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Johnson Lab / Publications
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6 Publications

Showing 1-6 of 6 results
01/06/20 | Probabilistic Models of Larval Zebrafish Behavior Reveal Structure on Many Scales
Robert Evan Johnson , Scott Linderman , Thomas Panier , Caroline Lei Wee , Erin Song , Kristian Joseph Herrera , Andrew Miller , Florian Engert
Current Biology. 01/2020;30:70 - 82.e4. doi:

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout types emitted over time. We then construct probabilistic models—specifically, marked renewal processes—to evaluate how bout types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.

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10/18/19 | A bidirectional network for appetite control in larval zebrafish.
Wee CL, Song EY, Johnson RE, Ailani D, Randlett O, Kim J, Nikitchenko M, Bahl A, Yang C, Ahrens MB, Kawakami K, Engert F, Kunes S
Elife. 2019 Oct 18;8:. doi: 10.7554/eLife.43775

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

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12/03/18 | Point process latent variable models of larval zebrafish behavior
Anuj Sharma , Robert Johnson , Florian Engert , Scott W. Linderman
NeurIPS. 12/2018:

A fundamental goal of systems neuroscience is to understand how neural activity gives rise to natural behavior. In order to achieve this goal, we must first build comprehensive models that offer quantitative descriptions of behavior. We develop a new class of probabilistic models to tackle this challenge in the study of larval zebrafish, an important model organism for neuroscience. Larval zebrafish locomote via sequences of punctate swim bouts--brief flicks of the tail--which are naturally modeled as a marked point process. However, these sequences of swim bouts belie a set of discrete and continuous internal states, latent variables that are not captured by standard point process models. We incorporate these variables as latent marks of a point process and explore various models for their dynamics. To infer the latent variables and fit the parameters of this model, we develop an amortized variational inference algorithm that targets the collapsed posterior distribution, analytically marginalizing out the discrete latent variables. With a dataset of over 120,000 swim bouts, we show that our models reveal interpretable discrete classes of swim bouts and continuous internal states like hunger that modulate their dynamics. These models are a major step toward understanding the natural behavioral program of the larval zebrafish and, ultimately, its neural underpinnings.

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10/17/13 | Homeostatic plasticity shapes the visual system’s first synapse
Johnson RE, Tien N, Shen N, Pearson JT, Soto F, Kerschensteiner D
Nature Communications. 10/2017;8(1):. doi: 10.1038/s41467-017-01332-7

Vision in dim light depends on synapses between rods and rod bipolar cells (RBCs). Here, we find that these synapses exist in multiple configurations, in which single release sites of rods are apposed by one to three postsynaptic densities (PSDs). Single RBCs often form multiple PSDs with one rod; and neighboring RBCs share ~13% of their inputs. Rod-RBC synapses develop while ~7% of RBCs undergo programmed cell death (PCD). Although PCD is common throughout the nervous system, its influences on circuit development and function are not well understood. We generate mice in which ~53 and ~93% of RBCs, respectively, are removed during development. In these mice, dendrites of the remaining RBCs expand in graded fashion independent of light-evoked input. As RBC dendrites expand, they form fewer multi-PSD contacts with rods. Electrophysiological recordings indicate that this homeostatic co-regulation of neurite and synapse development preserves retinal function in dim light.

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01/10/14 | Retrograde Plasticity and Differential Competition of Bipolar Cell Dendrites and Axons in the Developing Retina
Johnson R, Kerschensteiner D
Current Biology. Jan/2014;24(19):2301 - 2306. doi: 10.1016/j.cub.2014.08.018

Most neurons function in the context of pathways that process and propagate information through a series of stages, e.g., from the sensory periphery to cerebral cortex. Because activity at each stage of a neural pathway depends on connectivity at the preceding one, we hypothesized that during development, axonal output of a neuron may regulate synaptic development of its dendrites (i.e., retrograde plasticity). Within pathways, neurons often receive input from multiple partners and provide output to targets shared with other neurons (i.e., convergence). Converging axons can intermingle or occupy separate territories on target dendrites. Activity-dependent competition has been shown to bias target innervation by overlapping axons in several systems. By contrast, whether territorial axons or dendrites compete for targets and inputs, respectively, has not been tested. Here, we generate transgenic mice in which glutamate release from specific sets of retinal bipolar cells (BCs) is suppressed. We find that dendrites of silenced BCs recruit fewer inputs when their neighbors are active and that dendrites of active BCs recruit more inputs when their neighbors are silenced than either active or silenced BCs with equal neighbors. By contrast, axons of silenced BCs form fewer synapses with their targets, irrespective of the activity of their neighbors. These findings reveal that retrograde plasticity guides BC dendritic development in vivo and demonstrate that dendrites, but not territorial axons, in a convergent neural pathway engage in activity-dependent competition. We propose that at a population level, retrograde plasticity serves to maximize functional representation of inputs.

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07/17/13 | NGL-2 Regulates Pathway-Specific Neurite Growth and Lamination, Synapse Formation, and Signal Transmission in the Retina
Soto F, Watkins KL, Johnson RE, Schottler F, Kerschensteiner D
Journal of Neuroscience. May-07-2014;33(29):11949 - 11959. doi: 10.1523/JNEUROSCI.1521-13.2013

Parallel processing is an organizing principle of many neural circuits. In the retina, parallel neuronal pathways process signals from rod and cone photoreceptors and support vision over a wide range of light levels. Toward this end, rods and cones form triad synapses with dendrites of distinct bipolar cell types, and the axons or dendrites, respectively, of horizontal cells (HCs). The molecular cues that promote the formation of specific neuronal pathways remain largely unknown. Here, we discover that developing and mature HCs express the leucine-rich repeat (LRR)-containing protein netrin-G ligand 2 (NGL-2). NGL-2 localizes selectively to the tips of HC axons, which form reciprocal connections with rods. In mice with null mutations in Ngl-2 (Ngl-2⁻/⁻), many branches of HC axons fail to stratify in the outer plexiform layer (OPL) and invade the outer nuclear layer. In addition, HC axons expand lateral territories and increase coverage of the OPL, but establish fewer synapses with rods. NGL-2 can form transsynaptic adhesion complexes with netrin-G2, which we show to be expressed by photoreceptors. In Ngl-2⁻/⁻ mice, we find specific defects in the assembly of presynaptic ribbons in rods, indicating that reverse signaling of complexes involving NGL-2 regulates presynaptic maturation. The development of HC dendrites and triad synapses of cone photoreceptors proceeds normally in the absence of NGL-2 and in vivo electrophysiology reveals selective defects in rod-mediated signal transmission in Ngl-2⁻/⁻ mice. Thus, our results identify NGL-2 as a central component of pathway-specific development in the outer retina.

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