Animal studies provide invaluable insights into the senses of sight, hearing, and smell. By examining these senses in animals, researchers have made numerous important discoveries about the underlying mechanisms of sensory perception and what they reveal about human sensory experiences.
Sight
Optical Illusions
Results from experiments on mice at the University of Tokyo have shed new light (literally) on a long-standing neuroscientific question: which levels of neurons within the brain are responsible for the perception of brightness?
The experiment found that a type of visual illusion called neon-color-spreading—in which colors appear to spread into surrounding areas, tricking the eye into thinking color exists where it does not—works on mice as well as humans.
The results suggest that mice can be effective stand-ins for experiments when humans cannot be used, such as those that record neural activity.
Treating Retinal Disease
A research team from Harvard University and the Broad Institute has been able to partially restore vision in blind mice. The team used prime editing, a gene editing approach that has been proposed as a more accurate and safer alternative to CRISPR, to treat two different mouse models with genetic retinal disease.
To transport the prime editors to the eyes of the mice, the researchers used a delivery system called prime editor engineered virus-like particles, or PE-eVLPs, which they claim is the first time protein-RNA complexes have been used to achieve therapeutic prime editing in an animal.
In mouse models of retinal disease similar to retinitis pigmentosa, the treatment successfully corrected the gene mutation. In a mouse model with more severe retinal disease, the prime editors were able to correct the mutation more effectively than other methods that have been used in the past, resulting in substantial improvements in the visual function of the mice.
The team plans to adapt the method to work on other tissue types.
Regenerating Optic Nerves
Researchers at Boston Children’s Hospital have been able to regenerate optic nerve fibers in mice by using growth-promoting genes and blocking natural growth inhibitors. After treatment, previously blind mice turned their heads to follow patterns of moving bars.
Previous efforts have deleted or blocked tumor suppressor genes to enable optic nerve fiber regeneration, but that can also promote cancer growth. The new approach does not interfere with tumor suppressor genes.
The new treatment uses three growth factors—osteopontin, insulin-like growth factor 1, ciliary neurotrophic factor—and a potassium channel blocker, 4-aminopyridine (4-AP), which is marketed as AMPYRA for multiple sclerosis.
The team is now testing whether injecting a combination of growth factor proteins directly into the eye could be equally effective.
Blindness-Causing Gut Bacteria
A team of researchers at the UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust has discovered a connection between gut bacteria and certain types of blindness.
The international study found that eyesight loss caused by a specific genetic mutation—of the Crumbs homolog 1 (CBR1) gene, which is associated with Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP)—may be caused by gut bacteria, and can potentially be treated with antimicrobials.
In a study with mouse models, the team found that gut bacteria was present in damaged areas of the eye. They determined that the mutation may cause the body to lower its defenses, allowing the bacteria to enter the eye and cause lesions in the retina that eventually lead to blindness.
Smell
Rat Cells Restore Sense of Smell in Mice
Researchers at Columbia University have used neural stem cells from rats to restore olfactory neural circuits in mice.
The team developed chimeric mice with rat neurons, using a procedure called interspecies blastocyst complementation (IBC) to inject cells from one species into embryos of another and then implant the embryos into animals of their own species.
After implantation, the rat cells not only integrated into the mouse brains, they also restored the sense of smell in mice that lacked the sensory neurons for smell.
In addition to restoring the sense of smell, the team hopes the chimeric mice can facilitate the study of neurological diseases and enable the development of more human-like brain tissues.
Smell, Aging, and Reproduction
Researchers from New Zealand and Australia have uncovered an interesting connection between sense of smell, aging, and reproduction.
The team found that exposing middle-aged to old male mice to the scent of an unknown female reduced the number of litters the males could sire. It also reduced the lifespan of the male mice if they were allowed to mate.
The findings indicate that sensory perception of mates may be an important driver of physiological change in mammals.
How Smell Influences Decision-Making
Researchers at the University of Colorado have discovered that odors stimulate specific brain cells that may play a role in how the brain makes decisions.
The team examined “time cells” in the hippocampus of mice, an area known to be key to memory and learning. Mice were given a choice of two different smells—a fruity smell and the smell of mineral oil. If they chose the fruity smell, they were rewarded with sweet water from a spout. They quickly learned to lick the spout when they smelled the fruity smell as opposed to the mineral oil smell.
The finding is significant because it was previously not known that there were decision-making cells in the hippocampus. The new study shows that smells serve as more than just reminders of past experiences—they can also help guide decision-making.
Menthol and Alzheimer’s
Menthol can clear your sinuses and has been shown to boost immune functioning in mice, but according to a new mouse study, it might also be able to improve brain functioning.
A team of researchers in Spain found that mouse models of Alzheimer’s show improved cognitive abilities after inhaling menthol. The chemical compound in menthol appears to stop damage to the brain caused by Alzheimer’s, at least to some degree.
Brief exposures to menthol for six months prevented cognitive decline in Alzheimer’s mice and improved the cognitive ability of healthy young mice.
While more research is needed before the discovery can be translated into any type of treatment for humans, the study is an important step toward understanding the connection between smell and the brain.
Hearing
Restoring Hearing in Mice
A study out of Kings College London has successfully reversed hearing loss in mice.
The team focused on deafness caused by a defective Spns2 gene. In mice bred to have a defective Spns2 gene, the researchers gave the mice an enzyme to activate the gene, restoring their hearing abilities in the low and middle frequency ranges.
Researchers at the University of Southern California have also been investigating ways to address hearing loss, and may have found a way to restore hearing.
The sensory hearing cells of the inner ear don’t regenerate after damage, which makes hearing impossible to recover. However, non-sensory supporting cells in the inner ear can be converted to sensory cells if a process called “epigenetic silencing,” which shuts off the genes required for this conversion, is reversed.
Tamiflu for Hearing Loss
Tamiflu (oseltamivir phosphate) is an antiviral medicine used to treat influenza, but a recent study has identified another potential use for the drug: reversing noise-related hearing loss.
Unlike congenital deafness, noise-related hearing loss is caused by cell death due to prolonged exposure to loud noise. Researchers at Creighton University and St. Jude Children’s Research Hospital administered oseltamivir phosphate orally to two different mouse models and found that it protected against cisplatin and noise-induced hearing loss in both male and female mice.
Gene Therapy Restores Hearing in Human
In a groundbreaking trial, 18-month-old Opal Sandy, who suffered from auditory neuropathy, regained her hearing through gene therapy. The treatment, part of the CHORD trial, was based on successful studies in mice that used gene replacement therapy to restore hearing.
Opal responded to sound within four weeks after the treatment and attained near-normal hearing levels within 24 weeks. With 10 out of 11 children already benefiting from the therapy in the trial, the approach offers hope for the future of genetic disease treatment.
