Mouse models of Rett Syndrome have rerecalled memory after cell activation

Mouse models of Rett Syndrome have rerecalled memory after cell activation ...

Researchers in the laboratory of Dr. Huda Zoghbi, a distinguished service professor at Baylor College of Medicine and director of the Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital, have discovered that the decreased memory recall of Rett syndrome mice can be restored by activating specific inhibitory cells in the hippocampus. These findings are published in the current edition ofNeuron.

Rett syndrome is a neurodevelopmental disorder characterized by loss of acquired cognitive, motor, language, and social abilities after the first year of life, as well as profound learning and memory impairments. In particular, contextual memories, those that encode an event and the circumstances in which the event was experienced, are diminished in mouse models. Previous research has suggested that decreased contextual memories are related to disruptions in the finely tuned balance between excitatory and inhibitory synaptic inputs that constantly bombard hippocampal neurons.

Using a miniature microscope, the Zoghbis team imagined that disruptions in this balance may alter the size and composition of ensembles of hippocampal neurons necessary to encode a contextual memory. Interestingly, these groups of mice were monitored independently in response to a worried experience, indicating that hippocampal pyramidal neurons are not receiving enough inhibition. According to Lingjie He, a postdoctoral associate in the Zoghbi lab and the first author, an optimal balance between excitatory

The next major question that the team asked was whether or not the neuron is proponenting the inhibition?

The researchers used brain slices to find neuronal activity from identified cell types. They found a significant reduction in connectivity between pyramidal cells and a subset of somatostatin-expressing (SOM) inhibitory neurons. They found that these cells, which were normally recruited by hippocampal pyramidal neurons during memory recall, were poor engaged in Rett mice.

This led the team to wonder if activating these inhibitory neurons during memory recall would aid Rett mice remember better. Using a chemical-genetic technique that allows for the activation of a specific cell type, somatostatin expressing cells in Rett mice enhanced contextual memory recall.

According to Zoghbi, the first study to demonstrate that upregulating the activity of SOM neurons can improve memory recall and retrieval capacity in Rett mice. It opens broad opportunities of research to explore therapeutic possibilities that may improve contextual memory recall in individuals affected by Rett syndrome. These findings have a much wider meaning and are also applicable to other neurological disorders in which the development and function of inhibitory circuits are altered.

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