Direct excitation of mitral cells via activation of alpha1-noradrenergic receptors in rat olfactory bulb slices.
(33/262)
The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 microM), isoproterenol (Isop, 10 microM), and clonidine (3 microM), were used to test for the functional presence of alpha1-, beta-, and alpha2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)-evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 microM) induced an inward current (54 +/- 7 pA, n = 16) with an EC(50) of 4.7 microM. Both PE and Isop also produced inward currents (22 +/- 4 pA, n = 19, and 29 +/- 9 pA, n = 8, respectively), while clonidine produced no effect (n = 6). In the presence of TTX (1 microM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 microM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 microM, and (+/-)-2-amino-5-phosphonopentanoic acid (APV) 50 microM], the inward current induced by PE persisted (EC(50) = 9 microM), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca(2+) channel blockers, cadmium (100 microM) and nickel (100 microM). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPbetaS, indicating that the alpha1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (-52 mV) toward the upstate (-40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via alpha1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo. (+info)
Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals.
(34/262)
Olfactory receptor neurons of the nasal epithelium project via the olfactory nerve (ON) to the glomeruli of the main olfactory bulb, where they form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the olfactory bulb, and with juxtaglomerular interneurons. The glomerular layer contains one of the largest population of dopamine (DA) neurons in the brain, and DA in the olfactory bulb is found exclusively in juxtaglomerular neurons. D2 receptors, the predominant DA receptor subtype in the olfactory bulb, are found in the ON and glomerular layers, and are present on ON terminals. In the present study, field potential and single-unit recordings, as well as whole cell patch-clamp techniques, were used to investigate the role of DA and D2 receptors in glomerular synaptic processing in rat and mouse olfactory bulb slices. DA and D2 receptor agonists reduced ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells. Spontaneous and ON-evoked spiking of mitral cells was also reduced by DA and D2 agonists, and enhanced by D2 antagonists. DA did not produce measurable postsynaptic changes in juxtaglomerular cells, nor did it alter their responses to mitral/tufted cell inputs. DA also reduced 1) paired-pulse depression of ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells and 2) the amplitude and frequency of spontaneous, but not miniature, excitatory postsynaptic currents in juxtaglomerular cells. Taken together, these findings are consistent with the hypothesis that activation of D2 receptors presynaptically inhibits ON terminals. DA and D2 agonists had no effect in D2 receptor knockout mice, suggesting that D2 receptors are the only type of DA receptors that affect signal transmission from the ON to the rodent olfactory bulb. (+info)
The glucose transporter GLUT1 and the tight junction protein occludin in nasal olfactory mucosa.
(35/262)
The nervous cells in the brain and the peripheral nerves are isolated from the external environment by the blood-brain, blood-cerebrospinal fluid and blood-nerve barriers. The glucose transporter GLUT1 mediates the specific transfer of glucose across these barriers. The olfactory system is unique in that its sensory cells, olfactory receptor neurons, are embedded in the nasal olfactory epithelium and send their axons directly to the olfactory bulb of the brain. Only the apical parts of the olfactory receptor neurons are exposed to the lumen, and these serve as sensors for smell. Immunohistochemical examination showed that the tight junction protein occludin was present in the junctions of the olfactory epithelium. Endothelial cells in the blood vessels in the lamina propria of the olfactory mucosa were also positive for occludin. These observations suggest that the olfactory system is guarded from both the external environment and the blood. GLUT1 was abundant in these occludin-positive endothelial cells, suggesting that GLUT1 may serve in nourishing the cells of the olfactory system. Taken together, GLUT1 and occludin may serve as part of the machinery for the specific transfer of glucose in the olfactory system while preventing the non-specific entry of substances. (+info)
Response correlation maps of neurons in the mammalian olfactory bulb.
(36/262)
To define the relationship between glomerular activation patterns and neuronal olfactory responses in the main olfactory bulb, intracellular recordings were combined with optical imaging of intrinsic signals. Response correlation maps (RCMs) were constructed by correlating the fluctuations in membrane potential and firing rate during odorant presentations with patterns of glomerular activation. The RCMs indicated that mitral/tufted cells were excited by activation of a focal region surrounding their principal glomerulus and generally inhibited by activation of more distant regions. However, the structure of the RCMs and the relative contribution of excitatory and inhibitory glomerular input evolved and even changed sign during and after odorant application. These data suggest a dynamic center-surround organization of mitral/tufted cell receptive fields. (+info)
Relative neurotropism of a recombinant rhabdovirus expressing a green fluorescent envelope glycoprotein.
(37/262)
A new recombinant vesicular stomatitis virus (rVSV) that expresses green fluorescent protein (GFP) on the cytoplasmic domain of the VSV glycoprotein (G protein) was used in the mouse as a model for studying brain infections by a member of the Mononegavirales order that can cause permanent changes in behavior. After nasal administration, virus moved down the olfactory nerve, first to periglomerular cells, then past the mitral cell layer to granule cells, and finally to the subventricular zone. Eight days postinoculation, rVSV was eliminated from the olfactory bulb. Little sign of infection could be found outside the olfactory system, suggesting that anterograde or retrograde axonal transport of rVSV was an unlikely mechanism for movement of rVSV out of the bulb. When administered intracerebrally by microinjection, rVSV spread rapidly within the brain, with strong infection at the site of injection and at some specific periventricular regions of the brain, including the dorsal raphe, locus coeruleus, and midline thalamus; the ventricular system may play a key role in rapid rVSV dispersion within the brain. Thus, the lack of VSV movement out of the olfactory system was not due to the absence of potential for infections in other brain regions. In cultures of both mouse and human central nervous system (CNS) cells, rVSV inoculations resulted in productive infection, expression of the G-GFP fusion protein in the dendritic and somatic plasma membrane, and death of all neurons and glia, as detected by ethidium homodimer nuclear staining. Although considered a neurotropic virus, rVSV also infected heart, skin, and kidney cells in dispersed cultures. rVSV showed a preference for immature neurons in vitro, as shown by enhanced viral infection in developing hippocampal cultures and in the outer granule cell layer in slices of developing cerebellum. Together, these data suggest a relative affinity of rVSV for some neuronal types in the CNS, adding to our understanding of the long-lasting changes in rodent behavior found after transient VSV infection. (+info)
Olfactory acuity after total laryngectomy.
(38/262)
The olfactory acuity of 29 patients receiving laryngectomy was prospectively studied. The olfactory acuity was evaluated by Jet Stream Olfactometer (JSO) and Alinamin test preoperatively and at 3, 6 and 12 months postoperatively. The findings of nasal/olfactory mucosae were also observed by rigid endoscope. Based on the results of JSO, the averages of detection/recognition thresholds tended to increase 3 months postoperatively, then the averaged thresholds tended to decrease thereafter. There were significant differences between preoperative values and those 3 months after surgery, but there were no significant differences between preoperative values and these 6/12 months after surgery. Nasal respiratory mucosae observed 12 months after laryngectomy showed atrophic nasal mucosa in 11/14 patients. However, olfactory mucosae appeared normal in all of the patients observed. These results suggested that the function of the olfactory epithelium remained intact after laryngectomy. (+info)
Newborn with transverse facial cleft associated with polyhydramnios.
(39/262)
We describe here the case of a female newborn baby with a bilateral complete transverse facial cleft. Obstetrical ultrasound had revealed an increased amount of amniotic fluid from 28 weeks' gestation without fetal hydrops or congenital anomalies. A 1900-g baby girl born at 36 weeks' gestation presented with bilateral wide facial clefts with macrostomia, microphthalmia, nose, and auricular deformities. Her breathing was dependent on life support, which was discontinued 2 hours after birth. An autopsy revealed no congenital malformations in vital organs but the absence of the olfactory nerves. Polyhydramnios and respiratory arrest after birth were presumed to be due to central disintegration of swallowing and breathing, in this case with brain anomaly. (+info)
Synaptic actions on mitral and tufted cells elicited by olfactory nerve volleys in the rabbit.
(40/262)
1. A unitary study has been carried out of mitral and tufted cell responses to olfactory nerve volleys in the olfactory bulb of rabbits lightly anaesthetized with urethane-chloralose. 2. With volleys of different strengths, some mitral cells responded with a spike whose latency decreased considerably as the strength increased (elastic response); other cells responded at an invariant latency (inelastic response). The former may reflect diffuse olfactory nerve inputs to the dendritic tufts in the olfactory glomeruli, while tha latter may reflect input from discrete bundles of fibres. 3. The shortest spike latencies are consistent with monosynaptic excitation by the olfactory nerves; longer latencies may be due to longer pathways through the nerves, or polysynaptic pathways within the glomerular layer. 4. Facilitation, in terms of lower threshold and shorter spike latency, was found when testing with paired volleys of weak intensity at relatively short intervals (less than 40 msec). Suppression, in terms of raised threshold, longer latency and briefer repetitive discharges, was found at intervals up to several hundred msec. The facilitation and suppression are consistent with the hypothesis of synaptic excitation and inhibition, respectively, mediated through interneurones in the olfactory bulb. 5. Presumed tufted cells were similar in response properties to identified mitral cells. 6. Intracellular recordings revealed long-lasting hyperpolarization and in some cases, an initial depolarization leading to spike initiation, in response to an olfactory nerve volley. (+info)