Multiple bursting patterns in lateral habenula neurons: Experiments and computational model

The lateral habenula (LHb) is a small brain structure specialized in encoding aversive signals. Elevated bursting in the LHb has been linked to depressive-like behaviours in animal models. Bursting is a complex dynamic process that has been extensively studied and modelled in neuronal contexts. However, in the LHb, bursting activity has typically been described only as transient periods of high-frequency firing. Here, to provide a deeper understanding of LHb bursting, we analysed it from the perspective of dynamical systems. Ex vivo, LHb neurons display a variety of bursting patterns, characterized at one extreme by square wave-like bursts and at the other by parabolic bursts, plus transitional forms referred to as triangular bursts. Notably, these bursting patterns, which reflect different LHb output modes, can occur within the same neuron, reflecting distinct dynamic states. In particular, membrane hyperpolarization selectively promotes square-wave-type bursts, rather than triangular or parabolic ones. To capture these complex behaviours, 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 centre demarcating the boundary between the two primary bursting patterns and around which the third pattern appears. 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 principles underlying LHb bursting, this framework may advance our understanding of its biological significance. KEY POINTS: Bursting activity of the brain nucleus of the lateral habenula has been linked to depressive states. Using brain slice experiments, we identified three key burst types: square wave-like, parabolic and intermediate 'triangular' patterns. These patterns likely represent different functional modes of the same neuron rather than different neuron types. A mathematical model was developed that replicates these patterns and reveals a critical transition point that organizes their dynamics. This framework offers new insight into how LHb bursting activity is organized and could potentially guide future treatments for depression.