91³Ō¹Ļ

91³Ō¹Ļ researchers uncover new connection between smell and memory

Findings offer opportunities for improved smell tests in Alzheimerā€™s disease diagnosis
Photo of mouse sniffing cotton swab
A mouse is guided by its memory to search for an odour that was once present on the cotton swab (photo courtesy of Afif Aqrabawi)

Neurobiologists at the 91³Ō¹Ļ have identified a mechanism that allows the brain to recreate vivid sensory experiences from memory, shedding light on how sensory-rich memories are created and stored in our brains.

Using smell as a model, the findings offer a novel perspective on how the senses are represented in memory, and could explain why the loss of the ability to smell has become recognized as an early symptom of Alzheimerā€™s disease.

ā€œOur findings demonstrate for the first time how smells weā€™ve encountered in our lives are recreated in memory,ā€ said Afif Aqrabawi, a PhD candidate in the department of cell and systems biology in the Faculty of Arts & Science at 91³Ō¹Ļ, and lead author of .

ā€œIn other words, weā€™ve discovered how you are able to remember the smell of your grandmaā€™s apple pie when walking into her kitchen.ā€

There is a strong connection between memory and olfaction ā€“ the process of smelling and recognizing odours ā€“ owing to their common evolutionary history. Examining this connection in mice, Aqrabawi and graduate supervisor Junchul Kim, an assistant professor in the department of psychology at 91³Ō¹Ļ, found that information about space and time integrate within a region of the brain important for the sense of smell ā€“ yet poorly understood ā€“ known as the anterior olfactory nucleus (AON).

ā€œWhen these elements combine, a what-when-where memory is formed,ā€ said Aqrabawi. This is why, for example, you might have the ability to remember the smell of a loverā€™s perfume (the what) when you reminisce about your first kiss (the when and where).

Curious about the function of the anterior olfactory nucleus, Aqrabawi and Kim designed a series of tests to exploit the preference of mice to sniff new odours.

ā€œThey prefer to spend more time smelling a new odour than one thatā€™s familiar to them,ā€ said Aqrabawi. ā€œWhen they lose this preference, itā€™s implied they no longer remember the smell even though they have sniffed it before, so they continue to smell something as if for the first time.ā€

In the course of examining the structure and function of the AON, the researchers uncovered a previously unknown neural pathway between it and the hippocampus ā€“ a structure critical for memory and contextual representation, and highly implicated in Alzheimerā€™s disease. They found they could mimic the odour memory problems seen in Alzheimerā€™s patients by disconnecting communication between the hippocampus and the AON.

Whereas the mice whose hippocampus-AON connection was left intact refrained from returning to familiar locations to sniff odours that were no longer novel, those with a disconnected pathway returned to sniff previously smelled odours for longer periods of time. Replicating early degeneration of the AON demonstrated the inability of the when-where context to complete the function and provide the what of the odour memory.

ā€œIt demonstrates that we now understand which circuits in the brain govern the episodic memory for smell. The circuit can now be used as a model to study fundamental aspects of human episodic memory and the odour memory deficits seen in neurodegenerative conditions,ā€ said Aqrabawi.

There is a vast body of work that reports olfactory dysfunction ā€“ particularly olfactory memory loss ā€“ as symptoms of the onset of Alzheimerā€™s disease. Such deficits in the ability to recognize odours precede the cognitive decline and are correlated with the degree of illness.

The AON has a well-documented involvement in Alzheimerā€™s disease but not much else is known about its function. It has consistently been reported to be among the earliest sites of neurodegeneration including the formation of neurofibrillary tangles, which are abnormal proteins found in Alzheimerā€™s patients.

Because of this, smell tests are now used in the hopes of detecting the early onset of Alzheimerā€™s, yet they are imperfectly designed since the underlying cause of the olfactory problems remains unknown.

ā€œGiven the early degeneration of the AON in Alzheimerā€™s disease, our study suggests that the odour deficits experienced by patients involve difficulties remembering the ā€˜whenā€™ and ā€˜whereā€™ odours were encountered,ā€ said Kim.

The researchers say that with a better understanding of the neural circuits underlying odour memory, tests that directly and effectively examine the proper functioning of these circuits can be developed.

ā€œSuch tests might be more sensitive to detecting problems than if patients were prompted to remember an odour itself,ā€ said Kim. ā€œThe motivation to develop them is high due to their quick, cheap, and easy administration.ā€

The findings are described in the study ā€œHippocampal projections to the anterior olfactory nucleus differentially convey spatiotemporal information during episodic odour memory,ā€ published this month in Nature Communications. Support for the research was provided by the Canadian Institutes for Health Research and the Natural Sciences and Engineering Research Council of Canada.

 

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