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ini
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut; and NeuroImaging Cluster, Marine Biological Laboratory, Woods Hole, Massachusetts
Submitted 1 September 2005; accepted in final form 21 November 2005
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Treloar et al. 2002). An odorant typically binds to many receptor proteins with different affinities and thus at moderate concentrations can activate a substantial subset of all glomeruli (Meister and Bonhoeffer 2001; Rubin and Katz 1999; Wachowiak and Cohen 2001). One of the functions of the olfactory bulb may be to reduce the extent of this rather widespread activation before transmitting the information to higher olfactory centers (Laurent 1999; Perez-Orive et al. 2002).
Considerable evidence shows that the mitral cell output activity differs in several dimensions from the olfactory sensory neuron input (e.g., Kay and Laurent 1999). Two circuits have been studied in vitro that could perform center-surround inhibition in the olfactory bulb: one acting through the classical reciprocal synapses between granule cells and the lateral dendrites of mitral cells (Rall et al. 1966) and the other between glomeruli (Aungst et al. 2003). Both these circuits can directly modify mitral cell output, the former by acting onto their basal dendrites, the latter by acting on the tuft of the apical dendrite inside the glomerulus. The later circuit could, however, also presynaptically inhibit neurotransmitter release from the olfactory receptor axon terminals.
From experiments in vitro it is known that synaptic transmission from olfactory receptor neurons can be modulated by presynaptic GABAB and dopamine D2 receptors (Duchamp-Viret et al. 2002; Ennis et al. 2001; Nickell et al. 1994; Wachowiak and Cohen 1999; Wachowiak et al. 2005). In vertebrates, the activation of these receptors suppresses synaptic vesicle release by reducing the amount of calcium that enters the axon terminal as a result of an action potential (Wachowiak and Cohen 1999; Wachowiak et al. 2005). The component of presynaptic inhibition controlled by GABA could result from spillover within a glomerulus from GABAergic periglomerular neurons activated either directly by the olfactory receptor neurons or indirectly by activity in interglomerular superficial short axon cells (Aungst et al. 2003) or the mitral/tufted cells (Murphy et al. 2005).
We studied the effects of blocking presynaptic inhibition in vivo to determine its role in shaping the response to odor stimulation. The spatio-temporal structure of the response to odorants in vivo will be much more complex than the input resulting from electric shocks to the olfactory nerve layer in a slice preparation. In addition, the milieu of the presynaptic terminals might differ substantially in the tonic concentration of neurotransmitters and neuromodulators between in vitro and in vivo preparations. Finally, some of the three-dimensional structure of the olfactory bulb is lost and feedback from higher brain centers is removed in the in vitro preparation.
Here we present evidence that interglomerular center-surround inhibition shapes the odorant-evoked input in vivo through GABAergic presynaptic inhibition at olfactory receptor axon terminals. We used a local drug perfusion protocol to compare the maps of odorant-evoked input to the mouse olfactory bulb under control conditions and after blocking the presynaptic GABAB receptors with the antagonist CGP46381. We found that the GABAB antagonist qualitatively changes the input map in a manner consistent with blockage of interglomerular center-surround inhibition acting presynaptically on the afferent axon terminals.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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). During surgery and recording, animals were anesthetized with pentobarbital sodium. Bone over one dorsal olfactory bulb was removed, but the dura matter was left intact. The exposed part of the brain was kept immersed in Ringer solution and covered with a coverslip. CGP46381 was bath-applied by replacing this solution. In control measurements, the solution was replaced at the intervals used for the drug protocol. Before addition, the replacement solution was heated to 34°C to approximate the temperature of the exposed portion of the olfactory bulb. A double tracheotomy was performed to allow controlled flow of air through the nasal cavity; the animals breathed freely through the lower canula. All procedures were approved by the Yale University and the Marine Biological Laboratory animal care committees. Olfactometer
To minimize the possibility of any mechanical response to the introduction of odorant into the airflow, we made several modifications, shown in Fig. 1, to the odorant delivery and respiration apparatus described earlier (Lam et al. 2000). The new olfactometer (Fig. 1A) was connected so that the saturated odorant vapor, when introduced into the airflow, replaced the equivalent volume of diluent air. This insured that the rate, humidity, and direction of airflow over the nares stayed constant throughout a measurement. The artificial respiration system (Fig. 1B) was connected so that the open end of the valve that performed artificial sniffing was taking air in through a partially open tap, which was adjusted so that its resistance to air flow matches the resistance of the nasal passages. This allowed a more precise metering of the flow rate through the nose. An electronic pressure sensor (Honeywell ASCX01DN) connected at the output of the rostrally directed tracheal canula enabled early detection of tracheal collapse.
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Optical recording
The dorsal olfactory bulb was imaged through Wild 10 x 0.4 NA or 7 x 0.2 NA objectives mounted onto an antique Leitz Ortholux II upright microscope; the actual magnifications of the two lenses were x15 and x10, respectively. Excitation light from a 150-W xenon arc lamp was passed through a 480/50-nm band-pass filter and reflected by a 515-nm dichroic mirror. The fluorescence above 530 nm was recorded with a NeuroCCD-SM or NeuroCCD-SM256 camera using NeuroPlex software (RedShirtImaging, Fairfield, CT).
Data analysis
Activated glomeruli were identified manually in each preparation based on the spatial pattern of stimulus-evoked activation (between 17 and 42 per preparation). Small shifts in the position of the preparation relative to the camera were corrected for in software by comparing the spatial patterns of the resting fluorescence intensity at every recording.
The blue trace in the top section of Fig. 2A shows the time-course of the calcium green-1 fluorescence response from a single glomerulus to a 2-s presentation of the odorant 2-hexanone at 1% of saturation. The black trace shows the same data temporally filtered with a low-pass Gaussian filter (f0 = 1.2 Hz); the two black bars below the trace indicate the frames used for the subtractions to make the maps of activity shown in Figs. 2B and Fig. 4. The prestimulus period of every recording was fit with an exponential decay curve; the extension of this fit into the stimulus period was subtracted from the signal to give the signal amplitude (Fig. 2A). In the data presented here, only the first 2 s after stimulus onset were used in quantifying the response (Fig. 2A, gray area) to minimize contributions from any intrinsic signal. Similar results were obtained if we used the peak or the values at 0.5, 1, 1.5, or 2 s after stimulus onset (data not shown).
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We used the following measure to quantify the effect of blocking presynaptic inhibition on the relationship between the center and the surround signals
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F/F. The inability to correct for the background fluorescence will tend to reduce the slope seen in Fig. 6B. In addition, blurring of the signals from scattering or out-of-focus light would also tend to reduce the slope seen in Fig. 6B. CGP46381 was applied to 14 of the 24 preparations. A partially overlapping group of 14 preparations had a control period of sufficient duration for the analysis shown in Fig. 3A. Five of the experiments with the drug protocol were rejected for further analysis because the measured effect of the drug was below the 21% threshold of significance. The concentrations of CGP46381 in the Ringer solution were 1 (n = 8) and 0.1 mM (n = 1). The effects of CGP46381 were not reversible during the 1-h wash-out periods we used.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Wachowiak and Cohen 2001), to monitor the level of presynaptic activity in the receptor nerve terminals in the olfactory bulb glomeruli. Figure 2B shows a grayscale map of odorant-induced activity; individual glomeruli are readily distinguishable. Response stability
To quantify the stability of our preparations, we determined the signal amplitudes (Fig. 2A) of 367 glomeruli recorded from 14 animals through periods of undisturbed repeated measurements (Fig. 2A, control period). The results of these control measurements are shown in Fig. 3A. Figure 3B shows a histogram (points) of the relative change of amplitudes of 367 glomeruli between two measurements (each consisting of 4 averaged trials) made 20 min apart under unchanging conditions. This distribution agrees well with a lognormal distribution function shown in red. Consistent with the result shown in Fig. 3A, the center of the distribution lies slightly below 1, indicating a slow decline of the average amplitude over time, which could be caused by a combination of dye bleaching, photodynamic damage, and run-down of the preparation. From the fitted distribution function, we conclude that amplitudes of <5% of all glomeruli are expected to fluctuate upward by chance by >21% (the region to the right of the vertical line; Fig. 3B) over the course of the drug protocol. Because some sources of noise are expected to have effects that are correlated between glomeruli (e.g., fluctuations in odorant delivery will tend to affect all glomeruli in a similar manner; Fig. 6 in Wachowiak and Cohen 2001), we used this distribution as a conservative way to estimate the significance of any drug-induced change in the amplitude of an ensemble of glomeruli.
Effect of GABAB antagonists on signal amplitude
The brain-penetrant, competitive GABAB antagonist CGP46381 caused a long-lasting increase in the average amplitude of the presynaptic calcium signal when bath-applied at millimolar concentration (Fig. 3C). This effect was dependent on the age of the animal: it was usually present in juvenile mice (14–29 days old) and usually absent in mature mice (>30 days old). We only used the data recorded from animals younger than 30 days. Furthermore, we did not analyze the experiments where the increase of signal amplitude over the course of the protocol was <21% above the baseline (the last set of 4 trials before the application of the drug) amplitude; the probability of the baseline signal fluctuating past this cut-off as a result of noise was measured to be <5% as described above. Nine experiments passed these criteria.
Effect of GABAB antagonists on the input map
Odorant-evoked input maps are altered when GABAB receptors are blocked. Figure 4 shows examples of the alteration from two different preparations. The color scale has been adjusted between the baseline and drug-perfused recordings to compensate for the increase in calcium signal amplitude after the addition of CGP46381 in the glomeruli with the largest signals. In both preparations, there is a more prominent activation of many weakly activated areas after presynaptic inhibition is blocked, as would be expected if strongly activated glomeruli normally suppressed the weakly activated ones. In the following, we present two different measurements quantifying this observation.
REDUCTION OF MAP CONTRAST. First, in Fig. 5, we plot cumulative distributions of normalized glomerular signal amplitudes. Figure 5B shows that there is a shift to the right after perfusion with CGP46381 (solid line) compared with the baseline distribution (dashed line; a total of 251 glomeruli in 9 animals; P < 0.001, Kolmogorov-Smirnov test). This is a manifestation of the reduction of input map contrast. Figure 5A shows that no such shift occurred when we compared two measurements from the control dataset where no drug was applied (a total of 367 glomeruli in 14 animals; P > 0.7).
CENTER-SURROUND ANALYSIS.
Next we measured the effect of the GABAB antagonist on the glomerular signal and the surround signal (Fig. 2B) as a function of the relative activation of the glomerulus and the surround. In Fig. 6B, we plot the ratio of relative change of the amplitudes of glomeruli and their surrounds against the ratio of the amplitude of a glomerulus and its surround before the drug was applied. When presented in this manner, the glomeruli will be distributed along a horizontal line at y = 1 if their amplitudes did not change but also if all the amplitudes were scaled by a constant. The noise in the measurement is shown by the analogous plot (Fig. 6A) from a control data set, where we only replaced the vehicle. Figure 6B shows that the GABAB antagonist produced a marked correlation between the two quantities that would not be present if the drug had a proportional effect on all glomeruli. To quantify the level of correlation, we fit the function y = 1 + a log(x/b) to these data (red lines in the figure): the slope of the best fit is a = 0.53 ± 0.04 (P < 0.0001) compared with a = 0.07 ± 0.03 for the control data (optimal value ± SD). These results were not significantly affected by excluding the data from glomeruli whose identity was questionable (e.g., the diffuse spot in the bottom right of Fig. 2B). Errors in the calculation of F/F resulting from the fact that we did not subtract the background fluorescence (before staining) and blurring of the signals from scattering or out-of-focus light would both tend to reduce the slope seen in Fig. 6B. The slope of the line in Fig. 6B indicates that for glomerular signals that are eight times larger than the average surround, CGP46381 caused an increase in the surround that was approximately twice as large as the increase in the glomerulus. As another control, after perfusion of a D2 receptor agonist we observed an overall reduction in signal amplitude that was not accompanied by a significant correlation when the data were plotted as in Fig. 6 (data not shown). We conclude that strongly activated glomeruli are relatively less suppressed by GABAergic presynaptic inhibition than their surround.
One concern was the possibility that the correlation shown in Fig. 6B, as well as the reduction of contrast in Fig. 4 and the shift in the cumulative distribution in Fig. 5B, are a consequence of a simple nonlinearity in the effect of the drug on the population calcium signal. For example, if strongly activated glomeruli are operating near the saturation of the calcium signal, it is conceivable that the drug could simply have a greater effect on weakly activated glomeruli, thereby changing quality of the input map but not actually resulting from lateral inhibition. To test for this possibility, in Fig. 7 we plotted the relative change of amplitude of a glomerulus caused by perfusion of CGP46381 against its normalized baseline amplitude, without regard for the surround. This distribution does, indeed, show that weakly activated glomeruli are relatively more affected by the GABAB antagonist, an effect that could be caused either by saturation or by blocking lateral inhibition. To distinguish the two possibilities, we compared the surrounds of only modestly activated glomeruli that show similar baseline activation but undergo a different change after drug perfusion. The noise in the data necessitates the comparison of several glomeruli, so we divided all the glomeruli near the middle of the observed dynamic range into two groups along the median (outlined in red and blue in Fig. 7). This band was chosen with the following rationale: strongly activated glomeruli were not used because any saturation effects would show here first; weakly activated glomeruli were not used because noise dominates in this region; the band was extended from a normalized amplitude of 0.5 to lower values until enough glomeruli were included to reach a conclusion that was statistically significant. The glomeruli so selected that were more affected by the GABAB antagonist did, in fact, have more strongly activated surrounds before the drug application: the ratio of amplitudes of a glomerulus and its surround is 1.61 ± 0.12 for the more affected (red box) compared with 1.97 ± 0.16 for the less affected (blue box) set of glomeruli (mean ± SE; P < 0.05, t-test). The glomeruli from the excluded regions show a similar trend, making this P value a conservative estimate. Therefore the alteration of the input map cannot simply be explained by nonlinearity alone.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Ennis et al. 2001; Duchamp-Viret et al. 2002; Nickell et al. 1994; Wachowiak and Cohen 1999; Wachowiak et al. 2005). A question left unanswered by these studies was what role, if any, do these presynaptic modulatory mechanisms play in shaping the input elicited by odorants in vivo. The results we present here provide the first evidence that presynaptic inhibition modifies the receptor neuron input evoked in vivo by odorant presentation to the nose.
The roles suggested for presynaptic inhibition of release from olfactory afferents were thought to be local to a glomerulus: the relative suppression of weak signals through tonic activation, the relative enhancement of sensitivity to novel odorants (Aroniadou-Anderjaska et al. 2000), and the increase of the dynamic range of glomerular response to different concentrations of an odorant (Wachowiak et al. 2002). More recent evidence points to the possibility of disynaptic inhibitory communication between glomeruli through superficial short axon cells with mean axon lengths of 300–400 µm, four to five glomeruli (Aungst et al. 2003), as well as dendro-dendritic activation of GABAergic periglomerular interneurons by mitral/tufted neurons (Murphy et al. 2005), where the release of GABA inhibits further glutamate release from afferent terminals. In addition, the mitral/tufted neurons form a widespread network through the classical dendro-dendritic synapses with granule cells (Rall et al. 1966). Because of the relatively long space constant of the mitral cell apical dendrite (Djurisic et al. 2004), membrane potential changes can reliably spread from the soma back to the glomerular tuft. Thus there are a number of candidate pathways for inhibiting afferent input as a result of activity that is not local to a glomerulus.
Our results indicate that one component of the modification of the presynaptic calcium signal is a relative suppression of the surround of strongly activated glomeruli, which increases the contrast of the input map. The apparent absence of axo-axonic synapses in glomeruli (Bonino et al. 1999; Shepherd and Greer 1998) suggests that this effect is a result of spillover within a glomerulus of GABA released from periglomerular neurons that are activated by one or more interglomerular circuits. Thus the presynaptic terminal responds to the average level of GABA within a glomerulus at a time scale of spillover, an order of magnitude slower than direct synaptic communication
Several pieces of evidence suggest that the map change we observed is not an artifact of nonlinearity of the effect of the GABAB antagonist on the amplitude of the calcium signal.
First, if we select a subset of glomeruli on the basis of their modest level of activation to minimize the possibility of encountering saturation, and without regard for their location in the map, the glomeruli that are nearer strongly activated regions behave differently under the antagonist than the ones that are further away (Fig. 7). Such an effect cannot be produced by a local, intraglomerular circuit. For instance, while tonic activation of GABAB receptors is likely to introduce a nonlinearity into the response to an exogenous GABAB receptor antagonist, the manifestation of this kind of nonlinearity will be the same regardless of how distant a glomerulus is from a strongly activated one. In addition, the proximity effect cannot be artificially produced by cross-talk between glomeruli that mixes their signals, such as the scattering of light and the limited spatial resolution of the measurement apparatus, as any indiscriminate mixing will dilute the observed difference.
Second, recent reports point to a nearly linear dependence of the probability of release from olfactory receptor neuron terminals on the extracellular calcium concentration (Murphy et al. 2004; Wachowiak et al. 2005) and to a nearly linear dependence of release failure probability at a central synapse on the calcium signal reported by an indicator of affinity similar to the one we used (Koester and Johnston 2005). These results do not favor a large nonlinearity between the response of our indicator and neurotransmitter release. Because network-mediated center-surround inhibition is expected to create results like those shown in Figs. 4–6, we conclude that interglomerular communication is the most likely explanation for the map modification. The modification of the presynaptic map is not the only effect of CGP46381; the amplitude of the calcium signal is increased (Fig. 3C) implying that presynaptic inhibition has other important functions in addition to altering the map.
From recent experiments using synaptopHluorin loaded presynaptic terminals, McGann et al. (2005a) concluded that "inhibitory connections between glomeruli mediated ... lateral inhibition between olfactory sensory neuron inputs in slices but did not do so in response to odorant stimulation in vivo". Surprisingly, some data that they present (McGann et al. 2005b; Fig. 8A of McGann, et al. 2005a) show clear examples of relatively increased responses by weakly responding glomeruli after blocking presynaptic inhibition.
The relative contribution of the different interglomerular circuits to the modification of the presynaptic input map are unknown. In the future this question might be addressed by recording the maps of the activity of specific juxtaglomerular neuron types through the use of genetically targeted indicators of activity in concert with drugs that selectively inactivate the particular circuits. Similar measurements from the output neurons (mitral/tufted cells) would provide a measure of the sum of all the interglomerular effects generated in the olfactory bulb.
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ini thanks P. Sphicas, J. Friedman, and G. Bauer for guidance and support. E. K. Kosmidis thanks M. Dounis for enabeling participation in these experiments. |
FOOTNOTES |
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Address for reprint requests and other correspondence: D. Vuini, The Salk Inst., 10010 North Torrey Pines Rd., La Jolla, CA 92037-1099 (E-mail: dejan{at}salk.edu)
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Aungst JL, Heyward PM, Puche AC, Karnup SV, Hayar A, Szabo G, and Shipley MT. Centre-surround inhibition among olfactory bulb glomeruli. Nature 426: 623–629, 2003.[CrossRef][Medline]
Bonino M, Cantino D, and Sassoè-Pognetto M. Cellular and subcellular localization of 
-aminobutyric acidB receptors in the rat olfactory bulb. Neurosci Lett 274: 195–198, 1999.[CrossRef][ISI][Medline]
Djurisic M, Antic S, Chen WR, and Zecevic D. Voltage imaging from dendrites of mitral cells: EPSP attenuation and spike trigger zones. J Neurosci 28: 6703–6714, 2004.
Duchamp-Viret P, Delaleu JC, and Duchamp A. GABAB-mediated action in the frog olfactory bulb makes odor responses more salient. Neuroscience 97: 771–777, 2002.
Ennis M, Zhou FM, Ciombor KJ, Aroniadou-Anderjaska V, Hayar A, Borrelli E, Zimmer LA, Margolis F, and Shipley MT. Dopamine D2 Receptor-mediated presynaptic inhibition of olfactory nerve terminals. J Neurophysiol 86: 2986–2997, 2001.
Friedrich RW and Korsching SI. Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging. Neuron 18: 737–752, 1997.[CrossRef][ISI][Medline]
Kay LM and Laurent G. Odor- and context-dependent modulation of mitral cell activity in behaving rats. Nat Neurosci 11: 1003–1009, 1999.
Koester HJ and Johnston D. Target cell-dependent normalization of transmitter release at neocortical synapses. Science 308: 863–866, 2005.
Lam YW, Cohen LB, Wachowiak M, and Zochowski MR. Odors elicit three different oscillations in the turtle olfactory bulb. J Neurosci 20: 749–762, 2000.
Laurent G. A systems perspective on early olfactory coding. Science 286: 723–728, 1999.
McGann JP, Pirez N, Gainey MA, Muratore C, Elias AS, and Wachowiak M. Odorant representations are modulated by intraglomerular but not interglomerular presynaptic inhibition of olfactory sensory neurons. Neuron 48: 1039–1053, 2005a.[CrossRef][ISI][Medline]
McGann JP, Pirez N, Muratore C, Elias AS, Gainey MA, and Wachowiak M. Modulation of odorant representations by feedback versus lateral presynaptic inhibition of receptor neuron input to the olfactory bulb. Soc Neurosci Abstr 476.4. 2005b.
Meister M and Bonhoeffer T. Tuning and topography in an odor map on the rat olfactory bulb. J Neurosci 21: 1351–1360, 2001.
Murphy GJ, Darcy DP, and Isaacson JS. Intraglomerular inhibition: signaling mechanisms of an olfactory microcircuit. Nat Neurosci 8: 354–364, 2005.[CrossRef][ISI][Medline]
Murphy GJ, Glickfeld LL, Balsen Z, and Isaacson JS. Sensory neuron signaling to the brain: properties of transmitter release from olfactory nerve terminals. J Neurosci 24: 3023–3030, 2004.
Nickell WT, Behbehani MM, and Shipley MT. Evidence for GABAB-mediated inhibition of transmission from the olfactory nerve to mitral cells in the rat olfactory bulb. Brain Res Bull 35: 119–123, 1994.[CrossRef][ISI][Medline]
Perez-Orive J, Mazor O, Turner GC, Cassenaer S, Wilson RI, and Laurent G. Oscillations and sparsening of odor representations in the mushroom body. Science 297: 359–365, 2002.
Rall W, Shepherd GM, Reese TS, and Brightman MW. Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. Exp Neurol 14: 44–56, 1966.[CrossRef][ISI][Medline]
Ressler KJ, Sullivan SL, and Buck LB. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79: 1245–1255, 1994.[CrossRef][ISI][Medline]
Rubin BD and Katz LC. Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron 23: 499–511, 1999.[CrossRef][ISI][Medline]
Shepherd GM and Greer CA. Olfactory bulb. In: The Synaptic Organization of the Brain (4th ed.), edited by Shepherd GM. New York: Oxford, 1998, p. 159–203.
Treloar HB, Feinstein P, Mombaerts P, and Greer CA. Specificity of glomerular targeting by olfactory sensory axons. J Neurosci 22: 2469–2477, 2002.
Wachowiak M and Cohen LB. Presynaptic inhibition of primary olfactory afferents mediated by different mechanisms in lobster and turtle. J Neurosci 19: 8808–8817, 1999.
Wachowiak M and Cohen LB. Representation of odorants by receptor neuron input to the mouse olfactory bulb. Neuron 32: 723–735, 2001.[CrossRef][ISI][Medline]
Wachowiak M, Cohen LB, and Ache BW. Presynpatic inhibition of olfactory receptor neurons in crustaceans. Microsc Res Tech 58: 365–375, 2002.[CrossRef][ISI][Medline]
Wachowiak M, McGann JP, Heyward PM, Shao Z, Puche AC, and Shipley MT. Inhibition of olfactory receptor neuron input to olfactory bulb glomeruli mediated by suppression of presynaptic calcium influx. J Neurophysiol 94: 2700–2712, 2005.
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N as an approximation of the SD of a normally distributed quantity to aid in determining the quality of the fit. Solid line is a fit to this data of a lognormal distribution function. Vertical line marks our cut-off for significant drug-induced change: the integral of the fit distribution over the region marked by the arrow is <5%. C: in most preparations, the GABAB antagonist CGP46831 caused a long-lasting increase in the average amplitude of the calcium signal. Each point is the amplitude of glomerular response averaged over all glomeruli in 1 preparation in one trial, divided by the average of 4 responses recorded just before drug perfusion (baseline). Different preparations are shown in different colors. The 9 preparations used in 
