Biology subjects

Castello-Waldow, T.

Publications and source records attributed to Castello-Waldow, T..

2 recordsLinked to original sources

bioRxiv2025

Direct Evidence for Dendritic Spine Compensation and Regeneration in Alzheimer Disease Models

Dendritic spine loss in Alzheimers disease (AD) strongly correlates with cognitive decline, whereas spine preservation is associated to cognitive resilience. Yet, whether and how neurons compensate for spine loss in AD remains largely unknown. Using a chromophore-assisted light inactivation approach (CALI), we developed a tool to selectively eliminate dendritic spines to model this key feature of AD. Using in vivo and in vitro two-photon imaging, we discovered that the artificial elimination of spines triggers a two-stage compensatory response: rapid enlargement of remaining spines followed by delayed spine regeneration. Remarkably, similar structural plasticity was observed across multiple {beta}-amyloid-driven models of synapse loss, including the APP/PS1 mouse and following intracortical delivery of oligomeric {beta}-amyloid. Mechanistically, compensatory spine enlargement required NMDA receptor activation and de novo protein synthesis. These findings suggest that neurons retain an intrinsic capacity to reverse early synaptic loss in AD, potentially contributing to cognitive resilience.

neuroscience↗

bioRxiv2020

Aberrant structural synaptic dynamics precede disorganization of temporal and spatial coding in the hippocampus upon repeated stress exposure

Stress exposure strongly contributes to the pathophysiology of psychiatric diseases such as depression, schizophrenia, anxiety, and post-traumatic stress disorder. It also affects both function and structure of hippocampal CA1, leading to episodic memory impairment. Here, we used deep-brain optical imaging to elucidate the effects of stress on CA1 pyramidal neuron structural connectivity and activity. We tracked dynamics of dendritic spines during repeated stress and found decrease in spinogenesis followed by decrease in spine stability. In contrast to repeated stress, acute stress led to stabilization of the spines born in temporal proximity to the stressful event. To investigate the link between structural plasticity and activity patterns upon repeated stress, we studied the activity of thousands of CA1 pyramidal neurons in freely-moving. We found an increase in activity and loss of temporal organization followed by a disruption in temporal and spatial coding. Our data suggest that stress-induced sustained increase in activity leads to loss of structural connectivity and subsequent temporal and spatial coding impairments.

neuroscience↗