2022
Significance Brainstem locus coeruleus (LC) noradrenergic neurons produce an arousal-related state characterized by a broadband increase in high-frequency oscillations. This perspective was built upon electrical or optogenetic stimulation that artificially activates LC synchronously. has led to the conceptual model activation is associated with single cortical state. Here, we show natural, spontaneously occurring single-unit activity consists of ensembles largely nonoverlapping dynamics. Spontaneous activations different are states. Our results suggest role controlling type arousal oversimplification. Instead, may control diverse multitude
Язык: Английский
Процитировано
51
Acta Neuropathologica, Год журнала: 2022, Номер 144(4), С. 651 - 676
Опубликована: Авг. 30, 2022
Abstract Tau pathology of the noradrenergic locus coeruleus (LC) is a hallmark several age-related neurodegenerative disorders, including Alzheimer’s disease. However, comprehensive neuropathological examination LC difficult due to its small size and rod-like shape. To investigate cytoarchitecture tau cytoskeletal in relation possible propagation patterns disease-associated an unprecedented large-scale three-dimensional view, we utilized volume immunostaining optical clearing technology combined with light sheet fluorescence microscopy. We examined AT8 + pathological LC/pericoerulear region 20 brains from Braak neurofibrillary tangle (NFT) stage 0–6. demonstrate intriguing morphological complexity heterogeneity cellular structures LC, representing various intracellular stages NFT maturation their diverse transition forms. describe novel morphologies neuronal such as cells fine filamentous somatic protrusions or disintegrating soma. show that gradual dendritic atrophy first sign degeneration tangle-bearing neurons, even preceding axonal lesions. Interestingly, irrespective stage, more advanced dorsal preferentially projects vulnerable forebrain regions disease, like hippocampus neocortical areas, compared ventral projecting cerebellum medulla. Moreover, already precortical 0 3D analysis reveals clustering tendency dendro-dendritic close appositions long axons NFT-bearing join ascending bundle after leaving well processes neurons target 4th ventricle wall. Our study suggests unique cytoarchitecture, comprised densely packed dendritically extensively interconnected network projections, makes human be ideal anatomical template for early accumulation trans-neuronal spreading hyperphosphorylated tau.
Язык: Английский
Процитировано
39
Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 149, С. 105167 - 105167
Опубликована: Апрель 11, 2023
Noradrenergic and cholinergic systems are among the most vulnerable brain in neuropsychiatric diseases of ageing, including Alzheimer's disease, Parkinson's Lewy body dementia, progressive supranuclear palsy. As these fail, they contribute directly to many characteristic cognitive psychiatric symptoms. However, their contribution symptoms is not sufficiently understood, pharmacological interventions targeting noradrenergic have met with mixed success. Part challenge complex neurobiology systems, operating across multiple timescales, non-linear changes adult lifespan disease course. We address challenges a detailed review outlining roles cognition behaviour, how influence disease. By bridging levels analysis, we highlight opportunities for improving drug therapies pursuing personalised medicine strategies.
Язык: Английский
Процитировано
33
Trends in Neurosciences, Год журнала: 2023, Номер 47(2), С. 92 - 105
Опубликована: Дек. 14, 2023
Predictive processing models posit that brains constantly attempt to predict their sensory inputs. Prediction errors signal when these predictions are incorrect and thought be instructive signals drive corrective plasticity. Recent findings support the idea locus coeruleus (LC) - a brain-wide neuromodulatory system several types of prediction error. I discuss how proposing LC global model failures: instances where about world strongly violated. Focusing on cortex, explore utility this in learning rate control, circuit may compute signal, view aid our understanding neurodivergence.
Язык: Английский
Процитировано
29
Neurobiology of Aging, Год журнала: 2023, Номер 125, С. 98 - 108
Опубликована: Фев. 1, 2023
Язык: Английский
Процитировано
27