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Borba, C.

Publications and source records attributed to Borba, C..

6 recordsLinked to original sources

Notch expression during ctenophore development gives insight into its ancestral function

The canonical Notch pathway is a juxtacrine signaling module with widely conserved roles maintaining progenitor cell populations, promoting binary cell fate decisions, and establishing tissue boundaries. This pathway emerged in Metazoan lineages, although many molecular components and regulators existed prior to that divergence. Given that the vast majority of Notch studies focus on bilaterians, it is unclear when or how Notch gained its developmental signaling functions. To clarify the ancestral function of Notch, we turned to an early branching Metazoan -- the ctenophore Mnemiopsis leidyi -- and conducted structural analyses of putative Notch components to evaluate predicted signaling potential. We characterized gene expression of these components with in situ hybridization and show they are expressed during late embryogenesis. Using hybridization chain reaction (HCRTM), we examine MlNotch expression relative to canonical transcriptional targets and putative stem cell markers and identify differential expression patterns at a cellular resolution. Pharmacological inhibition reveals zones of active and inactive MlNotch during late embryonic development. Our results suggest that Notch evolved its signaling potential by the Metazoan divergence and is likely involved in regulating progenitor cell populations and coordinating developmental fate decisions.

developmental biology↗

An single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona

Ciona larvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain of Ciona has a previously uncharacterized single slow-oscillating inhibitory neuron (neuron cor-assBVIN78) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as the photoreceptor relay neurons. The anatomical location, gene expression and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, but which occur in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally-oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims, but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low level inputs while restricting them temporally to the troughs in inhibition.

neuroscience↗

A whole nervous system atlas of glutamate receptors reveals distinct receptor roles in sensorimotor circuits

A goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordate Ciona are well-suited to make contributions in this area. The small size of the Ciona larval nervous system ([~]180 neurons) has facilitated the full characterization of a connectome. In addition, the larvae display a range of behaviors that are readily quantified in both normal and manipulated larvae. Moreover, the small number of neurons allows for a neuron-by-neuron characterization of attributes such as neurotransmitter use. We present here a nervous system-wide atlas of glutamate receptor expression. Included in the atlas are both ionotropic receptors (AMPA, NMDA, and Kainate), and metabotropic receptors. The expression of these receptors is presented in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The expression of AMPA and NMDA receptors, in particular, helps to resolve the apparently paradoxical coproduction of GABA and glutamate by some photoreceptors. We find that the targets of these photoreceptors, midbrain relay neurons, primarily express NMDA receptors in the absence of AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a behavioral response (swimming) through a disinhibition mechanism. We hypothesize that NMDA receptors have a modulatory effect in the relay neurons. Other findings reported here are more unexpected. For example, the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets.

neuroscience↗

Automatic Detection and Neurotransmitter Prediction of Synapses in Electron Microscopy

This paper presents a deep-learning based workflow to detect synapses and predict their neurotransmitter type in the primitive chordate Ciona intestinalis (Ciona) EM images. Identifying synapses from electron microscopy (EM) images to build a full map of connections between neurons is a labor-intensive process and requires significant domain expertise. Automation of synapse detection and classification would hasten the generation and analysis of connectomes. Furthermore, inferences concerning neuron type and function from synapse features are in many cases difficult to make. Finding the connection between synapse structure and function is an important step in fully understanding a connectome. Activation maps derived from the convolutional neural network provide insights on important features of synapses based on cell type and function. The main contribution of this work is in the differentiation of synapses by neurotransmitter type through the structural information in their EM images. This enables prediction of neurotransmitter types for neurons in Ciona which were previously unknown. The prediction model with code is available on Github.

neuroscience↗

Deep origins for the tectal visual processing centers in chordates

Visual processing transforms the complex visual world into useful information. Ciona, a close relative of vertebrates, has one of the simplest nervous systems known, yet has a range of visuomotor behaviors. Among them are negative phototaxis and a looming-shadow response. These two behaviors are mediated by separate photoreceptor groups acting via distinct, but overlapping, neural circuits. We show here that processing circuits underlying both behaviors transform visual inputs to generate fold-change detection (FCD) outputs. In FCD, the response scales with the relative fold changes in input, but is invariant to the overall magnitude of the stimulus. Several different circuit architectures can generate FCD responses. Both the behavioral outputs and the putative circuitry for the two visuomotor behaviors point to them using different FCD circuits. Pharmacological treatment points to circuits in the posterior brain vesicle of Ciona, a region we speculate shares homology with the vertebrate midbrain, as important for FCD.

neuroscience↗

Parallel Visual Circuitry in a Basal Chordate

A common CNS architecture is observed in all chordates, from vertebrates to basal chordates like the ascidian Ciona. Currently Ciona stands apart among chordates in having a complete larval CNS connectome. Starting with visuomotor circuits predicted by the Ciona connectome, we used expression maps of neurotransmitter use with behavioral assays and pharmacology to identify two parallel visuomotor circuits that are responsive to different components of visual stimuli. The first circuit is characterized by glutamatergic photoreceptors and responds to the direction of light. These photoreceptors project to cholinergic motor neurons, via two tiers of cholinergic interneurons. The second circuit is responsive to changes in ambient light and mediates an escape response. This circuit starts with novel GABAergic photoreceptors which project to GABAergic interneurons, and then to cholinergic interneurons shared with the first circuit. Our observations on neurotransmitter use and the behavior of larvae lacking photoreceptors indicate the second circuit is disinhibitory.

neuroscience↗