Work

LIMK1 Deficiency Disrupts Hippocampal–Cortical Memory Consolidation and Attenuates Trauma-Induced PTSD-like Behavior

Year: 2025

Type: article

Abstract: Memory consolidation is the process by which newly acquired experiences are stabilized into long-term memory, involving coordinated cellular and network-level activity across brain regions such as the hippocampus and prefrontal cortex. Dysregulation of this process has been implicated in psychiatric disorders including post-traumatic stress disorder (PTSD), which is characterized by the over-consolidation of traumatic memories. LIM kinase 1 (LIMK1), a key regulator of synaptic plasticity, is believed to play an important role in memory consolidation across hippocampal–cortical circuits. In this study, we investigated the function of LIMK1 using Limk1 knockout mice. Behavioral tests such as the novel object location memory task revealed significant memory impairments in knockout animals. In vivo recordings during sleep showed disrupted communication between the hippocampus and prefrontal cortex, suggesting impaired systems-level consolidation. Furthermore, in an underwater trauma exposure model, pharmacological inhibition of LIMK1 with LIMK-i3 alleviated trauma-induced behavioral abnormalities. These findings highlight LIMK1 as a critical mediator of hippocampal–cortical memory consolidation and provide experimental evidence that LIMK1 inhibition can modulate maladaptive memory processes associated with PTSD-like symptoms.

Source: Biology

DOI: 10.3390/biology14111560