Katenka, N. | bioRxiv Science

bioRxiv2026

Aberrant Pain Phenotypes Emerge Following Prenatal Hypoxic-Ischemic Injury in a Rabbit Model of Cerebral Palsy

Cerebral Palsy (CP) is the most common motor disability in childhood, and the most frequent comorbidity is pain. Rabbit kits subjected to prenatal hypoxia-ischemia (HI) exhibit allodynia and an expansion of nociceptive afferents in the lumbar spinal cord at postnatal day (P5). In this study, we examined how HI alters the development of multiple sensory modalities and its effect on psychosocial measures and C-fiber distribution in the spinal cord. To do this, we performed an HI surgery to occlude blood flow to fetal New Zealand White rabbits for 40 minutes, or a sham surgery. We performed von Frey, Hargreaves, and a cold allodynia test at P1, P5, P11, and P18. Additionally, we performed open field, a two-texture preference test, and immunofluorescence assays at P18. HI kits exhibit altered development and allodynia in von Frey and Hargreaves and decreased sensitivity to cold. HI kits spend less time on the aversive side of the two-texture preference apparatus and more time in the center of an open field but a higher ratio of that time immobile. This is accompanied by changes in the distribution of C-fibers in the dorsal horn of the cervical and lumbar spinal cord. A principal components analysis revealed prenatal HI produces coordinated alterations across sensory and behavioral domains and multivariate phenotyping captures the overall HI phenotype more comprehensively than any single measure. Overall, HI rabbits kits exhibit altered sensory development, allodynia, anxiety-like behavior, and changes to the distribution of nociceptive afferents in the dorsal horn of the spinal cord.

neuroscience↗

bioRxiv2025

Machine-Learning Classification of Motor Unit Types in the Adult Mouse

The diversity of motor units arises from differences in the contractile properties of muscle fibers and the intrinsic electrical properties of their motoneurons. In mice, however, this relationship has not been quantitatively defined, and conventional classification often relies on subjective thresholds. Here, we combined in vivo intracellular recordings with supervised and unsupervised machine-learning methods to test whether motoneuron electrophysiology can predict the physiological identity of mouse motor units. Unbiased clustering identified four groups corresponding to slow (S), fast fatigue-resistant (FR), intermediate (FI), and fast fatigable (FF) types. A multinomial logistic regression model performed well, with most errors occurring between FI and FF types, which showed substantial overlap. Reducing the task to three classes improved accuracy. Feature selection revealed that four electrophysiological properties (input conductance, rheobase, AHP duration, maximal frequency) were sufficient for high predictive performance. Overall, this study provides a quantitative description of mouse motor-unit properties and a framework for incorporating motor-unit diversity into future investigations of neuromuscular physiology and disease.

neuroscience↗

bioRxiv2020

Inhibitory interneurons show early dysfunction in a SOD1 mouse model of ALS

Few studies in amyotrophic lateral sclerosis (ALS) measure effects of the disease on inhibitory interneurons synapsing onto motoneurons (MNs). However, inhibitory interneurons could contribute to dysfunction, particularly if altered before MN neuropathology, and establish a long-term imbalance of inhibition / excitation. We directly assessed excitability and morphology of glycinergic (GlyT2 expressing) ventral lumbar interneurons from SOD1G93AGlyT2eGFP (SOD1) and wildtype GlyT2eGFP (WT) mice on postnatal days 6-10. Patch clamp revealed dampened excitability in SOD1 interneurons, including depolarized persistent inward currents (PICs), increased voltage and current threshold for firing action potentials, along with a marginal decrease in afterhyperpolarization (AHP) duration. Primary neurites of ventral SOD1 inhibitory interneurons were larger in volume and surface area than WT. GlyT2 interneurons were then divided into 3 subgroups based on location: (1) interneurons within 100 m of the ventral white matter, where Renshaw cells (RCs) are located, (2) interneurons interspersed with MNs in lamina IX, and (3) interneurons in the intermediate ventral area including laminae VII and VIII. Ventral interneurons in the RC area were the most profoundly affected, exhibiting more depolarized PICs and larger primary neurites. Interneurons in lamina IX had depolarized PIC onset. In lamina VII-VIII, interneurons were least affected. In summary, inhibitory interneurons show very early region-specific perturbations poised to impact excitatory / inhibitory balance of MNs, modify motor output, and provide early biomarkers of ALS. Therapeutics like riluzole which universally reduce CNS excitability could exacerbate the inhibitory dysfunction described here. Abstract Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/348359v4_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1dde8beorg.highwire.dtl.DTLVardef@1db13edorg.highwire.dtl.DTLVardef@1f95cbeorg.highwire.dtl.DTLVardef@37ec18_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOAbstract Figure:C_FLOATNO SOD1 glycinergic interneurons in the ventral horn show altered morphology and excitability, including depolarization of PICs, depolarized threshold, shorter AHPs, smaller somata and larger primary neurites. Ventrally located interneurons are the most prominently affected. C_FIG Key Points SummaryO_LISpinal inhibitory interneurons could contribute to amyotrophic lateral sclerosis (ALS) pathology, but their excitability has never been directly measured. C_LIO_LIWe studied the excitability and morphology of glycinergic interneurons in early postnatal transgenic mice (SOD1G93AGlyT2eGFP). C_LIO_LIInterneurons were less excitable and had marginally smaller somas but larger primary neurites in SOD1 mice. C_LIO_LIGlyT2 interneurons were analyzed according to their localization within the ventral spinal cord. Interestingly, the greatest differences were observed in the most ventrally-located interneurons. C_LIO_LIWe conclude that inhibitory interneurons show presymptomatic changes that may contribute to excitatory / inhibitory imbalance in ALS. C_LI

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