When Alzheimer’s degrades cells that cross hemispheres, visual memory suffers

A new MIT study finds that Alzheimer’s disease disrupts at least one form of visual memory by degrading a newly identified circuit that connects the vision processing centers of each brain hemisphere.

The results of the study, published in Neuron by a research team based at The Picower Institute for Learning and Memory, come from experiments in mice, but provide a physiological and mechanistic basis for prior observations in human patients: the degree of diminished brain rhythm synchrony between counterpart regions in each hemisphere correlates with the clinical severity of dementia.

“We demonstrate that there is a functional circuit that can explain this phenomenon,” said lead author Chinnakkaruppan Adaikkan, a former Picower Institute postdoc who is now an assistant professor in the Centre for Brain Research at the Indian Institute of Science (IISc) in Bangalore. “In a way we uncovered a fundamental biology that was not known before.”

Specifically, Adaikkan’s work identified neurons that connect the primary visual cortex (V1) of each hemisphere and showed that when the cells are disrupted, either by genetic alterations that model Alzheimer’s disease or by direct laboratory perturbations, brain rhythm synchrony becomes reduced and mice become significantly less able to notice when a new pattern appeared on a wall in their enclosures. Such recognition of novelty, which requires visual memory of what was there the prior day, is an ability commonly disrupted in Alzheimer’s.

“This study demonstrates the propagation of gamma rhythm synchrony across the brain hemispheres via the cross hemispheric connectivity,” said study senior author Li-Huei Tsai, Picower Professor and director of The Picower Institute and MIT’s Aging Brain Initiative. “It also demonstrates that the disruption of this circuit in AD mouse models is associated with specific behavioral deficits.”

Cross-hemispheric cells

In the study, Adaikkan, Tsai, Thomas McHugh and co-authors discovered and traced V1 neurons that extended their axons all the way through the corpus callosum, which connects the brain’s hemispheres, to cells in the V1 on the brain’s other side. There, they found, the cross-hemispheric (CH) neurons forged connections, or synapses, with target cells, providing them with “excitatory” stimulation to drive their activity. Adaikkan also found that CH neurons were much more likely to be activated by a novelty discrimination task than V1 neurons in general or neurons in other regions heavily involved in memory such as the hippocampus or the prefrontal cortex.

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