Multiple bursting patterns in Lateral Habenula neurons: experiments and computational model

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Lateral habenula neurons exhibit diverse square-wave, triangular, and parabolic bursting patterns, which a computational model reproduces by identifying a saddle-node homoclinic bifurcation that organizes these distinct dynamic states.

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The study examines bursting activity in lateral habenula (LHb) neurons, using ex vivo recordings analyzed through a dynamical-systems framework to characterize how bursting patterns relate to aversive signaling. The authors report that LHb neurons exhibit multiple bursting types, including square-wave, parabolic, and transitional triangular bursting, and that different patterns can occur within the same neuron, implying distinct dynamic states; a key caveat is that the work is based on idealized modeling and ex vivo observations rather than direct in vivo validation. They propose a multiple-timescale dynamical model that reproduces the three observed bursting patterns and identifies a saddle-node homoclinic bifurcation as an organizing point separating two primary bursting regimes and enabling emergence of the third pattern. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

The Lateral Habenula (LHb) is a small brain structure specialized in encoding aversive signals. Bursting activity in the LHb has been consistently linked to mood regulation, with increased bursting activity proposed to promote depressive behaviors. Bursting is a complex dynamic process that has been extensively studied and modeled in other neuronal contexts. However, at the LHb this type of activity has typically been described only as transient periods of high frequency firing. Here, to provide a deeper understanding of LHb bursting, we analyzed this activity from the perspective of dynamical systems. Ex vivo, LHb neurons display a variety of bursting patterns, characterized at one extreme by a dominating square-wave type and in other by parabolic type, plus transitional forms referred to as triangular bursting. Notably, these bursting patterns, which reflect different LHb output modes, can occur within the same neuron, suggesting that they may correspond to distinct dynamic states of the same LHb neuron. To capture these complex behaviors, we propose an idealized multiple-timescale dynamical model. This model successfully reproduces the three main bursting patterns observed in experimental data. Furthermore, we identify a special point in the parameter space, termed the saddle-node homoclinic bifurcation, which acts as an organizing center demarcating the boundary between the two primary bursting patterns and around which the third pattern appear. Our model suggests that LHb bursting activity is structured around distinct dynamic states with potentially diverse and unexplored impacts on mood regulation. By providing new insights into the dynamic principles underlying LHb bursting, this framework may advance our understanding of its biological significance.
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Abstract The Lateral Habenula (LHb) is a small brain structure specialized in encoding aversive signals. Bursting activity in the LHb has been consistently linked to mood regulation, with increased bursting activity proposed to promote depressive behaviors. Bursting is a complex dynamic process that has been extensively studied and modeled in other neuronal contexts. However, at the LHb this type of activity has typically been described only as transient periods of high frequency firing. Here, to provide a deeper understanding of LHb bursting, we analyzed this activity from the perspective of dynamical systems. Ex vivo, LHb neurons display a variety of bursting patterns, characterized at one extreme by a dominating square-wave type and in other by parabolic type, plus transitional forms referred to as triangular bursting. Notably, these bursting patterns, which reflect different LHb output modes, can occur within the same neuron, suggesting that they may correspond to distinct dynamic states of the same LHb neuron. To capture these complex behaviors, we propose an idealized multiple-timescale dynamical model. This model successfully reproduces the three main bursting patterns observed in experimental data. Furthermore, we identify a special point in the parameter space, termed the saddle-node homoclinic bifurcation, which acts as an organizing center demarcating the boundary between the two primary bursting patterns and around which the third pattern appear. Our model suggests that LHb bursting activity is structured around distinct dynamic states with potentially diverse and unexplored impacts on mood regulation. By providing new insights into the dynamic principles underlying LHb bursting, this framework may advance our understanding of its biological significance. Competing Interest Statement The authors have declared no competing interest. Footnotes There were significant changes to the manuscript, including title, abstract, additional figures, and evolved understanding of the topic - all while maintaining the same research object and experimental data.

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