Combined loss of brevican, neurocan, tenascin-C and tenascin-R leads to impaired fear retrieval due to perineuronal net loss

This study investigates the role of specific molecules in the brain's extracellular matrix (ECM) in fear memory processes. It uses mice lacking four key ECM molecules: brevican, neurocan, tenascin-C, and tenascin-R, referred to as 4x KO mice. The research focuses on how these molecules, which form structures called perineuronal nets (PNNs), affect the ability of mice to remember learned fear. The study looks at the amygdala-medial prefrontal cortex (mPFC) circuit, which is important for creating and maintaining fear memories. The study found that mice lacking these ECM molecules had difficulty retrieving previously learned fear memories and had reduced PNN density in brain regions associated with fear memory.

• 1
  Mice lacking brevican, neurocan, tenascin-C, and tenascin-R (4x KO) exhibited impaired fear memory consolidation, indicated by their inability to retrieve previously learned fear memories.
• 2
  The 4x KO mice showed reduced perineuronal net (PNN) density and disturbed synaptic integrity in brain regions crucial for fear memory, such as the amygdala and medial prefrontal cortex (mPFC).
• 3
  Neural activity, specifically cFOS expression intensity, was reduced in the basolateral amygdala (BL) and prelimbic cortex (PrL) of 4x KO mice during fear retrieval, suggesting altered neuronal network activity.