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1.
Nat Neurosci ; 25(9): 1119, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35902651
2.
Proc Natl Acad Sci U S A ; 111(47): 16931-6, 2014 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-25385630

RESUMEN

The piriform cortex (PCX) is the largest component of the olfactory cortex and is hypothesized to be the locus of odor object formation. The distributed odorant representation found in PCX contrasts sharply with the topographical representation seen in other primary sensory cortices, making it difficult to test this view. Recent work in PCX has focused on functional characteristics of these distributed afferent and association fiber systems. However, information regarding the efferent projections of PCX and how those may be involved in odor representation and object recognition has been largely ignored. To investigate this aspect of PCX, we have used the efferent pathway from mouse PCX to the orbitofrontal cortex (OFC). Using double fluorescent retrograde tracing, we identified the output neurons (OPNs) of the PCX that project to two subdivisions of the OFC, the agranular insula and the lateral orbitofrontal cortex (AI-OPNs and LO-OPNs, respectively). We found that both AI-OPNs and LO-OPNs showed a distinct spatial topography within the PCX and fewer than 10% projected to both the AI and the LO as judged by double-labeling. These data revealed that the efferent component of the PCX may be topographically organized. Further, these data suggest a model for functional organization of the PCX in which the OPNs are grouped into parallel output circuits that provide olfactory information to different higher centers. The distributed afferent input from the olfactory bulb and the local PCX association circuits would then ensure a complete olfactory representation, pattern recognition capability, and neuroplasticity in each efferent circuit.


Asunto(s)
Corteza Piriforme/anatomía & histología , Células Receptoras Sensoriales/citología , Animales , Ratones , Corteza Piriforme/citología
3.
Front Neurosci ; 8: 182, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25018692

RESUMEN

Neurogenesis continues well beyond embryonic and early postnatal ages in three areas of the nervous system. The subgranular zone supplies new neurons to the dentate gyrus of the hippocampus. The subventricular zone supplies new interneurons to the olfactory bulb, and the olfactory neuroepithelia generate new excitatory sensory neurons that send their axons to the olfactory bulb. The latter two areas are of particular interest as they contribute new neurons to both ends of a first-level circuit governing olfactory perception. The vomeronasal organ and the main olfactory epithelium comprise the primary peripheral olfactory epithelia. These anatomically distinct areas share common features, as each exhibits extensive neurogenesis well beyond the juvenile phase of development. Here we will discuss the effect of age on the structural and functional significance of neurogenesis in the vomeronasal and olfactory epithelia, from juvenile to advanced adult ages, in several common model systems. We will next discuss how age affects the regenerative capacity of these neural stem cells in response to injury. Finally, we will consider the integration of newborn neurons into an existing circuit as it is modified by the age of the animal.

4.
Proc Natl Acad Sci U S A ; 110(11): 4410-5, 2013 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-23401498

RESUMEN

Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.


Asunto(s)
Presión Sanguínea/fisiología , Intestinos/microbiología , Riñón/metabolismo , Metagenoma/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Receptores Odorantes/metabolismo , Renina/metabolismo , Transducción de Señal/fisiología , Animales , Biomasa , Presión Sanguínea/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Hipertensión/genética , Hipertensión/metabolismo , Hipertensión/microbiología , Mucosa Intestinal/metabolismo , Ratones , Ratones Noqueados , Propionatos/metabolismo , Propionatos/farmacología , Receptores Acoplados a Proteínas G/genética , Receptores Odorantes/genética , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
5.
Neurobiol Aging ; 34(7): 1873-81, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23419702

RESUMEN

Throughout life the subventricular zone (SVZ) is a source of new olfactory bulb (OB) interneurons. From the SVZ, neuroblasts migrate tangentially through the rostral migratory stream (RMS), a restricted route approximately 5 mm long in mice, reaching the OB within 10-14 days. Within the OB, neuroblasts migrate radially to the granule and glomerular layers where they differentiate into granule and periglomerular (PG) cells and integrate into existing synaptic circuits. SVZ neurogenesis decreases with age, and might be a factor in age-related olfactory deficits. However, the effect of aging on the RMS and on the differentiation of interneuron subpopulations remains poorly understood. Here, we examine RMS cytoarchitecture, neuroblast proliferation and clearance from the RMS, and PG cell subpopulations at 6, 12, 18, and 23 months of age. We find that aging affects the area occupied by newly generated cells within the RMS and regional proliferation, and the clearance of neuroblasts from the RMS and PG cell subpopulations and distribution remain stable.


Asunto(s)
Envejecimiento/fisiología , Movimiento Celular/fisiología , Ventrículos Cerebrales/fisiología , Neurogénesis/fisiología , Bulbo Olfatorio/fisiología , Animales , Proliferación Celular , Ventrículos Cerebrales/citología , Ratones , Ratones Endogámicos C57BL , Bulbo Olfatorio/citología
6.
Nat Methods ; 8(8): 684-90, 2011 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-21725301

RESUMEN

Membrane proteins are a large, diverse group of proteins, serving a multitude of cellular functions. They are difficult to study because of their requirement of a lipid membrane for function. Here we show that two-photon polarization microscopy can take advantage of the cell membrane requirement to yield insights into membrane protein structure and function, in living cells and organisms. The technique allows sensitive imaging of G-protein activation, changes in intracellular calcium concentration and other processes, and is not limited to membrane proteins. Conveniently, many suitable probes for two-photon polarization microscopy already exist.


Asunto(s)
Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/ultraestructura , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Microscopía de Polarización/métodos , Conformación Proteica , Relación Estructura-Actividad
7.
J Neurosci ; 30(30): 10067-75, 2010 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-20668191

RESUMEN

As odorant receptors (ORs) are thought to be critical determinants of olfactory sensory neuron (OSN) axon targeting and organization, we examined the spatiotemporal onset of mice ORs expression from the differentiation of OSNs in the olfactory placode to an aging olfactory epithelium. ORs were first detected in the placode at embryonic day 9 (E9), at the onset of OSN differentiation but before axon extension. By E13, 22 of 23 ORs were expressed. Onset of individual OR expression was diverse; levels and patterns of expression were unique for each OR. Regional distribution of ORs within zones of the olfactory epithelium appeared stable across development; adult-like patterns were observed by E13. Finally, analysis of OR expression and chromosomal location suggests that ORs are not stochastically expressed; they show evidence of coordinated expression. Collectively, these studies demonstrate that ORs are not equally represented in the "olfactome" across an animal's lifespan.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Bulbo Olfatorio/citología , Neuronas Receptoras Olfatorias/metabolismo , Receptores Odorantes/metabolismo , Algoritmos , Animales , Animales Recién Nacidos , Diferenciación Celular/fisiología , Mapeo Cromosómico/métodos , Embrión de Mamíferos , Ratones , Ratones Endogámicos C57BL , Análisis por Micromatrices/métodos , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Bulbo Olfatorio/embriología , Bulbo Olfatorio/crecimiento & desarrollo , Receptores Odorantes/genética , Tubulina (Proteína)/metabolismo
9.
Mol Cell Neurosci ; 38(4): 518-25, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18571430

RESUMEN

Olfactory sensory neurons (OSNs) represent a unique population of neurons in which death and regeneration are ongoing throughout adulthood, a feature that makes them an attractive model cell type for the investigation of neuronal death. However, the mechanism by which OSNs die remains elusive. Therefore, we developed a culture system for studying pathways involved in OSN death. Here, we show that inhibition of transcription or translation, by actinomycin D or cycloheximide, respectively, suppresses pathways leading to death, prolonging the survival of OSNs in culture. We discovered that caspase activity and jun N-terminal kinase (JNK) signaling both play a role in OSN death, and inhibition of JNK activity suppresses effector caspase (caspase-3) activation. Results from studies in culture were confirmed in vivo, in a mouse bulbectomy-induced OSN death model. These findings provide new insights into the nature of OSN death and a means of studying OSNs in vitro.


Asunto(s)
Proteínas Quinasas JNK Activadas por Mitógenos/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas/enzimología , Neuronas Receptoras Olfatorias/enzimología , Animales , Muerte Celular/fisiología , Células Cultivadas , Ratones , Bulbo Olfatorio/enzimología
10.
Proc Natl Acad Sci U S A ; 101(39): 14168-73, 2004 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-15377787

RESUMEN

The large number of olfactory receptor genes necessitates high throughput methods to analyze their expression patterns. We have therefore designed a high-density oligonucleotide array containing all known mouse olfactory receptor (OR) and V1R vomeronasal receptor genes. This custom array detected a large number of receptor genes, demonstrating specific expression in the olfactory sensory epithelium for approximately 800 OR genes previously designated as ORs based solely on genomic sequences. The array also enabled us to monitor the spatial and temporal distribution of gene expression for the entire OR family. Interestingly, OR genes showing spatially segregated expression patterns were also segregated on the chromosomes. This correlation between genomic location and spatial expression provides unique insights about the regulation of this large family of genes.


Asunto(s)
Mucosa Olfatoria/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Receptores Odorantes/genética , Factores de Edad , Animales , Cromosomas/genética , Análisis por Conglomerados , Perfilación de la Expresión Génica , Genoma , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos , Mucosa Olfatoria/fisiología , Receptores Odorantes/biosíntesis , Testículo/metabolismo , Órgano Vomeronasal/metabolismo
11.
Genomics ; 81(5): 443-56, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12706103

RESUMEN

We applied an automatic and unsupervised system to a nearly complete database of mammalian odor receptor genes. The generated motifs and gene classification were subjected to extensive and systematic downstream analysis to obtain biological insights. Two major results from this analysis were: (1) a map of sequence motifs that may correlate with function and (2) the corresponding receptor classes in which members of each class are likely to share specific functions. We have discovered motifs that have been implicated in structural integrity and posttranslational modification, as well as motifs very likely to be directly involved in ligand binding. We further propose a combinatorial molecular hypothesis, based on unique combinations of the observed motifs, that provides a foundation for understanding the generation of a large number of ligand binding sites.


Asunto(s)
Receptores Odorantes/metabolismo , Secuencias de Aminoácidos , Animales , Sitios de Unión , Biología Computacional , Bases de Datos Genéticas , Humanos , Ratones , Procesamiento Proteico-Postraduccional , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Receptores Odorantes/clasificación , Receptores Odorantes/genética
12.
Neuron ; 34(1): 5-6, 2002 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-11931735

RESUMEN

Dendrodendritic inhibition between mitral and granule cells in the olfactory bulb is thought to play an important role in olfactory discrimination. In this issue of Neuron, explore the propagation of action potentials along the secondary dendrites of mitral cells and their modulation by dendrodendritic inhibition.


Asunto(s)
Potenciales de Acción/fisiología , Animales , Dendritas/fisiología , Humanos , Bulbo Olfatorio/fisiología , Neuronas Receptoras Olfatorias/fisiología , Sinapsis/fisiología
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