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The origins and consequences of heterogeneous neurons in a molecular oscillator model of the mammalian circadian clock
Author(s) -
Webb Alexis Brooke,
Taylor Stephanie,
Petzold Linda,
Doyle Frank,
Herzog Erik
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.942.1
Subject(s) - oscillation (cell signaling) , neuroscience , circadian clock , synchronization (alternating current) , phenotype , biology , network topology , circadian rhythm , suprachiasmatic nucleus , coupling (piping) , biological system , physics , topology (electrical circuits) , computer science , mathematics , gene , genetics , materials science , combinatorics , metallurgy , operating system
The mammalian suprachiasmatic nuclei (SCN) contain 20,000 neurons capable of generating near 24‐h rhythms. Recent data from functionally isolated SCN neurons show that single cells can exhibit a range of oscillatory phenotypes when removed from their network. The implications of variability in the quality of oscillations between circadian cells remain unknown. We exploited known bifurcations in a set of parameters from an existing deterministic model to reveal their contributions to different behaviors in SCN neurons. By simulating single cells with a range of parameter values, the authors (1) produced a range of oscillatory phenotypes similar to biological cells, (2) found that phenotype was more sensitive to changes in rates of transcription and degradation of Period than to changes in rates of translation and phosphorylation, and (3) determined phenotype‐dependent properties using velocity response curves. The authors next looked for potential biological consequences of building networks from these heterogeneous oscillators and (4) observed that the rate of resynchronization in the network depends on the number and location of damped cells, such that when coupling is reinstated, network topologies in which damped oscillators are highly connected restore rhythmicity and synchrony faster. These results indicate that heterogeneity in oscillatory ability amongst neurons is beneficial and their position within the network can influence the behavior of the system overall. Thus, a range of oscillation types is crucial for a resynchronizing network and damped cells in particular aid the speed of synchronization.