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National Science Review May 2024Octopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various...
Octopamine (OA), analogous to norepinephrine in vertebrates, is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions, including olfactory associative learning. However, the spatial and temporal dynamics of OA remain poorly understood due to limitations associated with the currently available methods used to detect it. To overcome these limitations, we developed a genetically encoded GPCR activation-based (GRAB) OA sensor called GRAB. This sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular OA. Using GRAB, we monitored OA release in the mushroom body (MB), the fly's learning center, and found that OA is released in response to both odor and shock stimuli in an aversive learning model. This OA release requires acetylcholine (ACh) released from Kenyon cells, signaling via nicotinic ACh receptors. Finally, we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octβ1R in dopaminergic neurons, leading to alterations in synaptic plasticity within the MB. Thus, our new GRAB sensor can be used to monitor OA release in real time under physiological conditions, providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.
PubMed: 38798960
DOI: 10.1093/nsr/nwae112 -
The Journal of Experimental Medicine Jun 2024Irene Salinas is a professor in the Department of Biology, University of New Mexico. Her lab uses multiple animal models to study nasal immunity and neuroimmune...
Irene Salinas is a professor in the Department of Biology, University of New Mexico. Her lab uses multiple animal models to study nasal immunity and neuroimmune interactions in the olfactory-central nervous system axis in response to microorganisms. We recently spoke with Irene about her current work, her diversity, equity, and inclusion (DEI) work, and how her leadership style has changed over the years.
PubMed: 38771656
DOI: 10.1084/jem.20240813 -
ArXiv May 2024The integration of neural representations in the two hemispheres is an important problem in neuroscience. Recent experiments revealed that odor responses in cortical...
The integration of neural representations in the two hemispheres is an important problem in neuroscience. Recent experiments revealed that odor responses in cortical neurons driven by separate stimulation of the two nostrils are highly correlated. This bilateral alignment points to structured inter-hemispheric connections, but detailed mechanism remains unclear. Here, we hypothesized that continuous exposure to environmental odors shapes these projections and modeled it as online learning with local Hebbian rule. We found that Hebbian learning with sparse connections achieves bilateral alignment, exhibiting a linear trade-off between speed and accuracy. We identified an inverse scaling relationship between the number of cortical neurons and the inter-hemispheric projection density required for desired alignment accuracy, i.e., more cortical neurons allow sparser inter-hemispheric projections. We next compared the alignment performance of local Hebbian rule and the global stochastic-gradient-descent (SGD) learning for artificial neural networks. We found that although SGD leads to the same alignment accuracy with modestly sparser connectivity, the same inverse scaling relation holds. We showed that their similar performance originates from the fact that the update vectors of the two learning rules align significantly throughout the learning process. This insight may inspire efficient sparse local learning algorithms for more complex problems.
PubMed: 38764587
DOI: No ID Found -
Scientific Reports May 2024The phenomenon of contagious itch, observed in both humans and rodents, remains a topic of ongoing debate concerning its modulators and underlying pathways. This study...
The phenomenon of contagious itch, observed in both humans and rodents, remains a topic of ongoing debate concerning its modulators and underlying pathways. This study delves into the relationship between contagious itch and familiar olfactory cues, a non-visual factor contributing to this intriguing behavior. Our findings showed that contagious itch in observer mice occurs during physical interaction with the cagemate itch-demonstrator but not with a stranger demonstrator or in a non-physical encounter condition. Notably, itch-experienced observer mice displayed an increased contagious itch behavior, highlighting the relevance of itch-associated memory in this phenomenon. Furthermore, anosmic observer mice, whether itch-naïve or itch-experienced, displayed no contagious itch behavior. These results demonstrate that the familiar olfactory cues, specifically cagemate body odors, are required for contagious itch behaviors in mice. In line with these behavioral findings, our study reveals increased activity in brain regions associated with olfaction, emotion, and memory during contagious itch, including the olfactory bulb, the amygdala, the hypothalamus, and the hippocampus, with this activity diminished in anosmic mice. In conclusion, our study unveils the critical role of familiar olfactory cues in driving contagious itch in mice, shedding light on the interplay between social factors, sensory perception, and memory in this phenomenon.
Topics: Animals; Pruritus; Mice; Cues; Smell; Male; Behavior, Animal; Interpersonal Relations; Mice, Inbred C57BL; Odorants; Olfactory Bulb; Brain
PubMed: 38760368
DOI: 10.1038/s41598-024-61078-3 -
Alzheimer's & Dementia : the Journal of... Jun 2024Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial...
BACKGROUND
Compromised autophagy, including impaired mitophagy and lysosomal function, plays pivotal roles in Alzheimer's disease (AD). Urolithin A (UA) is a gut microbial metabolite of ellagic acid that stimulates mitophagy. The effects of UA's long-term treatment of AD and mechanisms of action are unknown.
METHODS
We addressed these questions in three mouse models of AD with behavioral, electrophysiological, biochemical, and bioinformatic approaches.
RESULTS
Long-term UA treatment significantly improved learning, memory, and olfactory function in different AD transgenic mice. UA also reduced amyloid beta (Aβ) and tau pathologies and enhanced long-term potentiation. UA induced mitophagy via increasing lysosomal functions. UA improved cellular lysosomal function and normalized lysosomal cathepsins, primarily cathepsin Z, to restore lysosomal function in AD, indicating the critical role of cathepsins in UA-induced therapeutic effects on AD.
CONCLUSIONS
Our study highlights the importance of lysosomal dysfunction in AD etiology and points to the high translational potential of UA.
HIGHLIGHTS
Long-term urolithin A (UA) treatment improved learning, memory, and olfactory function in Alzheimer's disease (AD) mice. UA restored lysosomal functions in part by regulating cathepsin Z (Ctsz) protein. UA modulates immune responses and AD-specific pathophysiological pathways.
Topics: Alzheimer Disease; Animals; Coumarins; Lysosomes; Mice; Mice, Transgenic; Disease Models, Animal; Mitophagy; Amyloid beta-Peptides; Cognition
PubMed: 38753870
DOI: 10.1002/alz.13847 -
Nature May 2024Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions. However,...
Working memory, the process through which information is transiently maintained and manipulated over a brief period, is essential for most cognitive functions. However, the mechanisms underlying the generation and evolution of working-memory neuronal representations at the population level over long timescales remain unclear. Here, to identify these mechanisms, we trained head-fixed mice to perform an olfactory delayed-association task in which the mice made decisions depending on the sequential identity of two odours separated by a 5 s delay. Optogenetic inhibition of secondary motor neurons during the late-delay and choice epochs strongly impaired the task performance of the mice. Mesoscopic calcium imaging of large neuronal populations of the secondary motor cortex (M2), retrosplenial cortex (RSA) and primary motor cortex (M1) showed that many late-delay-epoch-selective neurons emerged in M2 as the mice learned the task. Working-memory late-delay decoding accuracy substantially improved in the M2, but not in the M1 or RSA, as the mice became experts. During the early expert phase, working-memory representations during the late-delay epoch drifted across days, while the stimulus and choice representations stabilized. In contrast to single-plane layer 2/3 (L2/3) imaging, simultaneous volumetric calcium imaging of up to 73,307 M2 neurons, which included superficial L5 neurons, also revealed stabilization of late-delay working-memory representations with continued practice. Thus, delay- and choice-related activities that are essential for working-memory performance drift during learning and stabilize only after several days of expert performance.
Topics: Animals; Female; Male; Mice; Calcium; Choice Behavior; Memory Consolidation; Memory, Short-Term; Mice, Inbred C57BL; Motor Cortex; Motor Neurons; Odorants; Optogenetics; Practice, Psychological; Psychomotor Performance; Smell; Time Factors
PubMed: 38750359
DOI: 10.1038/s41586-024-07425-w -
PloS One 2024In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For...
In nature, animals must navigate to forage according to their sensory inputs. Different species use different sensory modalities to locate food efficiently. For teleosts, food emits visual, mechanical, chemical, and/or possibly weak-electrical signals, which can be detected by optic, auditory/lateral line, and olfactory/taste buds sensory systems. However, how fish respond to and use different sensory inputs when locating food, as well as the evolution of these sensory modalities, remain unclear. We examined the Mexican tetra, Astyanax mexicanus, which is composed of two different morphs: a sighted riverine (surface fish) and a blind cave morph (cavefish). Compared with surface fish, cavefish have enhanced non-visual sensory systems, including the mechanosensory lateral line system, chemical sensors comprising the olfactory system and taste buds, and the auditory system to help navigate toward food sources. We tested how visual, chemical, and mechanical stimuli evoke food-seeking behavior. In contrast to our expectations, both surface fish and cavefish did not follow a gradient of chemical stimulus (food extract) but used it as a cue for the ambient existence of food. Surface fish followed visual cues (red plastic beads and food pellets), but, in the dark, were likely to rely on mechanosensors-the lateral line and/or tactile sensor-as cavefish did. Our results indicate cavefish used a similar sensory modality to surface fish in the dark, while affinity levels to stimuli were higher in cavefish. In addition, cavefish evolved an extended circling strategy to forage, which may yield a higher chance to capture food by swimming-by the food multiple times instead of once through zigzag motion. In summary, we propose that ancestors of cavefish, similar to the modern surface fish, evolved extended food-seeking behaviors, including circling motion, to adapt to the dark.
Topics: Animals; Feeding Behavior; Characidae; Biological Evolution; Caves; Cues; Blindness
PubMed: 38748713
DOI: 10.1371/journal.pone.0300793 -
Frontiers in Endocrinology 2024The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish...
The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish species remains limited due to their diversity and the scarcity of common biomarkers. In the present study, four major brain parts, the telencephalon, diencephalon, mesencephalon and rhombencephalon, were isolated in largemouth bass, . Within these parts, nine brain regions and 74 nuclei were further identified through morphological and cytoarchitectonic analysis. Transcriptome analysis revealed a total of 7153 region-highly expressed genes and 176 region-specifically expressed genes. Genes related to growth, reproduction, emotion, learning, and memory were significantly overexpressed in the olfactory bulb and telencephalon (OBT). Feeding and stress-related genes were in the hypothalamus (Hy). Visual system-related genes were predominantly enriched in the optic tectum (OT), while vision and hearing-related genes were widely expressed in the cerebellum (Ce) region. Sensory input and motor output-related genes were in the medulla oblongata (Mo). Osmoregulation, stress response, sleep/wake cycles, and reproduction-related genes were highly expressed in the remaining brain (RB). Three candidate marker genes were further identified for each brain regions, such as neuropeptide FF () for OBT, pro-melanin-concentrating hormone () for Hy, vesicular inhibitory amino acid transporter () for OT, excitatory amino acid transporter 1 () for Ce, peripherin () for Mo, and isotocin neurophysin () for RB. Additionally, the distribution of seven neurotransmitter-type neurons and five types of non-neuronal cells across different brain regions were analyzed by examining the expression of their marker genes. Notably, marker genes for glutamatergic and GABAergic neurons showed the highest expression levels across all brain regions. Similarly, the marker gene for radial astrocytes exhibited high expression compared to other markers, while those for microglia were the least expressed. Overall, our results provide a comprehensive overview of the structural and functional characteristics of distinct brain regions in the largemouth bass, which offers a valuable resource for understanding the role of central nervous system in regulating physiological processes in teleost.
Topics: Animals; Bass; Biomarkers; Brain; Neurons; Gene Expression Profiling; Transcriptome; Telencephalon
PubMed: 38745953
DOI: 10.3389/fendo.2024.1385575 -
Frontiers in Neuroscience 2024Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may...
Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IA strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the swing speed and step sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent non-motor symptoms that emerge in the early stages of dopaminergic neuron degeneration.
PubMed: 38745938
DOI: 10.3389/fnins.2024.1375265 -
BioRxiv : the Preprint Server For... Apr 2024In brain regions featuring ongoing plasticity, the task of quickly encoding new information without overwriting old memories presents a significant challenge. In the...
In brain regions featuring ongoing plasticity, the task of quickly encoding new information without overwriting old memories presents a significant challenge. In the rodent olfactory bulb, which is renowned for substantial structural plasticity driven by adult neurogenesis and persistent turnover of dendritic spines, we show that such plasticity is vital to overcoming this flexibility-stability dilemma. To do so, we develop a computational model for structural plasticity in the olfactory bulb and show that the maturation of adult-born neurons facilitates the abilities to learn quickly and forget slowly. Particularly important to achieve this goal are the transient enhancement of the plasticity, excitability, and susceptibility to apoptosis that characterizes young neurons. The model captures many experimental observations and makes a number of testable predictions. Overall, it identifies memory consolidation as an important role of adult neurogenesis in olfaction and exemplifies how the brain can maintain stable memories despite ongoing extensive plasticity.
PubMed: 38737721
DOI: 10.1101/2024.03.03.583153