Heterogeneity of neuronal properties determines the collective behavior of the neurons in the suprachiasmatic nucleus

Gu, C.; Wang, Ping; Weng, Tong Feng; Yang, Hui Jie; Rohling, Jos H. T.

doi:10.3934/mbe.2019092

Cited by 15 publications

(15 citation statements)

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“…This raises an interesting question: why would natural selection favor the evolution of heritable mechanisms to drive period heterogeneity over entirely stochastically driven heterogeneity? We hypothesize that, although period heterogeneity can be functionally beneficial [10][11][12][13][14][15][16][17][18], very large heterogeneity can negatively influence clock functionality as well [12,13,16]. Entirely stochastically driven…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies revealed that such period heterogeneity is not restricted to the SCN but is also observed in mammalian peripheral clock cells [5,6] as well as in Drosophila clock cells [7] and plants [8,9]. The ubiquity of this phenomenon suggests that heterogeneity may be functionally relevant for circadian clocks [10][11][12][13][14][15][16][17][18], thus likely being a substrate for natural selection. Interestingly, the observed period heterogeneity among circadian clock cells within an organism cannot be entirely attributed to functionally different cell types, as cells of the same subtype (clonal cells) also exhibit such variation [5,6].…”

Section: Introductionmentioning

confidence: 99%

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Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

2020

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A ubiquitous feature of the circadian clock across life forms is its organization as a network of cellular oscillators, with individual cellular oscillators within the network often exhibiting considerable heterogeneity in their intrinsic periods. The interaction of coupling and heterogeneity in circadian clock networks is hypothesized to influence clock's entrainability, but our knowledge of mechanisms governing period heterogeneity within circadian clock networks remains largely elusive. In this study, we aimed to explore the principles that underlie intercellular period variation in circadian clock networks (clonal period heterogeneity). To this end, we employed a laboratory selection approach and derived a panel of 25 clonal cell populations exhibiting circadian periods ranging from 22 to 28 h. We report that a single parent clone can produce progeny clones with a wide distribution of circadian periods, and this heterogeneity, in addition to being stochastically driven, has a heritable component. By quantifying the expression of 20 circadian clock and clock-associated genes across our clone panel, we found that inheritance of expression patterns in at least three clock genes might govern clonal period heterogeneity in circadian clock networks. Furthermore, we provide evidence suggesting that heritable epigenetic variation in gene expression regulation might underlie period heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

2020

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“…Heterogeneity in cellular and synaptic properties is of course expected in biological systems, but there is increasing evidence that this is a cultivated property of neuronal networks rather than arising solely from inescapable random variability. Indeed, heterogeneity in cellular and synaptic properties has been credited with improving the sensitivity, efficiency, and information content of neuronal ensembles (Lengler et al, 2013 ; Zohar et al, 2013 ) and regulating the balance between network robustness and flexibility (Gu et al, 2019 ). The advantages of parameter heterogeneity observed in artificial systems models are indicating a broader emerging principle of biomimetic design: considerable computational power and robustness may be achievable by relaxing control over critical variables and subsequently reconstructing the required specificity through effective sampling strategies.…”

Section: Theoretical Capacities Of Olfactory Bulb Circuitsmentioning

confidence: 99%

A Systematic Framework for Olfactory Bulb Signal Transformations

Cleland

Borthakur

2020

Front. Comput. Neurosci.

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We describe an integrated theory of olfactory systems operation that incorporates experimental findings across scales, stages, and methods of analysis into a common framework. In particular, we consider the multiple stages of olfactory signal processing as a collective system, in which each stage samples selectively from its antecedents. We propose that, following the signal conditioning operations of the nasal epithelium and glomerular-layer circuitry, the plastic external plexiform layer of the olfactory bulb effects a process of category learning-the basis for extracting meaningful, quasi-discrete odor representations from the metric space of undifferentiated olfactory quality. Moreover, this early categorization process also resolves the foundational problem of how odors of interest can be recognized in the presence of strong competitive interference from simultaneously encountered background odorants. This problem is fundamentally constraining on early-stage olfactory encoding strategies and must be resolved if these strategies and their underlying mechanisms are to be understood. Multiscale general theories of olfactory systems operation are essential in order to leverage the analytical advantages of engineered approaches together with our expanding capacity to interrogate biological systems.

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“…While this question falls within the realms of 'ultimate' questions (Laland et al, 2011), we present a possible hypothesis. Although period heterogeneity may be beneficial for circadian clock functions (Jagota et al, 2000;Schaap et al, 2003;Gonze et al, 2005;Bernard et al, 2007;Inagaki et al, 2007;VanderLeest et al, 2007;Gu et al, 2016Gu et al, , 2019, very large heterogeneity can also lead to reduction in amplitude, synchronization and entrainability of the clock (Gonze et al, 2005;Bernard et al, 2007;Gu et al, 2016). Stochastic mechanisms may lead to very large variation in inter-cellular/oscillator period which would be detrimental to the network dynamics, whereas heritable mechanisms may impose phenotypic constraints (Wagner,9 2011) within which period-heterogeneity can be maintained thereby being favoured by natural selection.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies revealed that such period-heterogeneity is not restricted to the SCN alone, but is also characteristic of mammalian peripheral clock cells (Nagoshi et al, 2004;Leise et al, 2012) as well as of clock cells in Drosophila (Sabado et al, 2017) and plants (Yakir et al, 2011;Muranaka and Oyama, 2016). The ubiquity of this network feature suggests that heterogeneity may be functionally relevant for circadian clocks (Jagota et al, 2000;Schaap et al, 2003;Gonze et al, 2005;Bernar0d et al, 2007;Inagaki et al, 2007;VanderLeest et al, 2007;Gu et al, 2016Gu et al, , 2019, thus likely being a substrate for natural selection. Interestingly, the observed period-heterogeneity among circadian clock cells within an organism cannot be entirely attributed to functional differentiation of cell subtypes as clonal cells of the same subtype also exhibit such variation (Nagoshi et al, 2004;Leise et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Heritable gene expression variability governs clonal heterogeneity in circadian period

Nikhil

Korge

Kramer

2019

Preprint

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11A ubiquitous feature of circadian clocks across life forms is its organization as a network of 12 coupled cellular oscillators. Individual cellular oscillators of the network often exhibit a 13 considerable degree of heterogeneity in their intrinsic periods. While the interaction of coupling 14 and heterogeneity in circadian clock networks is hypothesized to influence clock's entrainability, 15 our knowledge of mechanisms governing network heterogeneity remains elusive. In this study, 16 we aimed to explore the principles that underlie inter-cellular period variation in circadian clock 17 networks (clonal period-heterogeneity). To this end, we employed a laboratory selection 18 approach and derived a panel of 25 clonal cell populations exhibiting circadian periods ranging 19 from 22 h to 28 h. We report that while a single parent clone can produce progeny clones with a 20 wide distribution of circadian periods, heterogeneity is not entirely stochastically driven but has 21 a strong heritable component. By quantifying the expression of 20 circadian clock and clock-22 associated genes across our panel, we found that inheritance of different expression patterns in 23 at least three clock genes might govern clonal period-heterogeneity in circadian clock networks. 24 Furthermore, we provide preliminary evidence suggesting that epigenetic variation might 25 underlie such gene expression variation. 26 27 Evans et al., 2018). In this study, we aimed to explore the possible mechanisms underlying clonal-55 heterogeneity of circadian period in human circadian oscillator cells. 56 We hypothesised that clonal period-heterogeneity in mammalian cells is due to a) stochastic 57 variation (Geva-Zatorsky et al., 2006; Chang et al., 2008; Brock, Chang and Huang, 2009; Frank 58 and Rosner, 2012) and/or b) heritable variation (Dubnau and Losick, 2006; Gordon et al., 2009, 59 2013). Since the term 'stochastic' is used in the context of both non-heritable (external noise and 60 gene expression noise) as well as heritable gene expression variation (epigenetic stochasticity), 61 for the rest of this manuscript we define 'stochasticity' as any non-heritable variation (both 62 internal and external). To test the two hypothesis outlined above, we employed a laboratory 63 selection approach and derived a panel of 25 clonal cell lines (from a common ancestral/founding 64 culture) exhibiting a range of periods between 22h and 28h. We observed that the period-65 heterogeneity among progeny clones stemming from a single parent cell is not entirely stochastic 66 but has a substantial heritable component. We then measured expression of 20 clock and clock-67 associated genes in our panel and observed that variation in gene expression levels of at least 68 three clock genes (transcription factors) might underlie clonal period-heterogeneity. 69 Furthermore, we provide preliminary evidence that epigenetic variation might govern the 70 observed clonal-variation in gene expression. 71 72 73 74 75 157 period while D...

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Heterogeneity of neuronal properties determines the collective behavior of the neurons in the suprachiasmatic nucleus

Cited by 15 publications

References 66 publications

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

A Systematic Framework for Olfactory Bulb Signal Transformations

Heritable gene expression variability governs clonal heterogeneity in circadian period

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