Biology subjects

Deats, S. P.

Publications and source records attributed to Deats, S. P..

3 recordsLinked to original sources

bioRxiv2026

APOE is a presynaptic protein that accumulates with age and modulates neurotransmitter release

The synaptic vesicle (SV) cycle is the fastest membrane trafficking and protein sorting process in biology. It underlies neuronal communication and cognition, yet synaptic function declines during normal aging, increasing vulnerability to neurologic disease. How the SV cycle is maintained across the lifespan of a complex organism remains unclear. Here, we used wild-type mice (C57BL/6J) to define the age- and sex-stratified molecular landscape of SVs and identified apolipoprotein E (APOE) as an abundant presynaptic protein further enriched in aged female samples. Super-resolution imaging, cell-type selective expression, and protease protection assays demonstrate that APOE originates from astroglia and associates with the cytosolic face of SVs. Using iGluSnFR and pHluorin optophysiology, we find that both decreased and increased APOE levels impair neurotransmission during stimulus trains. Together, these findings place APOE at the synapse and establish it as a cell-nonautonomous regulator of the SV cycle.

neuroscience↗

bioRxiv2019

Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity

Drugs of abuse induce neuroadaptations, including synaptic plasticity, that are critical for transition to addiction, and genes and pathways that regulate these neuroadaptations are potential therapeutic targets. Tropomodulin 2 (Tmod2) is an actin-regulating gene that plays an important role in synapse maturation and dendritic arborization and has been implicated in substance-abuse and intellectual disability in humans. Here we mine the KOMP2 data and find that Tmod2 knockout mice show emotionality phenotypes that are predictive of addiction vulnerability. Detailed addiction phenotyping showed that Tmod2 deletion does not affect the acute locomotor response to cocaine administration. However, sensitized locomotor responses are highly attenuated in these knockouts, indicating perturbed drug-induced plasticity. In addition, Tmod2 mutant animals do not self-administer cocaine indicating lack of hedonic responses to cocaine. Whole brain MR imaging shows differences in brain volume across multiple regions although transcriptomic experiments did not reveal perturbations in gene co-expression networks. Detailed electrophysiological characterization of Tmod2 KO neurons, showed increased spontaneous firing rate of early postnatal and adult cortical and striatal neurons. Cocaine-induced synaptic plasticity that is critical for sensitization is either missing or reciprocal in Tmod2 KO nucleus accumbens shell medium spiny neurons, providing a mechanistic explanation of the cocaine response phenotypes. Combined, these data provide compelling evidence that Tmod2 is a major regulator of plasticity in the mesolimbic system and regulates the reinforcing and addictive properties of cocaine.\n\nSignificance statementWe identify, characterize, and establish tropomodulin 2 (Tmod2), an actin-regulating gene exclusively expressed in neurons, as an important regulator of addiction-related phenotypes. We show that Tmod2, knockout mice (Tmod2 KO) exhibit phenotypes that are predictive of addiction. In detailed addiction phenotyping, we find the Tmod2 regulates cocaine sensitization and self-administration. We explore anatomical, transcriptional, electrophysiological mechanisms of this regulation. Combined these studies provide compelling evidence that Tmod2 is critical for synaptic plasticity necessary for transition to addiction.

neuroscience↗

bioRxiv2018

Robust Mouse Tracking in Complex Environments using Neural Networks

The ability to track animals accurately is critical for behavioral experiments. For video-based assays, this is often accomplished by manipulating environmental conditions to increase contrast between the animal and the background, in order to achieve proper foreground/background detection (segmentation). However, as behavioral paradigms become more sophisticated with ethologically relevant environments, the approach of modifying environmental conditions offers diminishing returns, particularly for scalable experiments. Currently, there is a need for methods to monitor behaviors over long periods of time, under dynamic environmental conditions, and in animals that are genetically and behaviorally heterogeneous. To address this need, we developed a state-of-the-art neural network-based tracker for mice, using modern machine vision techniques. We test three different neural network architectures to determine their performance on genetically diverse mice under varying environmental conditions. We find that an encoder-decoder segmentation neural network achieves high accuracy and speed with minimal training data. Furthermore, we provide a labeling interface, labeled training data, tuned hyperparameters, and a pre-trained network for the mouse behavior and neuroscience communities. This general-purpose neural network tracker can be easily extended to other experimental paradigms and even to other animals, through transfer learning, thus providing a robust, generalizable solution for biobehavioral research.

animal behavior and cognition↗