Brain-wide Organization of Neuronal Activity and Convergent Sensorimotor Transformations in Larval Zebrafish

Abstract

Summary Simultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental approaches often focus on singular behavioral paradigms or brain areas. Here, we recorded whole-brain neuronal activity of larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. We identified neurons tuned to each stimulus type and motor output, and discovered groups of neurons in the anterior hindbrain that respond to different stimuli that elicit similar behavioral responses. These convergent sensorimotor representations were only weakly correlated to instantaneous motor activity, suggesting that they critically inform, but do not directly generate, behavioral choices. To catalog brain-wide activity beyond explicit sensorimotor processing, we developed an unsupervised clustering technique that organizes neurons into functional groups. These analyses enabled a broad overview of the functional organization of the brain, and revealed numerous brain nuclei whose neurons exhibit concerted activity patterns.

Brain-wide visual habituation networks in wild type and fmr1 zebrafish

“…When looming stimuli are presented to larval zebrafish, visual information converges in the tectum, where local circuits are proposed to calculate the imminence of a threat [31][32][33] . However, additional structures respond to looms [31][32][33][34][35] , and others, including the hypothalamus, modulate the visual escape behavior in contexts other than habituation 34,36,37 . The result is an intriguing but sketchy outline of the habituation network, and in the absence of a whole-brain cellular-resolution analysis, numerous questions about this behaviorally important process remain unanswered.Addressing these questions is especially important because of the role that sensorimotor transformations and habituation play in psychiatric disorders including schizophrenia, autism spectrum disorder (ASD), and Fragile X syndrome (FXS) 38 .…”

Functional Genomics of Epilepsy and Associated Neurodevelopmental Disorders Using Simple Animal Models: From Genes, Molecules to Brain Networks

“…Various genetic lines of pigment deficient larval zebrafish have been developed which enable unrestricted optical access into the developing brain (Antinucci and Hindges, 2016). Furthermore, the development of various transgenic reporters of cellular activity, such as GCaMP and RGECO enable the imaging of calcium dynamics in single cells and whole brain networks during behavior, using fluorescence microscopy (Figure 2; Walker et al, 2013;Wolf et al, 2017;Chen et al, 2018). In fact, various transgenic lines have also been developed to monitor specifically GABA (Marvin et al, 2019) or glutamate (Marvin et al, 2013) signaling in vivo.…”

Model-based decoupling of evoked and spontaneous neural activity in calcium imaging data

“…We characterised the stimulus-driven component of the population activity by simply expressing each fluorescence trace as a linear combination of regressors that specify the basic shape and timescale of calcium activity. We defined a basis of stimulus regressors [17,18] by convolving a calcium impulse response kernel with the presentation times of each stimulus and performed a multivariate linear regression of the population data onto this basis set using non-negative least squares (Figure 1c). Any highly structured activity in the residual data would likely be driven primarily by latent sources of SA not directly related to the onset of the presented stimuli.…”