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1.
Nat Commun ; 9(1): 2887, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-30038239

RESUMO

In many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs), determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our findings demonstrate that olfactory thresholds are set by the single highest affinity receptor and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.


Assuntos
Odorantes , Receptores Acoplados a Proteínas G/fisiologia , Receptores Odorantes/fisiologia , Aminas/química , Animais , Comportamento Animal , Deleção de Genes , Genótipo , Ligantes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Bulbo Olfatório/fisiologia , Neurônios Receptores Olfatórios/fisiologia , Psicometria , Receptores Acoplados a Proteínas G/genética , Receptores Odorantes/genética , Células Receptoras Sensoriais/fisiologia , Olfato , Especificidade da Espécie
2.
Sci Rep ; 8(1): 901, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343813

RESUMO

Extrinsic control of single neurons and neuronal populations is a powerful approach for understanding how neural circuits function. Adding new thermogenetic tools to existing optogenetic and other forms of intervention will increase the complexity of questions that can be addressed. A good candidate for developing new thermogenetic tools is the Drosophila gustatory receptor family, which has been implicated in high-temperature avoidance behavior. We examined the five members of the Gr28b gene cluster for temperature-dependent properties via three approaches: biophysical characterization in Xenopus oocytes, functional calcium imaging in Drosophila motor neurons, and behavioral assays in adult Drosophila. Our results show that Gr28bD expression in Xenopus oocytes produces a non-specific cationic current that is activated by elevated temperatures. This current is non-inactivating and non-voltage dependent. When expressed in Drosophila motor neurons, Gr28bD can be used to change the firing pattern of individual cells in a temperature-dependent fashion. Finally, we show that pan-neuronal or motor neuron expression of Gr28bD can be used to alter fruit fly behavior with elevated temperatures. Together, these results validate the potential of the Gr28bD gene as a founding member of a new class of thermogenetic tools.


Assuntos
Cátions/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Receptores de Superfície Celular/metabolismo , Canais de Cátion TRPC/metabolismo , Termogênese/fisiologia , Animais , Animais Geneticamente Modificados/metabolismo , Aprendizagem da Esquiva/fisiologia , Locomoção/fisiologia , Neurônios/metabolismo , Oócitos/metabolismo , Optogenética/métodos , Temperatura , Xenopus/metabolismo
3.
J Neurosci Res ; 95(5): 1194-1203, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28105691

RESUMO

Fetal alcohol exposure can cause Fetal Alcohol Spectrum Disorders (FASD), completely preventable developmental disabilities characterized by permanent birth defects. However, specific gestational timing when developing organs are most sensitive to alcohol exposure is unclear. In this study, we examined the temporal effects of embryonic alcohol exposure on octavolateral organs in zebrafish (Danio rerio), including inner ears and lateral line neuromasts that function in hearing, balance, and hydrodynamic detection, respectively. To determine an alcohol-sensitive period in the first 24 hours post fertilization (hpf), Et(krt4:EGFP)sqet4 zebrafish that express green fluorescent protein in sensory hair cells were treated in 2% alcohol for 2, 3, and 5-hours. Octavolateral organs of control and alcohol-exposed larvae were examined at 3, 5, and 7 days post fertilization (dpf). Using confocal and light microscopy, we found that alcohol-exposed larvae had significantly smaller otic vesicles and saccular otoliths than control larvae at 3 dpf. Only alcohol-exposed larvae from 12-17 hpf had smaller otic vesicles at 5 dpf, smaller saccular otoliths at 7 dpf and fewer saccular hair cells, neuromasts and hair cells per neuromast at 3 dpf. In addition, auditory function was assessed by microphonic potential recordings from inner ear hair cells in response to 200-Hz stimulation. Hearing sensitivity was reduced for alcohol-exposed larvae from 7-12 and 12-17 hpf. Our results show that 12-17 hpf is an alcohol-sensitive time window when morphology and function of zebrafish octavolateral organs are most vulnerable to alcohol exposure. This study implies that embryonic alcohol exposure timing during early development can influence severity of hearing deficits. © 2017 Wiley Periodicals, Inc.


Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Orelha Interna/efeitos dos fármacos , Etanol/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Audição/efeitos dos fármacos , Fatores Etários , Análise de Variância , Animais , Animais Geneticamente Modificados , Orelha Interna/embriologia , Embrião não Mamífero , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Audição/fisiologia , Perda Auditiva/induzido quimicamente , Queratina-4/genética , Queratina-4/metabolismo , Larva/efeitos dos fármacos , Sistema da Linha Lateral/efeitos dos fármacos , Sistema da Linha Lateral/embriologia , Peixe-Zebra
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