Biology subjects

Ostrovsky, A. D.

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

3 recordsLinked to original sources

bioRxiv2024

Characterisation of transgenic lines labelling reticulospinal neurons in larval zebrafish

From lamprey to monkeys, the organization of the descending control of locomotion is conserved across vertebrates. Reticulospinal neurons (RSNs) form a bottleneck for descending commands, receiving innervation from diencephalic and mesencephalic locomotor centres and providing locomotor drive to spinal motor circuits. Given their optical accessibility in early development, larval zebrafish offer a unique opportunity to study reticulospinal circuitry. In fish, RSNs are few, highly stereotyped, uniquely identifiable, large neurons spanning from the midbrain to the medulla. Classically labelled by tracer dye injections into the spinal cord, recent advances in genetic tools have facilitated the targeted expression of transgenes in diverse brainstem neurons of larval zebrafish. Here, we provide a comparative characterization of four existing and three newly established transgenic lines in larval zebrafish. We determine which identified neurons are consistently labelled and offer projection-specific genetic access to subpopulations of RSNs. We showcase transgenic lines that label most or all RSNs (nefma, adcyap1bccu96Et) or subsets of RSNs, including ipsilateral (vsx2, calcaccu75Et), contralateral (pcp4accu97Tg) or all (tiam2ay264Et) components of the Mauthner array, or midbrain-only RSNs (s1171tEt). In addition to RSNs, selected transgenic lines (nefma, s1171tEt, calcaccu75Et) labelled other potential neurons of interest in the brainstem. For those, we performed in situ hybridisation to show expression patterns of several excitatory and inhibitory neurotransmitters at larval stages as well as glutamatergic expression patterns in juvenile fish. We provide an overview of transgene expression in the brainstem of larval zebrafish that serves to lay a foundation for future studies in the supraspinal control of locomotion. Significance StatementGenetic access to subpopulations of brainstem neurons greatly facilitates the dissection of supraspinal circuitry and function. Here, we present several new transgenic lines and rigorously describe existing ones, all in terms of their degree of overlap with the reticulospinal system, variability in transgenic labelling and neurotransmitter identity. Having transgenic access to different subpopulations of reticulospinal neurons enables targeted functional calcium imaging, anatomical tracing and optogenetic manipulations to decipher the role of individual reticulospinal neurons in movement production, ultimately clarifying existing understanding and facilitating future studies in the supraspinal control of locomotion. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/629714v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@d2161eorg.highwire.dtl.DTLVardef@aa4b97org.highwire.dtl.DTLVardef@48c9b9org.highwire.dtl.DTLVardef@b394ee_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Dimensionality reduction reveals separate translation and rotation populations in the zebrafish hindbrain

In many brain areas, neuronal activity is associated with a variety of behavioral and environmental variables. In particular, neuronal responses in the zebrafish hindbrain relate to oculomotor and swimming variables, as well as sensory information. However, the precise functional organization of the neurons has been difficult to unravel since neuronal responses are heterogeneous. Here we used dimensionality reduction methods on neuronal population data to reveal the role of the hindbrain in visually-driven oculomotor behavior and swimming. We imaged neuronal activity in zebrafish expressing GCaMP6s in the nucleus of almost all neurons, while monitoring the behavioral response to gratings that rotated with different speeds. We then used reduced-rank regression, a method that condenses the sensory and motor variables into a smaller number of features, to predict the fluorescence traces of all ROIs (regions of interest). Despite the potential complexity of the visuo-motor transformation, our analysis revealed that the bulk of population activity can be explained by only two features. Based on the contribution of these features to each ROIs activity, ROIs formed three clusters. One cluster was related to vergent movements and swimming, whereas the other two clusters related to leftward and rightward rotation. Voxels corresponding to these clusters were segregated anatomically, with leftward and rightward rotation clusters located selectively to the left and right hemispheres, respectively. Just as described in many cortical areas, our analysis revealed that single neuron complexity co-exists with a simpler population-level description, thereby providing insights into the organization of visuo-motor transformations in the hindbrain.

neuroscience↗

bioRxiv2019

Motor circuit function is stabilized during postembryonic growth by anterograde trans-synaptic Jelly Belly - Anaplastic Lymphoma Kinase signaling

The brain adapts to a changing environment or growing body size by structural growth and synaptic plasticity. Mechanisms studied to date promote synaptic growth between partner neurons, while negative counterparts that inhibit such interactions have so far remained elusive. Here, we investigate the role of Jeb-Alk signaling in coordinating motor circuit growth during larval stages of Drosophila. We quantify neuronal growth dynamics by intra-vital imaging, and synaptogenesis at nanometer resolution using endogenously labeled synaptic proteins, conditionally tagged with a fluorophore, and link changes in circuit anatomy with altered synaptic physiology and behavior. We find that loss of Jeb-Alk signaling leads to increased strengthening of synaptic excitation by developmental addition of additional postsynaptic but not pre-synaptic specializations. These changes ultimately lead to an epilepsy-like seizure behavior. We thus demonstrate that trans-synaptic anterograde Jeb-Alk signaling acts to stabilize developmental plasticity and circuit function, and that it does so specifically during postembryonic growth.

neuroscience↗