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Frontiers in Neuroscience 2023Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was... (Review)
Review
OBJECTIVE
Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults.
METHODS
Male and female older adults ( = 43), age 60-85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months.
RESULTS
A statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity.
CONCLUSION
Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.
PubMed: 37554295
DOI: 10.3389/fnins.2023.1200448 -
Nature Sep 2023Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing. Suckling triggers the release...
Oxytocin is a neuropeptide that is important for maternal physiology and childcare, including parturition and milk ejection during nursing. Suckling triggers the release of oxytocin, but other sensory cues-specifically, infant cries-can increase the levels of oxytocin in new human mothers, which indicates that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit that routes auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice that were presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not to pure tones, through input from the posterior intralaminar thalamus, and that repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behaviour in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for efficient parenting.
Topics: Animals; Female; Mice; Cues; Hypothalamus; Maternal Behavior; Neural Pathways; Neurons; Oxytocin; Photometry; Thalamic Nuclei; Vocalization, Animal; Wakefulness
PubMed: 37730989
DOI: 10.1038/s41586-023-06540-4 -
Neuron Oct 2023The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it...
The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATm) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATm population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATm neurons or multiple downstream pathways. In awake mice, ATm activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.
Topics: Mice; Animals; Arousal; Thalamus; Wakefulness; Neurons; Synaptic Transmission
PubMed: 37557180
DOI: 10.1016/j.neuron.2023.07.007 -
Aging Cell Sep 2023Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this...
Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
Topics: Humans; Animals; Mice; NAD; Peroxisome Proliferator-Activated Receptors; Presbycusis; Cochlea; Dietary Supplements
PubMed: 37395319
DOI: 10.1111/acel.13909 -
Neuron Nov 2023Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their...
Safety assessment and threat evaluation are crucial for animals to live and survive in the wilderness. However, neural circuits underlying safety assessment and their transformation to mediate flexibility of fear-induced defensive behaviors remain largely unknown. Here, we report that distinct neuronal populations in mouse anterior cingulate cortex (ACC) encode safety status by selectively responding under different contexts of auditory threats, with one preferably activated when an animal staysing in a self-deemed safe zone and another specifically activated in more dangerous environmental settings that led to escape behavior. The safety-responding neurons preferentially target the zona incerta (ZI), which suppresses the superior colliculus (SC) via its GABAergic projection, while the danger-responding neurons preferentially target and excite SC. These distinct corticofugal pathways antagonistically modulate SC responses to threat, resulting in context-dependent expression of fear reactions. Thus, ACC serves as a critical node to encode safety/danger assessment and mediate behavioral flexibility through differential top-down circuits.
Topics: Mice; Animals; Gyrus Cinguli; Fear; Superior Colliculi; Zona Incerta
PubMed: 37652003
DOI: 10.1016/j.neuron.2023.08.008