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Nature Mar 2024The glymphatic movement of fluid through the brain removes metabolic waste. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions...
The glymphatic movement of fluid through the brain removes metabolic waste. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.
Topics: Animals; Mice; Alzheimer Disease; Amyloid; Aquaporin 4; Astrocytes; Brain; Cerebrospinal Fluid; Disease Models, Animal; Extracellular Fluid; Glymphatic System; Interneurons; Vasoactive Intestinal Peptide; Cerebral Cortex; Gamma Rhythm; Electric Stimulation
PubMed: 38418876
DOI: 10.1038/s41586-024-07132-6 -
Nature Jun 2023The anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal...
The anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal dynamics are driven by interactions between discrete, functionally specialized cell populations connected by a complex array of axonal fibres. However, predictions from neural field theory, an established mathematical framework for modelling large-scale brain activity, suggest that the geometry of the brain may represent a more fundamental constraint on dynamics than complex interregional connectivity. Here, we confirm these theoretical predictions by analysing human magnetic resonance imaging data acquired under spontaneous and diverse task-evoked conditions. Specifically, we show that cortical and subcortical activity can be parsimoniously understood as resulting from excitations of fundamental, resonant modes of the brain's geometry (that is, its shape) rather than from modes of complex interregional connectivity, as classically assumed. We then use these geometric modes to show that task-evoked activations across over 10,000 brain maps are not confined to focal areas, as widely believed, but instead excite brain-wide modes with wavelengths spanning over 60 mm. Finally, we confirm predictions that the close link between geometry and function is explained by a dominant role for wave-like activity, showing that wave dynamics can reproduce numerous canonical spatiotemporal properties of spontaneous and evoked recordings. Our findings challenge prevailing views and identify a previously underappreciated role of geometry in shaping function, as predicted by a unifying and physically principled model of brain-wide dynamics.
Topics: Humans; Axons; Brain; Brain Mapping; Magnetic Resonance Imaging; Neurons
PubMed: 37258669
DOI: 10.1038/s41586-023-06098-1 -
Science (New York, N.Y.) Oct 2023Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal...
Episodic memory involves learning and recalling associations between items and their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions to be made. The mechanisms that support these associative and predictive aspects of memory are not yet understood. In this study, we used an optogenetic manipulation to perturb the sequential structure, but not global network dynamics, of place cells as rats traversed specific spatial trajectories. This perturbation abolished replay of those trajectories and the development of predictive representations, leading to impaired learning of new optimal trajectories during memory-guided navigation. However, place cell assembly reactivation and reward-context associative learning were unaffected. Our results show a mechanistic dissociation between two complementary hippocampal codes: an associative code (through coactivity) and a predictive code (through sequences).
Topics: Animals; Rats; Conditioning, Classical; Hippocampus; Memory, Episodic; Mental Recall; Optogenetics; Theta Rhythm; Male; Rats, Long-Evans; Association Learning
PubMed: 37856604
DOI: 10.1126/science.adi8237