Memory retrieval by targeted brain stimulation may provide a means to treat the early stages of Alzheimer's disease (AD) and other neurological diseases where patients show memory loss.
Currently, episodic memory deficits in pathological conditions, for example AD, are treated by medications, such as cholinesterase inhibitors or memantine, that lessen or stabilize cognitive function for a limited duration of time. These medications stall memory decay by supporting interneuronal communication. However, no treatment currently exists to treat the disease-induced changes in the structure and function of neurons themselves. Novel therapeutic strategies are needed to treat the root cause of memory loss by restoring neuronal structure and function.
This invention comprises a method to identify and rescue the structure and function of special engram neurons of the dentate gyrus of the hippocampus, which are involved in the storage and retrieval of episodic memories, and which show reduced dendritic growth in AD. These engram neurons, and the axons projecting toward them, can be identified through special optogenetic technology that selectively labels cells activated during learning. Once the cells of interest are identified, a series of targeted high-frequency optical stimulations can induce the growth of dendritic structures that are normally absent in diseased brains. The coupling of learning-dependent optogenetic labeling to targeted stimulation in mouse models of AD has been shown to lead to the retrieval of long term memories from several different learning tasks. This method looks to be a promising strategy in many neurological conditions where dendritic abnormalities in select neuron populations may be the cause of memory loss. Furthermore, it may be applied broadly to any condition where low dendritic growth in a specific population of active neurons leads to their abnormal function.
Treats the root cause of memory loss in the early stages of AD
Identifies and restores neuronal structure and function
Broad applicability to any pathological condition involving low dendritic growth in active neurons