Role of brain-derived neurotrophic factor in dysfunction of short-term to long-term memory transformation after surgery and anaesthesia in older mice

Abstract

Background

Memory decline is one of the main manifestations in perioperative neurocognitive disorder. Short-term memory (STM) to long-term memory (LTM) transformation is one aspect of memory consolidation. Early-phase long-term potentiation (E-LTP) to late-phase long-term potentiation (L-LTP) is the molecular correlate of STM to LTM transformation. We examined whether the STM to LTM transformation was impaired after anaesthesia and surgery in older mice.

Methods

Optogenetics and chemogenetics were used to confirm the role of Vglut1+ glutamatergic neurones in the STM to LTM transformation in older mice. Synaptosomes were isolated to analyse expression of brain-derived neurotrophic factor (BDNF). Golgi-Cox staining and hippocampal field potential recordings were also used to measure synaptic plasticity.

Results

We found that the STM to LTM and E-LTP to L-LTP transformations were impaired after anaesthesia and surgery in older mice, and Vglut1+ excitatory neurone activity in the hippocampal CA1 region was reduced. BDNF expression decreased in the postsynaptic fraction, especially in Vglut1+ neurones, whereas cell-type specific overexpression of BDNF in Vglut1+ neurones reversed postoperative STM to LTM transformation dysfunction in older mice.

Conclusions

Reduced BDNF expression was involved in anaesthesia and surgery-induced impairment of the STM to LTM transition involving glutamatergic neurones in the hippocampal CA1 region of older mice. This provides a potential target that might be helpful for understanding and developing treatments for postoperative neurocognitive dysfunction.