Researchers at The Picower Institute for Learning and Memory at MIT report that Alzheimer’s disease disrupts at least one form of visual memory in mice by degrading a newly identified circuit that connects the vision processing centers of each brain hemisphere. The team’s study “Alterations in a cross-hemispheric circuit associates with novelty discrimination deficits in mouse models of neurodegeneration” appears in Neuron.
Although the results come from experiments in mice, the scientists explain that the research provides 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.
“A major pathological hallmark of neurodegenerative diseases, including Alzheimer’s, is a significant reduction in the white matter connecting the two cerebral hemispheres, as well as in the correlated activity between anatomically corresponding bilateral brain areas. However, the underlying circuit mechanisms and the cognitive relevance of cross-hemispheric (CH) communication remain poorly understood,” write the investigators.
“These data reveal a hitherto uncharacterized CH circuit in the visual cortex, establishing a causal link between this circuit and novelty discrimination behavior and highlighting its impairment in mouse models of neurodegeneration.”
“We demonstrate that there is a functional circuit that can explain this phenomenon,” said lead author Chinnakkaruppan Adaikkan, PhD, 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, the scientists’ 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, PhD, 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.”
All together, the study results show that CH cells in V1 connect with neurons in the counterpart area of the opposite hemisphere to synchronize neural activity needed for properly recognizing novelty, but that Alzheimer’s disease damages their ability to do that job.
Adaikkan said he is curious to now look at other potential cross-hemispheric connections and how they may be affected in Alzheimer’s disease, too. He said he also wants to study what happens to synchrony at other rhythm frequencies.
