bioRxiv Subject Collection: Neuroscience's Journal
 
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Friday, December 6th, 2024

    Time Event
    12:20a
    Synapse profiling of identified neurons in the Drosophila brain
    Synapses are highly heterogeneous even within a single motor neuron in Drosophila melanogaster. In the central nervous system (CNS), the degree of stereotypy in the synaptic structure of specific neurons across individuals remains largely unexplored, due to the significant effort required to analyze multiple brain samples. Utilizing the split-GFP fluorescence-tagging, we achieved endogenous labeling of the presynaptic active zone (AZ) scaffold protein Bruchpilot (Brp) in a cell-type-specific manner. This strategy allowed us to devise a high-throughput quantification pipeline to characterize and compare cell-type-specific AZ structures across individuals. We found that multiple structural parameters such as Brp localization and AZ size revealed significant intracellular synaptic heterogeneity and cell-type-dependent stereotypy in the mushroom body (MB) circuit. Furthermore, we found that the AZ organization can be surprisingly local, even at the neighboring AZ level. These findings therefore suggest multi-level organizations of AZs, from neighboring synapses to across individuals.

    TeaserState-of-art fluorescence-based imaging technique and high-throughput analysis revealed previously unidentified synaptic organizations.
    12:20a
    Octopamine signals coordinate the spatial pattern of presynaptic machineries in the Drosophila mushroom bodies
    Neurons possess numerous synaptic terminals. Presynaptic structures in a single motor neuron exhibit heterogeneity that associated with distinct characters of synaptic vesicle release. However, such heterogeneity is scarcely reported in the central nervous system, and its regulatory mechanism remain unknown. Here, we explored the intracellular diversity of presynaptic structures within the Kenyon cells of the Drosophila mushroom bodies. Applying the CRISPR/Cas9-mediated split-GFP tagging, we devised cell-type specific fluorescent labeling of the endogenous active zone scaffold protein, Bruchpilot (Brp). Morphometry of individual Brp clusters revealed heterogenous accumulations among the axon terminal compartments. Mechanistically, the localized octopaminergic signaling along Kenyon cell terminals regulate the Brp heterogeneity via Oct{beta}2R and cAMP signaling. We further found that acute food deprivation reduced the compartmental heterogeneity of Brp accumulation in an octopaminergic signaling-dependent manner. These findings are consistent with the mushroom body functions in integrating the signals of changing physiological states.
    8:36p
    Voluntary action sharpens sensory prediction and facilitates neural processing of contingent sensory stimuli
    Self- and externally generated sensations differ in sensory responses and motor preparation. However, mechanistic evidence linking the two is scarce. Here, participants made active (self-initiated) or passive (finger moved by electromagnet) movements that triggered a bimodal auditory/visual stimulus. These were followed, in a block-wise manner, by a unimodal auditory/visual comparison stimulus, and participants judged which stimulus was brighter or louder. Motor preparation ERPs encoded task modality and movement, while sensory ERPs showed reduced task differences for active, demonstrating sensory suppression. Next, we decoded task modality within active and passive. During motor preparation, the active condition showed higher accuracy, reflecting enhanced predictive processes. In the sensory perception period, accuracy was higher in the passive condition, mirroring previous reports of reduced sensory responses to self-generated stimuli. Temporal generalisation showed pattern similarities in the alpha band amplitude between the motor preparation and the stimulus perception windows. This suggests that alpha oscillations may encode sensory predictions generated during motor preparation. Our findings provide mechanistic evidence of action-effect prediction during voluntary actions.
    8:36p
    Phase-specific premotor inhibition modulates leech rhythmic motor output
    Understanding how motoneuron activity is finely tuned remains an open question. Leeches are a highly suitable organism for studying motor control due to their well-characterized behaviors and relatively simple nervous system. On solid surfaces leeches display crawling, a rhythmic motor pattern that can be elicited in the isolated nerve cord or even in ganglia isolated from it. This study aimed to learn how this motor output is shaped by concurrent premotor signals. Specifically, we analyzed how electrophysiological manipulation of a premotor nonspiking (NS) neuron, that forms a recurrent inhibitory circuit (homologous to vertebrate Renshaw cells), shapes the leech crawling motor pattern. The study included a quantitative analysis of motor units active throughout the fictive crawling cycle that shows that the rhythmic motor output in isolated ganglia mirrors the phase relationships observed in vivo. Taken together, the study reveals that the premotor NS neurons, under the control of the segmental pattern generator, modulated the degree of excitation of motoneurons during crawling in a phase-specific manner.
    11:17p
    Between-movie variability severely limits generalizability of "naturalistic" neuroimaging
    "Naturalistic imaging" paradigms, where participants watch movies during fMRI, have gained popularity over the past two decades. Many movie-watching studies measure inter-subject correlation (ISC), which refers to the correlation between participants' neural activation time series. Previous research has focused on explaining ISC differences during movie-watching based on individual states and traits, such as social distance, personality, and political orientation. For example, friends show higher ISC than strangers while watching movies. However, movies are not natural categories but cultural artifacts that evoke varying levels of ISC depending on content, directing style, or editing methods. This raises questions about how much trait- or state-like differences in ISC depend on the specific movies chosen, potentially limiting the generalizability of findings across different movies. Here, we used an fMRI dataset of 112 participants watching eight animated movies to (a) quantify between-movie variability in ISC across the brain and (b) assess the implications for the generalizability of trait- or state-like effects on ISC. We found substantial between-movie variability in ISC, with this variability differing across brain regions. Crucially, brain regions with the highest ISC exhibited the greatest variability, indicating that trait- or state-like differences in ISC from one movie may not generalize to others. We conclude that variability between movies limits the generalizability of trait- or state-like ISC differences. Using a specific movie in neuroscience should be treated similarly to using a particular task, requiring a comparable characterization of the constituent cognitive elements. Broad generalizations about "naturalistic imaging" or "movie watching" are not warranted.

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