Biology subjects

Grade, S.

Publications and source records attributed to Grade, S..

3 recordsLinked to original sources

bioRxiv2026

Adaptive brain rewiring after brain injury via adult neurogenesis

The adult mammalian brain has limited regenerative capacity yet retains substantial potential for functional reorganization after experience, injury or disease1-3. While local plasticity at injury sites has been described4,5, the brain-wide consequences of a focal injury and the biological processes that drive them remain unknown. To address this, we performed an unbiased, whole brain screen of neuronal activity at single cell resolution following a focal injury to the primary visual cortex (V1) in mice. Olfactory processing areas emerged as loci of remote activation. We further show that V1 injury promotes the recruitment of adult born neurons into the olfactory bulb (OB) and potentiates cortical feedback onto bulbar circuits. Combining high-density multielectrode array recordings with two-photon calcium imaging revealed OB circuit refinement characterized by increased synchrony and sharpened tuning of principal output neurons. These circuit-level functional enhancements coincide with improved behavioral performance in odor-guided tasks. Motor cortex lesions do not elicit similar cellular and behavioral responses, suggesting that such distal adaptation only develops when injury is coupled with increased olfactory demand. Together, these data demonstrate that the adult brain can recruit alternative sensory circuits distant from a focal lesion to undergo adaptive, functionally relevant reorganization, and implicate adult neurogenesis as a contributing mechanism. Our findings expose a previously underappreciated degree of remote plasticity and reveal a novel role of adult neurogenesis in sensory compensation.

neuroscience↗

bioRxiv2026

Improved myelin clearance and cognitive outcomes after TBI in female mice are mediated by ovarian steroids and sex chromosomes

Traumatic brain injury (TBI) causes sex-specific memory deficits, yet the underlying mechanisms are not fully understood. Using a mouse TBI model, we investigated the role of reactive astrocytes in sex-specific outcome. TBI provoked long-term contextual memory impairment in males and ovariectomized females, but not in intact females. The synthetic steroid tibolone preserved memory and cFos+ neuronal density in the hippocampus of ovariectomized females. Hormone deprivation upregulated astrocytic GFAP and S100B, reduced Homer1, and impaired myelin phagocytosis by astrocytes in females. These effects were counteracted by tibolone. In Four-Core-Genotype mice, memory loss correlated with reduced astrocytic myelin uptake and neuronal activity in XX males and XY female animals. Astrocyte transplantation showed that female astrocytes exhibit superior myelin clearance capacity, especially in female brain environments, though they outperform male astrocytes in both sex contexts. These findings identify astrocyte-mediated myelin phagocytosis as a key mechanism for memory preservation after TBI, governed by both hormonal and chromosomal sex factors.

neuroscience↗

bioRxiv2021

Brain injury environment critically influences the connectivity of transplanted neurons

Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative connectomics unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain, versus exuberant after trauma. In the latter, excessive synapse pruning follows the initial overshoot of connectivity resulting in only a few connections left. Proteomic profiling identifies candidate molecules involved in the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits. TeaserNeuronal grafts in a brain area affected by trauma receive excessive yet mostly vulnerable inputs from host circuits.

neuroscience↗