Brain-Wide Neural Dynamics Underlying Looming-Evoked Escapes and Spontaneous Exploration

Abstract

Behavior is generated via brain-wide coordination of neural circuits. But until recently, it was difficult to analyze neural dynamics at cellular resolution throughout the brain during behavior. With the genetic and optical accessibility of the larval zebrafish, however, we are now beginning to dissect neural circuits on larger scales. Here, I describe the neural origins of two prominent innate behaviors of the larval zebrafish: (1) looming-evoked escape behavior and (2) a self-generated exploratory behavior. In zebrafish, punctuated mechanosensory stimuli, signaling proximal threats, elicit escape behaviors that rely on a compact neural circuit. Visual identification of threats, however, is more complex: instead of detecting an impulse-like stimulus, danger must be recognized by computations on the spatiotemporal properties of visual scenes. Here, I characterize behavioral responses to visual stimuli simulating predator approach using a high-speed, closed-loop system that enables precise control over the visual environment of free-swimming fish. I report that the visual system alone recruits lateralized, rapid escape maneuvers in response to looming but not static stimuli. Brain-wide calcium imaging isolated the optic tectum as an important visual center processing looming stimuli, with ensemble activity encoding escape latency. Finally, ablations of hindbrain circuitry confirmed that visual and mechanosensory modalities share a premotor output network. In the absence of specific stimuli, however, animals continue to exhibit rich self-generated behavior. In featureless environments, fish exhibit stereotypical behavioral sequences, which consist of repeated turns in one direction followed by stochastic switches to repeated turns in the other direction. Using whole-brain imaging in behaving animals, we found antisymmetric activity in distinct hindbrain populations that was ipsilaterally correlated with turning and exhibited slow time courses well-matched to behavioral sequences. These populations correspond to the “hindbrain oscillator” (HBO), and cell ablations demonstrated a causal role for the HBO in determining the statistics of spontaneous swimming. We revealed that the HBO comprises separate glutamatergic and GABAergic clusters interacting across the midline, suggesting a mutual-inhibitory circuit motif shaping HBO dynamics and downstream behavior. These findings establish a circuit underlying spatiotemporally structured spontaneous behavior that, in simulations, supports efficient exploration of environments in the absence of explicit sensory cues.