Synaptic degeneration in neuronal circuits hinders memory recall, memory rescue, and learning

Neurodegeneration is a characteristic of Alzheimer’s disease (AD), but its effect on neural activity dynamics underlying memory deficits is unclear. Here, we studied the effects of synaptic degeneration on neural activities associated with memory recall, memory rescue by slow-gamma stimulation, and learning a new memory, in an integrate-and-fire neuronal network. Our results showed that reducing connectivity decreases the neuronal synchronisation of memory neurons at slow-gamma frequencies and impairs memory recall performance. Although slow-gamma stimulation rescued memory recall and slow-gamma oscillations, the rescue with reduced connectivity caused a side effect of activating mixed memories. During the learning of a new memory, reducing connectivity caused an impairment in storing the new memory, but did not affect previously stored memories. Our results reveal potential computational mechanisms underlying the memory deficits caused by synaptic degeneration in AD.