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bioRxiv · 10.64898/2026.07.03.736384

Maternal behavioral compensation after neonatal separation fails to prevent spinal circuit reprogramming in offspring

Illouz, H.·Poli, A.·Brik, Y.·Lelievre, V.·Poisbeau, P.
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Abstract

Early-life adversity durably alters neural development through complex mother-offspring interactions whose underlying mechanisms remain poorly understood. We investigated how neonatal maternal separation (NMS) affects the large repertoire of maternal behaviors and subsequently influences spinal nociceptive circuit development and pain responses in rat offspring. Rat dams underwent NMS from postnatal day 2 (P2) to P12, 3h/day, and maternal behaviors were assessed before and after the separation period. These behaviors were compared to those of control (non-separated) dams. Offspring spinal cord and dorsal root ganglia were analyzed at P14 and P24 for several neurotrophic, glutamatergic, and GABAergic gene expression patterns. Offspring nociceptive sensitivity was also assessed at P24. NMS induced increased maternal behaviors (including longer arched-back nursing, higher nest occupancy, and better pup retrieval efficiency), alongside reduced self-care behaviors. These behavioral adaptations were correlated with spinal gene reprogramming in offspring, characterized by a biphasic developmental pattern. At P14, we observed elevated neurotrophic signaling alongside increased GABAergic and glutamatergic markers. By P24, neurotrophic factors decreased while compensatory changes emerged, yet persistent excitatory-inhibitory imbalances remained evident. Parallel to these results, NMS rats also showed mechanical and thermal hot hypersensitivity at P24. These findings reveal that despite apparent maternal behavioral compensation following NMS, offspring exhibit neurotrophic-driven developmental dysregulation resulting in persistent spinal circuit alterations. The disconnect between maternal behavioral normalization and sustained molecular changes suggests that early separation stress triggers enduring neurobiological cascades independent of ongoing maternal care quantity, with long-term consequences for sensory processing and pain sensitivity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/736384v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1769b63org.highwire.dtl.DTLVardef@1d396dforg.highwire.dtl.DTLVardef@5647eeorg.highwire.dtl.DTLVardef@8c8db8_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Illouz, H., Poli, A., Brik, Y., Lelievre, V., Poisbeau, P.. 2026-07-09. Maternal behavioral compensation after neonatal separation fails to prevent spinal circuit reprogramming in offspring. https://doi.org/10.64898/2026.07.03.736384

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