Biology subjects

Douglass, A. D.

Publications and source records attributed to Douglass, A. D..

4 recordsLinked to original sources

bioRxiv2020

Hypothalamic dopamine neurons control sensorimotor behavior by modulating brainstem premotor nuclei

Dopamine (DA)-producing neurons are critically involved in the production of motor behaviors in multiple circuits that are conserved from basal vertebrates to mammals. While there is increasing evidence that DA neurons in the hypothalamus play a locomotor role, their precise contributions to behavior and the circuit mechanisms by which they are achieved remain unclear. Here we demonstrate that tyrosine hydroxylase 2-expressing (th2+) DA neurons in the zebrafish hypothalamus fire phasic bursts of activity to acutely promote swimming and modulate audiomotor behaviors on fast timescales. Their anatomy and physiology reveal two distinct functional DA modules within the hypothalamus. The first comprises an interconnected set of cerebrospinal fluid-contacting DA nuclei surrounding the third ventricle, which lack distal projections outside of the hypothalamus and influence locomotion through unknown means. The second includes neurons in the preoptic nucleus, which send long-range projections to targets throughout the brain, including the mid- and hindbrain, where they activate premotor circuits involved in swimming and sensorimotor integration. These data suggest a broad regulation of motor behavior by DA neurons within multiple hypothalamic nuclei and elucidate a novel functional mechanism for the preoptic DA neurons in the initiation of movement.

neuroscience↗

bioRxiv2020

Regenerated Interneurons Integrate Into Locomotor Circuitry Following Spinal Cord Injury

Whereas humans and other adult mammals lack the ability to regain locomotor function after spinal cord injury, zebrafish are able to recover swimming behavior even after complete spinal cord transection. We have previously shown that zebrafish larvae regenerate lost neurons within 9 days post-injury (dpi), but the functional contribution of these neurons to motor recovery is unknown. Here we show that multiple interneuron subtypes known to play a role in locomotor circuitry are regenerated in injured spinal cord segments during the period of functional recovery. Further, we show that one subtype of newly-generated interneurons receives excitatory input and fires synchronously with motor output by 9 dpi. Taken together, our data show that regenerative neurogenesis in the zebrafish spinal cord produces interneurons with the physiological capacity to participate in the recovery of locomotor function.

neuroscience↗

bioRxiv2018

Establishment of the miniature fish species Danionella translucida as a genetically and optically tractable neuroscience model

Integrative studies of the diverse neuronal networks that govern social behavior are hindered by the lack of methods to record neural activity comprehensively across the entire brain. The recent development of the miniature fish Danionella cerebrum as a model organism offers one potential solution, as the small size and optical transparency of these animals makes it possible to visualize circuit activity throughout the nervous system1-4. Here, we establish the feasibility of using Danionella as a model for social behavior and socially reinforced learning by showing that adult fish exhibit strong affiliative tendencies, and that social interactions can serve as the reinforcer in an appetitive conditioning paradigm. Fish exhibited an acute ability to identify conspecifics and distinguish them from closely related species, which was mediated by both visual and particularly olfactory cues. These behaviors were abolished by pharmacological and genetic interference with oxytocin signaling, demonstrating the conservation of key neural mechanisms observed in other vertebrates5-11. Our work validates Danionella as a tool for understanding the social brain in general, and its modulation by neuropeptide signaling in particular.

neuroscience↗

bioRxiv2017

Gaze-stabilizing central vestibular neurons project asymmetrically to extraocular motoneuron pools

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations -- such as asymmetric connectivity -- to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically-defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concor-dantly, when the entire population of asymmetrically-projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically-projecting central population thus participates in both up and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially-projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze-stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically-relevant stimuli without compromising reflexive behavior.\n\nSignificance StatementInterneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically-defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally we found that loss of these interneurons impairs a vital behavior, swim bladder inflation, that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior.

neuroscience↗