The sharp-wave ripple (SWR) is a neuronal activity spontaneously occur in the hippocampus. During each SWR, neuronal assemblies coding animals? experiences are reactivated in a temporally compressed manner. This compressed replay is critical for the consolidation of episodic memory. SWRs occur thousands of times every hour, during sleep and quiet restfulness. The occurrence rate reduces with aging and after hippocampal damage resulting from Alzheimer?s disease (AD) and other neurodegenerative conditions. Reduced SWR occurrence rate and quality may contribute to the impairment of memory consolidation of recent experiences. We propose to use ?pacing? (micro-electric shocks at a given rate) to prime the occurrence of SWRs, and to examine whether pacing SWR can improve spatial memory of Alzheimer animal models.
Two Specific Aims are proposed:
Aim 1 To achieve minimally invasive pacing in free-moving animals through wireless stimulation via an electrode placed in the lateral ventricles, outside of the hippocampus tissue. Preliminary results have demonstrated that SWRs can be induced by non-contact stimulation, by weak electrical field affecting the CA3 tissue in hippocampal slices. Experiments under Aim 1 will extend the preliminary results from brain slice to whole animals, establishing an electrical-field stimulation in lateral ventricle.
Aim 2 To test if ?artificial SWRs? induced by pacing can contribute to memory consolidation. We will also test if pacing can improve memory consolidation in AD model (Tg2567) animals. These animals develop significant deficits in spatial memory at 6-8 months of age. We will test if pacing can improve spatial memory in behavioral tests. Deterioration of hippocampus-dependent episodic memory is a hallmark of Alzheimer dementia and other brain degeneration conditions. The proposal will be a first step in develop a therapeutic strategy for improving memory with a non-pharmaceutical method, and less invasive than deep brain stimulation.
This project investigates whether memory can be improved in Alzheimer animal models when the abundance of hippocampus sharp-wave-ripple (SWR) is increased by micro-electric shocks. SWR is a neuronal activity that is critical for memory consolidation. The research will contribute to enhancing the memory for individuals battling neurodegenerative diseases.
