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Benedict, J.

Publications and source records attributed to Benedict, J..

4 recordsLinked to original sources

Molecular and ultrastructural characterization of the intramuscular nerve cords of the octopus arm

Cephalopod arms are controlled by a distributed peripheral nervous system comprising the axial nerve cord (ANC), subacetabular ganglia associated with each sucker, four longitudinal intramuscular nerve cords (INCs) embedded within the arm musculature and oblique connectives (OCs) running between INCs. Despite their prominent anatomical position and proposed roles in local sensorimotor integration and inter-arm coordination, the INCs remain poorly characterized with respect to cell-type composition and molecular identity. Here, we report the first integrative characterization of INC structure and composition in Octopus bocki by combining serial block-face scanning electron microscopy (SBEM) with multiplexed hybridization chain reaction (HCR) in situ labeling. We show that oral and aboral INCs share a consistent internal organization comprising distinct cell body regions, a peripheral tract layer, and a central synaptic zone. Both oral and aboral cords contain morphologically diverse cell populations, including abundant bipolar neurons with long unbranched processes and a second class of neurons with highly branched processes bearing bouton-like enlargements. On the molecular level, the sampled INCs are enriched for glutamatergic and buccalin-positive cells, and express abundant glia-associated transcripts. In contrast to the ANC, cholinergic, dopaminergic, serotonergic, and octopaminergic markers were not detected above background. We also characterize the relationship between the INCs and adjacent oblique connectives (OCs), showing that these structures run in close proximity but remain physically separate within the sampled high-resolution volume, with no shared fibers or crossing processes detected across the observed boundary. Together, these data establish a cellular and molecular framework for the INCs and clarify their relationship to neighboring peripheral pathways.

neuroscience↗

The lateral habenula is required for maternal behavior in the mouse dam

Mammalian parenting is an unusually demanding commitment. How did evolution co-opt the reward system to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams towards their biological pups. Next, we demonstrate that through chronic chemogenetic inactivation of the LHb using DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercepts model suggesting LHb-inactivation prevents the acquisition of the novel pup retrieval maternal behavior and decreases nest building performance, an already-established behavior, in primiparous mouse dams. Lastly, we examine the spatial histology of kainic-acid treated dams with a random intercepts model, which suggests that the role of LHb in maternal behavior may be preferentially localized at the posterior aspect of this structure. Together, these findings serve to establish the LHb as required for maternal behavior in the mouse dam, thereby complementing previous findings implicating the LHb in parental behavior using pup-sensitized virgin female mice. Significance StatementWork conducted using rats in the 1990s suggested an important role for the LHb in maternal behavior, but this area of research has since lain dormant. In the interim, the LHb has been garnering attention as a hub for punishment signaling. Recently, interest in the LHbs role in maternal behavior was renewed, with an important paper examining LHb function during pup-directed behaviors in pup-sensitized virgin female mice. But it is unknown how closely pup-directed behaviors in sensitized virgin females may mimic maternal behavior in natural mouse mothers. This work demonstrates the importance of the LHb in the regulation of natural maternal behavior in the mouse.

neuroscience↗

PiE: An open source pipeline for home cage behavioral analysis.

Over the last two decades a growing number of neuroscience labs are conducting behavioral assays in rodents. The equipment used to collect this behavioral data must effectively limit environmental and experimenter disruptions, to avoid confounding behavior data. Proprietary behavior boxes are expensive, offer limited compatible sensors, and constrain analysis with closed-source hardware and software. Here, we introduce PiE, an open-source, end-to-end, user-configurable, scalable, and inexpensive behavior assay system. The PiE system includes the custom-built behavior box to hold a home cage, as well as software enabling continuous video recording and individual behavior box environmental control. To limit experimental disruptions, the PiE system allows the control and monitoring of all aspects of a behavioral experiment using a remote web browser, including real-time video feeds. To allow experiments to scale up, the PiE system provides a web interface where any number of boxes can be controlled, and video data easily synchronized to a remote location. For the scoring of behavior video data, the PiE system includes a standalone desktop application that streamlines the blinded manual scoring of large datasets with a focus on quality control and assay flexibility. The PiE system is ideal for all types of behavior assays in which video is recorded. Users are free to use individual components of this setup independently, or to use the entire pipeline from data collection to analysis. Alpha testers have included scientists without prior coding experience. An example pipeline is demonstrated with the PiE system enabling the user to record home cage maternal behavior assays, synchronize the resulting data, conduct blinded scoring, and import the data into R for data visualization and analysis.

neuroscience↗

STEP inhibition prevents Aβ mediated damage in dendritic complexity and spine density in Alzheimers disease.

Loss of dendritic spines and decline of cognitive function are hallmarks of patients with Alzheimers disease (AD). Previous studies have shown that AD pathophysiology involves increased expression of a central nervous system-enriched protein tyrosine phosphatase called STEP (STriatal-Enriched protein tyrosine Phosphatase). STEP opposes the development of synaptic strengthening by dephosphorylating substrates, including GluN2B, Pyk2 and ERK1/2. Genetic reduction of STEP as well as pharmacological inhibition of STEP improves cognitive function and hippocampal memory in the 3xTg AD mouse model. Here, we show that the improved cognitive function is accompanied by an increase in synaptic connectivity in cell cultures as well as in the triple transgenic AD mouse model, further highlighting the potential of STEP inhibitors as a therapeutic agent.

neuroscience↗