Smells connect to memories more than other senses

"The smell of fresh chopped parsley may evoke a grandmother's cooking, or a whiff of a cigar may evoke a grandfather's presence," says author.

man sniffing coffee
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  • The right scent can conjure up a memory more powerfully than most anything else.
  • People who lose their sense of smell often develop symptoms of depression.
  • While other senses connect to the brain's memory center indirectly, the olfactory cortex has a direct line.

    • It's called the Proust effect after a story in the author's "Remembrance of Things Past: Swann's Way." When a character dipped a madeleine, a sweet, buttery French cake, into some lime-blossom tea, the scent suddenly transported him back in time to the moment his aunt had served him that same combination:

      "Immediately the old grey house upon the street, where her room was, rose up like the scenery of a theatre to attach itself to the little pavilion, opening on to the garden, which had been built out behind it for my parents… and with the house the town, from morning to night and in all weathers, the Square where I was sent before luncheon, the streets along which I used to run errands, the country roads we took when it was fine."

      Nothing conjures up a memory so viscerally as the scent with which you associate it. While it's been understood for some time that our olfactory system has a unique ability to vividly summon memories, the mechanism behind the phenomenon has net been well-understood. Now a study by researchers from Northwestern University's Feinberg School of Medicine may have solved the puzzle. The olfactory system has an unusually direct connection to the brain's hippocampus, believed to play an important role in memory.

      The study's published in the journal Progress in Neurobiology.

      A lasting connection

      Credit: schankz/Adobe Stock

      Previous neuroimaging and intracranial electrophysiology investigations have revealed that our senses are functionally connected to the hippocampus, if not directly. However, the new research, for which the principle investigator is Christina Zelano, is the first rigorous comparison of the strength of those connections.

      It turns out that our primary olfactory cortex is a sense that's still directly connected to the hippocampus.

      "This has been an enduring mystery of human experience," Zelano tells Medical Xpress. "Nearly everyone has been transported by a whiff of an odor to another time and place, an experience that sights or sounds rarely evoke. Yet, we haven't known why. The study found the olfactory parts of the brain connect more strongly to the memory parts than other senses. This is a major piece of the puzzle, a striking finding in humans. We believe our results will help future research solve this mystery."

      It's believed that during evolution, the hippocampus' role shifted away from its original strong relationship to the sensory cortexes and toward connections with higher association cortexes. (In rodents, for example, the hippocampus maintains a powerful connection to all sensory cortexes.) It now appears that as this occurred, the olfactory cortex alone continued to be directly wired to the hippocampus.

      "Humans experienced a profound expansion of the neocortex that re-organized access to memory networks," explains Zelano. "Vision, hearing and touch all re-routed in the brain as the neocortex expanded, connecting with the hippocampus through an intermediary-association cortex-rather than directly. Our data suggests olfaction did not undergo this re-routing, and instead retained direct access to the hippocampus."

      The importance of smell

      It's known that people who experience a loss of smell, or "anosmia," often develop depression. "Loss of the sense of smell is underestimated in its impact," says Zelano. "It has profound negative effects of quality of life, and many people underestimate that until they experience it. Smell loss is highly correlated with depression and poor quality of life."

      Anosmia is also associated with COVID-19. "The COVID-19 epidemic," says Zelano, "has brought a renewed focus and urgency to olfactory research." Lead author Guangyu Zhou agrees: "There is an urgent need to better understand the olfactory system in order to better understand the reason for COVID-related smell loss, diagnose the severity of the loss and to develop treatments."

      "Most people who lose their smell to COVID regain it," notes Zelano, "but the time frame varies widely, and some have had what appears to be permanent loss. Understanding smell loss, in turn, requires research into the basic neural operations of this under-studied sensory system."

      She notes that, "While our study doesn't address COVID smell loss directly, it does speak to an important aspect of why olfaction is important to our lives: Smells are a profound part of memory, and odors connect us to especially important memories in our lives, often connected to loved ones."


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      This article was originally published by our sister site, Freethink.

      For the first time, researchers appear to have effectively treated a genetic disorder by directly injecting a CRISPR therapy into patients' bloodstreams — overcoming one of the biggest hurdles to curing diseases with the gene editing technology.

      The therapy appears to be astonishingly effective, editing nearly every cell in the liver to stop a disease-causing mutation.

      The challenge: CRISPR gives us the ability to correct genetic mutations, and given that such mutations are responsible for more than 6,000 human diseases, the tech has the potential to dramatically improve human health.

      One way to use CRISPR to treat diseases is to remove affected cells from a patient, edit out the mutation in the lab, and place the cells back in the body to replicate — that's how one team functionally cured people with the blood disorder sickle cell anemia, editing and then infusing bone marrow cells.

      Bone marrow is a special case, though, and many mutations cause disease in organs that are harder to fix.

      Another option is to insert the CRISPR system itself into the body so that it can make edits directly in the affected organs (that's only been attempted once, in an ongoing study in which people had a CRISPR therapy injected into their eyes to treat a rare vision disorder).

      Injecting a CRISPR therapy right into the bloodstream has been a problem, though, because the therapy has to find the right cells to edit. An inherited mutation will be in the DNA of every cell of your body, but if it only causes disease in the liver, you don't want your therapy being used up in the pancreas or kidneys.

      A new CRISPR therapy: Now, researchers from Intellia Therapeutics and Regeneron Pharmaceuticals have demonstrated for the first time that a CRISPR therapy delivered into the bloodstream can travel to desired tissues to make edits.

      We can overcome one of the biggest challenges with applying CRISPR clinically.

      —JENNIFER DOUDNA

      "This is a major milestone for patients," Jennifer Doudna, co-developer of CRISPR, who wasn't involved in the trial, told NPR.

      "While these are early data, they show us that we can overcome one of the biggest challenges with applying CRISPR clinically so far, which is being able to deliver it systemically and get it to the right place," she continued.

      What they did: During a phase 1 clinical trial, Intellia researchers injected a CRISPR therapy dubbed NTLA-2001 into the bloodstreams of six people with a rare, potentially fatal genetic disorder called transthyretin amyloidosis.

      The livers of people with transthyretin amyloidosis produce a destructive protein, and the CRISPR therapy was designed to target the gene that makes the protein and halt its production. After just one injection of NTLA-2001, the three patients given a higher dose saw their levels of the protein drop by 80% to 96%.

      A better option: The CRISPR therapy produced only mild adverse effects and did lower the protein levels, but we don't know yet if the effect will be permanent. It'll also be a few months before we know if the therapy can alleviate the symptoms of transthyretin amyloidosis.

      This is a wonderful day for the future of gene-editing as a medicine.

      —FYODOR URNOV

      If everything goes as hoped, though, NTLA-2001 could one day offer a better treatment option for transthyretin amyloidosis than a currently approved medication, patisiran, which only reduces toxic protein levels by 81% and must be injected regularly.

      Looking ahead: Even more exciting than NTLA-2001's potential impact on transthyretin amyloidosis, though, is the knowledge that we may be able to use CRISPR injections to treat other genetic disorders that are difficult to target directly, such as heart or brain diseases.

      "This is a wonderful day for the future of gene-editing as a medicine," Fyodor Urnov, a UC Berkeley professor of genetics, who wasn't involved in the trial, told NPR. "We as a species are watching this remarkable new show called: our gene-edited future."

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