Visual memory hampered when Alzheimer’s disease degrades cells that cross the brain hemispheres

Researchers at MIT’s Picower Institute for Learning and Memory 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 cerebral hemisphere. The team’s study “Alterations in a crossed hemispheric circuit associated 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 previous observations in human patients: the degree of synchronization of decreased brain rhythm between homologous regions of each hemisphere is in correlation with clinical severity of dementia.

“A major pathological hallmark of neurodegenerative diseases, including Alzheimer’s disease, is a significant reduction in white matter connecting the two cerebral hemispheres, as well as correlated activity between anatomically corresponding bilateral brain areas. However, the underlying circuit mechanisms and cognitive relevance of inter-hemispheric (CH) communication remain poorly understood,” the researchers write.

A research team traced neurons projecting from the anterior cingulate cortex (right, red) to the motor cortex (left, green). Note that the images are at different scales. [Daigo Takeuchi/Picower Institute]

“Here, we show that novelty discrimination behavior activates CH neurons and enhances homotopy synchronized neural oscillations in the visual cortex. CH neurons provide the excitatory drive required for synchronous neuronal oscillations between hemispheres, and unilateral inhibition of the CH circuit is sufficient to impair synchronous oscillations and novelty discrimination behavior. In 5XFAD and Tau P301S mouse models, CH communication is impaired and novelty discrimination is impaired.

“These data reveal a previously 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 postdoctoral fellow who is now an assistant professor at the Center for Brain Research at Indian Institute of Science (IISc) in Bangalore. “In a way, we discovered 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 cells are disrupted, either by genetic alterations modeling Alzheimer’s disease or by direct disruptions in the lab, brain rhythm synchronization is reduced, and mice become much less able to notice when a new pattern appears on a wall in their enclosure. Such recognition of novelty, which requires a visual memory of what was there the day before, is a commonly impaired ability in Alzheimer’s disease.

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

Overall, the study results show that V1 CH cells connect to neurons in the homologous area of ​​the opposite hemisphere to synchronize neural activity necessary for the correct recognition of novelty, but that the disease Alzheimer’s damages their ability to do this job.

Adaikkan said he was curious to now examine other potential connections between the hemispheres and how they might also be affected in Alzheimer’s disease. He said he also wanted to study what happens to synchrony at other rhythmic frequencies.

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