| First Author | McGregor JN | Year | 2024 |
| Journal | Neuron | PubMed ID | 39241778 |
| Mgi Jnum | J:354801 | Mgi Id | MGI:7736452 |
| Doi | 10.1016/j.neuron.2024.08.006 | Citation | McGregor JN, et al. (2024) Failure in a population: Tauopathy disrupts homeostatic set-points in emergent dynamics despite stability in the constituent neurons. Neuron |
| abstractText | 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. |
