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1.
J Neurosci ; 42(26): 5212-5228, 2022 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-35610046

RESUMEN

Activity in the dorsal vagal complex (DVC) is essential to gastric motility regulation. We and others have previously shown that this activity is greatly influenced by local GABAergic signaling, primarily because of somatostatin (SST)-expressing GABAergic neurons. To further understand the network dynamics associated with gastric motility control in the DVC, we focused on another neuron prominently distributed in this complex, neuropeptide-Y (NPY) neurons. However, the effect of these neurons on gastric motility remains unknown. Here, we investigate the anatomic and functional characteristics of the NPY neurons in the nucleus tractus solitarius (NTS) and their interactions with SST neurons using transgenic mice of both sexes. We sought to determine whether NPY neurons influence the activity of gastric-projecting neurons, synaptically interact with SST neurons, and affect end-organ function. Our results using combined neuroanatomy and optogenetic in vitro and in vivo show that NPY neurons are part of the gastric vagal circuit as they are trans-synaptically labeled by a viral tracer from the gastric antrum, are primarily excitatory as optogenetic activation of these neurons evoke EPSCs in gastric-antrum-projecting neurons, are functionally coupled to each other and reciprocally connected to SST neurons, whose stimulation has a potent inhibitory effect on the action potential firing of the NPY neurons, and affect gastric tone and motility as reflected by their robust optogenetic response in vivo. These findings indicate that interacting NPY and SST neurons are integral to the network that controls vagal transmission to the stomach.SIGNIFICANCE STATEMENT The brainstem neurons in the dorsal nuclear complex are essential for regulating vagus nerve activity that affects the stomach via tone and motility. Two distinct nonoverlapping populations of predominantly excitatory NPY neurons and predominantly inhibitory SST neurons form reciprocal connections with each other in the NTS and with premotor neurons in the dorsal motor nucleus of the vagus to control gastric mechanics. Light activation and inhibition of NTS NPY neurons increased and decreased gastric motility, respectively, whereas both activation and inhibition of NTS SST neurons enhanced gastric motility.


Asunto(s)
Tronco Encefálico , Estómago , Animales , Tronco Encefálico/fisiología , Femenino , Neuronas GABAérgicas/fisiología , Masculino , Ratones , Neuropéptido Y/farmacología , Ratas , Ratas Sprague-Dawley , Núcleo Solitario/fisiología , Estómago/inervación , Nervio Vago/fisiología
2.
Front Mol Neurosci ; 16: 1253669, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38025261

RESUMEN

The homeostatic modulation of synaptic transmission is an evolutionarily conserved mechanism that is critical for stabilizing the nervous system. At the Drosophila neuromuscular junction (NMJ), presynaptic homeostatic potentiation (PHP) compensates for impairments in postsynaptic glutamate receptors due to pharmacological blockade or genetic deletion. During PHP, there is an increase in presynaptic neurotransmitter release, counteracting postsynaptic changes and restoring excitation to baseline levels. Previous studies have shown that α2δ-3, an auxiliary subunit of voltage-gated calcium channels (VGCCs), is essential for both the rapid induction and sustained expression of PHP at the Drosophila NMJ. However, the molecular mechanisms by which α2δ-3 regulates neurotransmitter release during PHP remain to be elucidated. In this study, we utilized electrophysiological, confocal imaging, and super-resolution imaging approaches to explore how α2δ-3 regulates synaptic transmission during PHP. Our findings suggest that α2δ-3 governs PHP by controlling the localization of the calcium channel pore-forming α1 subunit at presynaptic release sites, or active zones. Moreover, we examined the role of two structural domains within α2δ-3 in regulating neurotransmitter release and calcium channel localization. Our results highlight that these domains in α2δ-3 serve distinct functions in controlling synaptic transmission and presynaptic calcium channel abundance, at baseline in the absence of perturbations and during PHP. In summary, our research offers compelling evidence that α2δ-3 is an indispensable signaling component for controlling calcium channel trafficking and stabilization in homeostatic plasticity.

4.
Innov Aging ; 4(2): igaa011, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32382662

RESUMEN

BACKGROUND AND OBJECTIVES: "Aging in place" is commonly defined as the ability to remain living safely and independently for as long as possible either in the home or community of one's choosing. Yet, the literature indicates that older adults prefer to remain specifically in their own homes. Homesharing, an innovative exchange-based housing approach, is a means by which older adults can obtain additional income, companionship, and assistance by renting out a room to a home seeker, potentially increasing capacity to remain living independently in their homes. But what is known about their experiences of homesharing? RESEARCH DESIGN AND METHODS: A scoping review was conducted to map and consolidate the literature related to the experience of homeshare participation for adults aged 55 and older published from 1989 to 2018. Fifteen databases were searched, including 3 medical, 5 social science, and 7 gray literature databases. Following abstract and full-text review, 6 sources were retained for study inclusion. Thematic content analysis was used to identify major themes. RESULTS: Within included studies, 4 major themes were identified: (i) benefits of homeshare participation for older adults; (ii) challenges of participating in homeshare for older adults; (iii) intergenerational engagement as social exchange; and (iv) the key role of agency facilitation. DISCUSSION AND IMPLICATIONS: Findings were used to derive practice, policy, and research implications. By focusing on older adults and the ways homesharing impacts their lives, we can better determine the viability of homeshare as a means for improving and prolonging experiences of living at home.

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