{"doi":"10.1016/j.neuron.2024.08.006","title":"Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons","abstract":"Homeostatic regulation of neuronal activity is essential for robust computation; set-points, such as firing rate, are actively stabilized to compensate for perturbations. The disruption of brain function central to neurodegenerative disease likely arises from impairments of computationally essential set-points. Here, we systematically investigated the effects of tau-mediated neurodegeneration on all known set-points in neuronal activity. We continuously tracked hippocampal neuronal activity across the lifetime of a mouse model of tauopathy. We were unable to detect effects of disease in measures of single-neuron firing activity. By contrast, as tauopathy progressed, there was disruption of network-level neuronal activity, quantified by measuring neuronal pairwise interactions and criticality, a homeostatically controlled, ideal computational regime. Deviations in criticality correlated with symptoms, predicted underlying anatomical pathology, occurred in a sleep-wake-dependent manner, and could be used to reliably classify an animal's genotype. This work illustrates how neurodegeneration may disrupt the computational capacity of neurobiological systems.","journal":"Neuron","year":2024,"id":425682,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":994610,"name":"Clayton A. Farris","orcid":null,"position":1,"is_corresponding":false},{"id":1057704,"name":"Sahara Ensley","orcid":null,"position":2,"is_corresponding":false},{"id":1057082,"name":"Aidan Schneider","orcid":"0000-0002-7928-8654","position":3,"is_corresponding":false},{"id":1223864,"name":"Leandro J. Fosque","orcid":"0000-0003-0638-5514","position":4,"is_corresponding":false},{"id":1169855,"name":"Chao Wang","orcid":"0000-0003-0914-2665","position":5,"is_corresponding":false},{"id":1223865,"name":"Elizabeth I. Tilden","orcid":"0000-0001-6560-3863","position":6,"is_corresponding":false},{"id":1169856,"name":"Yuqi Liu","orcid":"0000-0002-6699-5982","position":7,"is_corresponding":false},{"id":1170367,"name":"Jianhong Tu","orcid":null,"position":8,"is_corresponding":false},{"id":994611,"name":"Halla Elmore","orcid":null,"position":9,"is_corresponding":false},{"id":1170368,"name":"Keenan D. Ronayne","orcid":null,"position":10,"is_corresponding":false},{"id":517192,"name":"Ralf Weßel","orcid":null,"position":11,"is_corresponding":false},{"id":415673,"name":"Eva L. Dyer","orcid":"0000-0002-6962-524X","position":12,"is_corresponding":false},{"id":994609,"name":"Kiran Bhaskaran‐Nair","orcid":null,"position":13,"is_corresponding":false},{"id":27592,"name":"David M. Holtzman","orcid":"0000-0002-3400-0856","position":14,"is_corresponding":false},{"id":264527,"name":"Keith B. Hengen","orcid":"0000-0001-5017-4090","position":15,"is_corresponding":false},{"id":211638,"name":"James N. McGregor","orcid":"0000-0002-5187-0984","position":0,"is_corresponding":true}],"reference_count":129,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"39241778","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}