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Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body β and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.

Neonicotinoid insecticides, the fastest-growing class in recent decades, interfere with cholinergic neurotransmission by binding to the nicotinic acetylcholine receptor. This disruption affects both targeted and non-targeted insects, impairing cognitive functions such as olfaction and related behaviors, with a particular emphasis on olfactory memory due to its ecological impact. Despite the persistent presence of these chemicals in the environment, significant research gaps remain in understanding the intricate interplay between cognitive function, development, neuronal activity, and neonicotinoid-induced toxicity. This study focuses on the fruit fly Drosophila melanogaster, chosen for its genetic tractability, well-characterized neural circuitry, and remarkable parallels with bees in neurotransmitter systems and brain structures. Our aim is to establish the fruit fly as a valuable model organism for studying the effects of neonicotinoids on behavior and neuronal circuitry, with particular attention to olfactory memory and associated brain circuitries. To achieve this aim, we conducted experiments to investigate the effects of short-term exposure to sublethal doses of the neonicotinoid imidacloprid, mimicking realistic environmental insecticide exposure, on the formation of odor memories. Additionally, we evaluated synaptic contacts and cholinergic neurotransmission within the mushroom body, the primary memory network of insects. Our results showed significant impairments in odor memory formation in flies exposed to imidacloprid, with exposure during the adult stage showing more pronounced effects than exposure during the larval stage. Additionally, functional studies revealed a decrease in synaptic contacts within the intrinsic olfactory projection neurons and the mushroom body. Furthermore, another experiment showed an odor-dependent reduction in cholinergic neurotransmission within this network. In summary, employing Drosophila as a model organism provides a robust framework for investigating neonicotinoid effects and understanding their diverse impacts on insect physiology and behavior. Our study initiates the establishment of the fruit fly as a pivotal model for exploring neonicotinoid influences, shedding light on their effects on olfactory memory, neuronal integrity, and synaptic transmission.

Recent studies highlight how body psychotherapy is becoming highly cited, especially in connection with studies on trauma-related disorders. This review highlights the theoretical assumptions and recent points in common with embodied simulation and new sensory theories by integrating bioenergetic analysis, embodiment, and olfactory memory in trauma and post-traumatic stress disorder (PTSD) therapy. Embodied memory, rooted in sensorimotor experiences, shapes cognitive functions and emotional responses. Trauma, embodied in somatic experiences, disrupts these processes, leading to symptoms such as chronic pain and dissociation. The literature discussed highlights the impact of burning odors on individuals with PTSD and those who have experienced childhood maltreatment. Burning odors can increase stress and heart rate in war veterans, with sensitivity to these odors intensifying over time since the trauma. Additionally, adults who experienced childhood maltreatment exhibit faster processing of unpleasant odors and increased symptom severity. Grounding techniques, such as adopting a balanced posture, enhance breathing and sensory capabilities, potentially aiding in managing symptoms associated with trauma-related disorders such as PTSD.

IntroductionOlfaction is impaired in Alzheimer’s disease (AD). However, olfactory memory has rarely been examined. As the pathogenesis of AD remains largely unknown, collecting more data regarding the occurrence and progression of its symptoms would help gain more insight into the disease.ObjectiveTo investigate olfactory memory and its relationship with verbal memory and other clinical features in patients with early-stage AD.MethodsThree groups of participants were enrolled in this study: patients with mild dementia due to AD (MD-AD, N = 30), patients with mild cognitive impairment due to AD (MCI-AD, N = 30), and cognitively normal older participants (CN, N = 30). All participants underwent cognitive evaluation (Clinical Dementia Rating scale, Mini Mental State Examination, Alzheimer’s Disease Assessment Scale–Cognitive Subscale, delayed verbal recall, and verbal fluency tests) and assessment of olfactory immediate and delayed recognition memory.ResultsOlfactory immediate and delayed recognition memory scores were significantly lower in the MD-AD group than in the MCI-AD and CN groups. The MCI-AD and CN groups did not differ significantly [in both cases, Kruskal–Wallis test, p 0.05)]. Verbal immediate recall, delayed recall after 5 min, and delayed recall after 30 min scores were significantly worse in the MD-AD and MCI-AD groups than in the CN group. MD-AD and MCI-AD groups did not differ significantly [in all cases Kruskal–Wallis test, p 0.05)]. Duration of AD symptoms was a strong predictor of both immediate and delayed olfactory recognition memory scores.ConclusionOlfactory memory impairment was observed in patients with AD. The changes progress during the course of the disease. However, unlike verbal memory, olfactory memory is not significantly impaired in the prodromal stage of AD.

IntroductionCognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.MethodsIn the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus.ResultsAdministration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.DiscussionOur findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

ADHD is a typical neurodevelopmental disorder with a high prevalence rate. NSCs in the subventricular zone (SVZ) are closely related to neurodevelopmental disorder and can affect olfactory function by neurogenesis and migratory route. Although olfactory dysfunction is one of the symptoms of ADHD, the relevance of cells in the olfactory bulb derived from NSCs has not been studied. Therefore, we investigated olfactory memory and NSCs in Git1-deficient mice, under the ADHD model. Interestingly, only adult male G protein-coupled receptor kinase-interacting protein-1 (GIT1)-deficient (+/−, HE) mice showed impaired olfactory memory, suggesting sex and age dependence. We performed adult NSCs culture from the SVZ and observed distinct cell population in both sex and genotype. Taken together, our study suggests that the altered differentiation of NSCs in GIT1+/− mice can contribute to olfactory dysfunction in ADHD.

Abstract Background and objectives: This clinical trial aimed to evaluate the effects of two different inhalation anesthetic agents on postoperative olfactory memory and olfactory function in patients who underwent micro laryngeal surgery. Methods: This randomized prospective controlled study consisted of 102 consecutive patients with a voice disorder. The patients underwent micro laryngeal surgery for voice disorders under general anesthesia. Patients who did not meet inclusion criteria and/or declined to participate (n = 34) were excluded from the study. Patients were divided into two groups. Four patients from Group 1 and four patients from Group 2 were lost to follow-up. Group 1 (n = 30) received sevoflurane, and Group 2 (n = 30) received desflurane during anesthesia. We compared the results by performing the pre-op and post-op Connecticut Chemosensory Clinical Research Center Olfactory test. Results: Thirty-three patients (55%) were male and 27 (45%) were female. The mean age was 48.18 ± 13.88 years (range: 19‒70 years). Preoperative and postoperative olfactory functions did not show a significant difference within the groups postoperatively (p > 0.05). Preoperative and postoperative olfactory memory showed a significant decrease 3 hours after the surgery (p < 0.05). Conclusions: Olfactory functions and memory were not affected by desflurane in the early postoperative period. Although sevoflurane did not affect olfactory functions, it had a temporary negative effect on olfactory memory in the early postoperative period.

Multiple spaced trials of aversive differential conditioning can produce two independent long-term memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS–). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS–. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and -unpaired CS–, and be retrieved by either CS+ or CS–. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons, in which similar-amplitude long-term depression of responses to CS+ and CS– seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.

Active memory forgetting is a well-regulated biological process thought to be adaptive and to allow proper cognitive functions. Recent efforts have elucidated several molecular players involved in the regulation of olfactory forgetting in Drosophila, including the small G protein Rac1, the dopamine receptor DAMB, and the scaffold protein Scribble. Similarly, we recently reported that dopaminergic neurons mediate both learning- and forgetting-induced plasticity in the mushroom body output neuron MBON-γ2α′1. Two open questions remain: how does forgetting affect plasticity in other, highly plastic, mushroom body compartments and how do genes that regulate forgetting affect this cellular plasticity? Here, we show that forgetting reverses short-term synaptic depression induced by aversive conditioning in the highly plastic mushroom body output neuron MBON-γ1pedc>α/β. In addition, our results indicate that genetic tampering with normal forgetting by inhibition of small G protein Rac1 impairs restoration of depressed odor responses to learned odor by intrinsic forgetting through time passing and forgetting induced acutely by shock stimulation after conditioning or reversal learning. These data further indicate that some forms of forgetting truly erase physiological changes generated by memory encoding.

David C Dorman,1 Melanie L Foster,2 Katherine E Fernhoff,1 Paul R Hess2 1Department of Molecular and Biomedical Sciences, 2Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA Abstract: The scent detection prowess of dogs has prompted interest in their ability to detect cancer. The purpose of this study was to determine whether dogs could use olfactory cues to discriminate urine samples collected from dogs that did or did not have urinary tract transitional cell carcinoma (TCC), at a rate greater than chance. Dogs with previous scent training (n=4) were initially trained to distinguish between a single control and a single TCC-positive urine sample. All dogs acquired this task (mean =15±7.9 sessions; 20 trials/session). The next training phase used four additional control urine samples (n=5) while maintaining the one original TCC-positive urine sample. All dogs quickly acquired this task (mean =5.3±1.5 sessions). The last training phase used multiple control (n=4) and TCC-positive (n=6) urine samples to promote categorical training by the dogs. Only one dog was able to correctly distinguish multiple combinations of TCC-positive and control urine samples suggesting that it mastered categorical learning. The final study phase evaluated whether this dog would generalize this behavior to novel urine samples. However, during double-blind tests using two novel TCC-positive and six novel TCC-negative urine samples, this dog did not indicate canine TCC-positive cancer samples more frequently than expected by chance. Our study illustrates the need to consider canine olfactory memory and the use of double-blind methods to avoid erroneous conclusions regarding the ability of dogs to alert on specimens from canine cancer patients. Our results also suggest that sample storage, confounding odors, and other factors need to be considered in the design of future studies that evaluate the detection of canine cancers by scent detection dogs. Keywords: urinary tract cancer, cancer detection dogs, cancer odor, olfactory memory, multiple sample learning

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. Moreover, the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased complexity and restructuring of neural network structures, as well as the addition of new granule granule cells that aid in olfactory adaptation. Additionally, the manuscript underscores the importance of employing precise methodologies to elucidate the specific roles of adult neurogenesis amidst conflicting data and varying experimental paradigms. Understanding these processes is essential for gaining insights into the complexities of olfactory function and behavior.

Blindness can be a driving force behind a variety of changes in sensory systems. When vision is missing, other modalities and higher cognitive functions can become hyper-developed through a mechanism called sensory compensation. Overall, previous studies suggest that olfactory memory in blind people can be better than that of the sighted individuals. Better performance of blind individuals in other-sensory modalities was hypothesized to be a result of, among others, intense perceptual training. At the same time, if the superiority of blind people in olfactory abilities indeed results from training, their scores should not decrease with age to such an extent as among the sighted people. Here, this hypothesis was tested in a large sample of 94 blind individuals. Olfactory memory was assessed using the Test for Olfactory Memory, comprising episodic odor recognition (discriminating previously presented odors from new odors) and two forms of semantic memory (cued and free identification of odors). Regarding episodic olfactory memory, we observed an age-related decline in correct hits in blind participants, but an age-related increase in false alarms in sighted participants. Further, age moderated the between-group differences for correct hits, but the direction of the observed effect was contrary to our expectations. The difference between blind and sighted individuals younger than 40 years old was non-significant, but older sighted individuals outperformed their blind counterparts. In conclusion, we found no positive effect of visual impairment on olfactory memory. We suggest that daily perceptual training is not enough to increase olfactory memory function in blind people.

The aim of the present study was to evaluate the sensory assessments of identical cosmetic formulations with and without fragrance to investigate not only the acceptance but also how different fragrances affected their attributes, such as skin feel, tackiness and spreadability. Three gel and three cream formulations with and without two types of fragrance, fennel and sweet flowers, were assessed for various attributes. The presence and type of fragrance used affected the testers' perception of some attributes, showing that the influence of this component should not be disregarded. Apparently, a consumer's reaction to a cosmetic product is not only based on its efficacy but also on how its attributes are perceived, such as appearance, skin feel and smell.

There is evidence for both neurotoxic and neuroprotective roles of nitric oxide (NO) in the brain and changes in the expression of the neuronal isoform of nitric oxide synthase (nNOS) gene occur during aging. The current studies have investigated potential support for either a neurotoxic or neuroprotective role of NO derived from nNOS in the context of aging by comparing olfactory learning and locomotor function in young compared to old nNOS knockout (nNOS/-) and wildtype control mice. Tasks involving social recognition and olfactory conditioning paradigms showed that old nNOS-/-animals had improved retention of learning compared to similar aged wildtype controls. Young nNOS-/- animals showed superior reversal learning to wildtypes in a conditioned learning task, although their performance was weakened with age. Interestingly, whereas young nNOS-/- animals were impaired in long term memory for social odors compared to wildtype controls, in old animals this pattern was reversed, possibly indicating beneficial compensatory changes influencing olfactory memory may occur during aging in nNOS-/- animals. Possibly such compensatory changes may have involved increased NO from other NOS isoforms since the memory deficit in young nNOS-/-animals could be rescued by the NO-donor, molsidomine. Both nNOS-/- and wildtype animals showed an age-associated decline in locomotor activity although young nNOS-/- animals were significantly more active than wildtypes, possibly due to an increased interest in novelty. Overall our findings suggest that lack of NO release via nNOS may protect animals to some extent against age-associated cognitive decline in memory tasks typically involving olfactory and hippocampal regions, but not against declines in reversal learning or locomotor activity.