New insights from small rhythmic circuits

Marder, Eve; Kedia, Sonal; Morozova, Ekaterina

doi:10.1016/j.conb.2022.102610

Cited by 27 publications

(13 citation statements)

References 105 publications

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“…An open question is what are the sources of variation within the nervous system that give rise to different individuality types? Underlying differences among individuals may include diversity in gene-expression patterns (Casanueva et al, 2012), nervous system structure (Witvliet et al, 2021; Brittin et al, 2021; Linneweber et al, 2020; Churgin et al, 2021), and underlying persistent differences in neruomodulatory parameters that have phenotypic effects under extreme conditions (Marder et al, 2022). It is plausible that some of this variation, which is partially stochastic by nature, may generate different behavioral biases of individuals within isogenic populations.…”

Section: Discussionmentioning

confidence: 99%

Early-life experience reorganizes neuromodulatory regulation of stage-specific behavioral responses and individuality types during development

Nasser

Harel

Stern

2022

Preprint

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Early-life experiences may promote stereotyped behavioral alterations that are dynamic across development time, but also behavioral responses that are variable among individuals, even when initially exposed to the same stimulus. Here, by utilizing longitudinal monitoring of C. elegans individuals throughout development we show that behavioral effects of early-life starvation are exposed during early and late developmental stages and buffered during intermediate stages of development. We further found that both dopamine and serotonin shape the discontinuous behavioral responses by opposite and temporally segregated functions across development time. While dopamine buffers behavioral responses during intermediate developmental stages, serotonin promotes behavioral sensitivity to stress during early and late stages. Interestingly, unsupervised analysis of individual biases across development uncovered multiple individuality types that coexist within stressed and unstressed populations and further identified experience-dependent effects on their composition. These results provide insight into the complex temporal regulation of behavioral plasticity across developmental timescales, structuring shared and unique individual responses to early-life experiences.

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Section: Discussionmentioning

confidence: 99%

Early-life experience reorganizes neuromodulatory regulation of stage-specific behavioral responses and individuality types during development

Nasser

Harel

Stern

2022

Preprint

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“…Therefore, no two brains are identical in their organization, bestowing individuality. This is demonstrated by the important differences across individuals in the parameters defining even the simplest neural function (Edelman & Gally, 2001;Prinz et al, 2004;Gunaratne et al, 2017;Zhang et al, 2020;Marder et al, 2022). This view has highly relevant implications for the neuroscientific field.…”

Section: Emergence Of Individualitymentioning

confidence: 99%

Uncovering the determinants of brain functioning, behavior and their interplay in the light of context

Branchi¹

2023

Preprint

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Notwithstanding the huge progress in molecular and cellular neuroscience, our ability to understand the brain and develop effective treatments promoting mental health is still limited. This can be partially ascribed to the reductionist, deterministic and mechanistic approaches in neuroscience that struggle with the complexity of the central nervous system. Here, I propose the Context theory of constrained systems that reconsiders the relative role of contextual factors and of the genetic, molecular and neural substrates in determining brain functioning and behavior. This framework entails that, first, context is the main driver of behavior and mental states. Second, substrates, from genes to brain areas, have no direct causal link to complex behavioral responses as they can be combined in multiple ways to produce the same response and different responses can impinge on the same substrates. Third, context and biological substrates play distinct roles in determining behavior: context drives behavior, substrates constrain the behavioral repertoire that can be implemented. Fourth, since behavior is the interface between the central nervous system and the environment, it is a privileged level of control and orchestration of brain functioning. These concepts are here illustrated through the Kitchen metaphor of the brain. This theoretical framework calls for the revision of key concepts in neuroscience and biological psychiatry, including causality, specificity and individuality. Moreover, at the clinical level, it proposes treatments inducing behavioral changes through contextual interventions as having the highest impact to reorganize the complexity of the human mind and to achieve a long-lasting improvement in mental health.

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“…Although CPGs can produce rhythmic output without rhythmic input, modulatory input is often required to configure CPGs into an active state. Additionally, beyond simply turning on or off, CPGs are often "multifunctional, " in that they produce different outputs to adapt to changes in the internal and external environments (Briggman and Kristan, 2008;Benjamin, 2012;Daur et al, 2016;Marder et al, 2022). In some cases, the source of modulation is intrinsic to the CPG and a necessary component of motor output (Katz, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Small circuits, particularly those underlying rhythmic behaviors, with their identified neurons, have enabled many important insights into circuit function and plasticity (Calabrese et al, 2016;Cropper et al, 2018;Katz and Quinlan, 2019;Marder et al, 2022). Similar to the accessibility of identified circuit neurons, several invertebrate preparations also have relatively small populations of modulatory PNs which are accessible to electrophysiological approaches (Rosen et al, 1991;Heinrich, 2002;Mesce et al, 2008;Nusbaum, 2008).…”

Section: Introductionmentioning

confidence: 99%

Neural circuit regulation by identified modulatory projection neurons

Blitz

2023

Front. Neurosci.

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Rhythmic behaviors (e.g., walking, breathing, and chewing) are produced by central pattern generator (CPG) circuits. These circuits are highly dynamic due to a multitude of input they receive from hormones, sensory neurons, and modulatory projection neurons. Such inputs not only turn CPG circuits on and off, but they adjust their synaptic and cellular properties to select behaviorally relevant outputs that last from seconds to hours. Similar to the contributions of fully identified connectomes to establishing general principles of circuit function and flexibility, identified modulatory neurons have enabled key insights into neural circuit modulation. For instance, while bath-applying neuromodulators continues to be an important approach to studying neural circuit modulation, this approach does not always mimic the neural circuit response to neuronal release of the same modulator. There is additional complexity in the actions of neuronally-released modulators due to: (1) the prevalence of co-transmitters, (2) local- and long-distance feedback regulating the timing of (co-)release, and (3) differential regulation of co-transmitter release. Identifying the physiological stimuli (e.g., identified sensory neurons) that activate modulatory projection neurons has demonstrated multiple “modulatory codes” for selecting particular circuit outputs. In some cases, population coding occurs, and in others circuit output is determined by the firing pattern and rate of the modulatory projection neurons. The ability to perform electrophysiological recordings and manipulations of small populations of identified neurons at multiple levels of rhythmic motor systems remains an important approach for determining the cellular and synaptic mechanisms underlying the rapid adaptability of rhythmic neural circuits.

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New insights from small rhythmic circuits

Cited by 27 publications

References 105 publications

Early-life experience reorganizes neuromodulatory regulation of stage-specific behavioral responses and individuality types during development

Early-life experience reorganizes neuromodulatory regulation of stage-specific behavioral responses and individuality types during development

Uncovering the determinants of brain functioning, behavior and their interplay in the light of context

Neural circuit regulation by identified modulatory projection neurons

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