The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Veronica Egger - One of the best experts on this subject based on the ideXlab platform.
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long term plasticity at the mitral and Tufted Cell to granule Cell synapse of the olfactory bulb investigated with a custom multielectrode in acute brain slice preparations
Methods of Molecular Biology, 2018Co-Authors: Michael Lukas, Knut Holthoff, Veronica EggerAbstract:Single extraCellular stimulation electrodes are a widespread means to locally activate synaptic inputs in acute brain slices. Here we describe the fabrication and application of a multielectrode stimulator that was developed for conditions under which independent stimulation of several nearby sites is desirable. For the construction of the multielectrode we have developed a method by which electrode wires can be spaced at minimal distances of 100 μm. This configuration increases the efficiency of stimulation paradigms, such as the comparison of proximal induced and control inputs for studies of synaptic plasticity.In our case the multielectrode was used for acute olfactory bulb slices to independently excite individual nearby glomeruli; the technique allowed us to demonstrate homosynaptic bidirectional long-term plasticity at the mitral/Tufted Cell to granule Cell synapse. We also describe the determinants for successful recordings of long-term plasticity at this synapse, with mechanical and electrophysiological recording stability being tantamount. Finally, we briefly discuss data analysis procedures.
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sniff like patterned input results in long term plasticity at the rat olfactory bulb mitral and Tufted Cell to granule Cell synapse
Neural Plasticity, 2016Co-Authors: Mahua Chatterjee, Michael Lukas, Veronica Egger, Fernando Perez De Los Cobos Pallares, Alex LoebelAbstract:During odor sensing the activity of principal neurons of the mammalian olfactory bulb, the mitral and Tufted Cells (MTCs), occurs in repetitive bursts that are synchronized to respiration, reminiscent of hippocampal theta-gamma coupling. Axonless granule Cells (GCs) mediate self- and lateral inhibitory interactions between the excitatory MTCs via reciprocal dendrodendritic synapses. We have explored long-term plasticity at this synapse by using a theta burst stimulation (TBS) protocol and variations thereof. GCs were excited via glomerular stimulation in acute brain slices. We find that TBS induces exclusively long-term depression in the majority of experiments, whereas single bursts ("single-sniff paradigm") can elicit both long-term potentiation and depression. Statistical analysis predicts that the mechanism underlying this bidirectional plasticity involves the proportional addition or removal of presynaptic release sites. Gamma stimulation with the same number of APs as in TBS was less efficient in inducing plasticity. Both TBS- and "single-sniff paradigm"-induced plasticity depend on NMDA receptor activation. Since the onset of plasticity is very rapid and requires little extra activity, we propose that these forms of plasticity might play a role already during an ongoing search for odor sources. Our results imply that components of both short-term and long-term olfactory memory may be encoded at this synapse.
Matt Wachowiak - One of the best experts on this subject based on the ideXlab platform.
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differential impacts of repeated sampling on odor representations by genetically defined mitral and Tufted Cell subpopulations in the mouse olfactory bulb
The Journal of Neuroscience, 2020Co-Authors: Thomas P. Eiting, Matt WachowiakAbstract:Sniffing, the active control of breathing beyond passive respiration, is used by mammals to modulate olfactory sampling. Sniffing allows animals to make odor-guided decisions within ∼200 ms, but animals routinely engage in bouts of high-frequency sniffing spanning several seconds; the impact of such repeated odorant sampling on odor representations remains unclear. We investigated this question in the mouse olfactory bulb (OB), where mitral and Tufted Cells (MTCs) form parallel output streams of odor information processing. To test the impact of repeated odorant sampling on MTC responses, we used two-photon imaging in anesthetized male and female mice to record activation of MTCs while precisely varying inhalation frequency. A combination of genetic targeting and viral expression of GCaMP6 reporters allowed us to access mitral Cell (MC) and superficial Tufted Cell (sTC) subpopulations separately. We found that repeated odorant sampling differentially affected responses in MCs and sTCs, with MCs showing more diversity than sTCs over the same time period. Impacts of repeated sampling among MCs included both increases and decreases in excitation, as well as changes in response polarity. Response patterns across simultaneously-imaged MCs reformatted over time, with representations of different odorants becoming more distinct. Individual MCs responded differentially to changes in inhalation frequency, whereas sTC responses were more uniform over time and across frequency. Our results support the idea that MCs and TCs comprise functionally distinct pathways for odor information processing, and suggest that the reformatting of MC odor representations by high-frequency sniffing may serve to enhance the discrimination of similar odors.SIGNIFICANCE STATEMENT Repeated sampling of odorants during high-frequency respiration (sniffing) is a hallmark of active odorant sampling by mammals; however, the adaptive function of this behavior remains unclear. We found distinct effects of repeated sampling on odor representations carried by the two main output channels from the mouse olfactory bulb (OB), mitral and Tufted Cells (MTCs). Mitral Cells (MCs) showed more diverse changes in response patterns over time as compared with Tufted Cells (TCs), leading to odorant representations that were more distinct after repeated sampling. These results support the idea that MTCs contribute different aspects to encoding odor information, and they indicate that MCs (but not TCs) may play a primary role in the modulation of olfactory processing by sampling behavior.
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Differential impacts of repeated sampling on odor representations by genetically-defined mitral and Tufted Cell subpopulations in the mouse olfactory bulb
2020Co-Authors: Thomas P. Eiting, Matt WachowiakAbstract:Abstract Sniffing—the active control of breathing beyond passive respiration—is used by mammals to modulate olfactory sampling. Sniffing allows animals to make odor-guided decisions within ~200 ms, but animals routinely engage in bouts of high-frequency sniffing spanning several seconds; the impact of such repeated odorant sampling on odor representations remains unclear. We investigated this question in the mouse olfactory bulb, where mitral and Tufted Cells (MTCs) form parallel output streams of odor information processing. To test the impact of repeated odorant sampling on MTC responses, we used two-photon imaging in anesthetized male and female mice to record activation of MTCs while precisely varying inhalation frequency. A combination of genetic targeting and viral expression of GCaMP6 reporters allowed us to access mitral (MC) and superficial Tufted Cell (sTC) subpopulations separately. We found that repeated odorant sampling differentially affected responses in MCs and sTCs, with MCs showing more diversity than sTCs over the same time period. Impacts of repeated sampling among MCs included both increases and decreases in excitation, as well as changes in response polarity. Response patterns across ensembles of simultaneously-imaged MCs reformatted over time, with representations of different odorants becoming more distinct. MCs also responded differentially to changes in inhalation frequency, whereas sTC responses were more uniform over time and across frequency. Our results support the idea that MCs and TCs comprise functionally distinct pathways for odor information processing, and suggest that the reformatting of MC odor representations by high-frequency sniffing may serve to enhance the discrimination of similar odors.
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inhalation frequency controls reformatting of mitral Tufted Cell odor representations in the olfactory bulb
The Journal of Neuroscience, 2018Co-Authors: Marta Diazquesada, Michael N Economo, Kyle R Hansen, Isaac A Youngstrom, Yusuke Tsuno, Matt WachowiakAbstract:In mammals, olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and Tufted (MT) Cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT Cell odor responses, we obtained whole-Cell recordings from MT Cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across Cells. We characterized frequency effects on MT Cell responses during inhalation of air and odorants using inhalation pulses and also “playback” of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well predicted across frequency from linear convolution of 1 Hz responses; and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT Cells, with some Cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT Cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT Cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling. SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on inhalation, which increases in frequency during active sampling of olfactory stimuli. We asked how inhalation frequency can shape the neural coding of odor information by recording from projection neurons of the olfactory bulb while artificially varying odor sampling frequency in the anesthetized mouse. We found that sampling an odor at higher frequencies led to diverse changes in net responsiveness, as measured by action potential output, that were not predicted from low-frequency responses. These changes led to a reorganization of the pattern of neural activity evoked by a given odorant that occurred preferentially during sustained, high-frequency inhalation. These results point to a novel mechanism for modulating early sensory representations solely as a function of sampling behavior.
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inhalation frequency controls reformatting of mitral Tufted Cell odor representations in the olfactory bulb
bioRxiv, 2018Co-Authors: Marta Diazquesada, Michael N Economo, Kyle R Hansen, Isaac A Youngstrom, Yusuke Tsuno, Matt WachowiakAbstract:In mammals olfactory sensation depends on inhalation, which controls activation of sensory neurons and temporal patterning of central activity. Odor representations by mitral and Tufted (MT) Cells, the main output from the olfactory bulb (OB), reflect sensory input as well as excitation and inhibition from OB circuits, which may change as sniff frequency increases. To test the impact of sampling frequency on MT Cell odor responses, we obtained whole-Cell recordings from MT Cells in anesthetized male and female mice while varying inhalation frequency via tracheotomy, allowing comparison of inhalation-linked responses across Cells. We characterized frequency effects on MT Cell responses during inhalation of air and odorants using inhalation pulses and also playback of sniffing recorded from awake mice. Inhalation-linked changes in membrane potential were well-predicted across frequency from linear convolution of 1 Hz responses and, as frequency increased, near-identical temporal responses could emerge from depolarizing, hyperpolarizing or multiphasic MT responses. However, net excitation was not well predicted from 1 Hz responses and varied substantially across MT Cells, with some Cells increasing and others decreasing in spike rate. As a result, sustained odorant sampling at higher frequencies led to increasing decorrelation of the MT Cell population response pattern over time. Bulk activation of sensory inputs by optogenetic stimulation affected MT Cells more uniformly across frequency, suggesting that frequency-dependent decorrelation emerges from odor-specific patterns of activity in the OB network. These results suggest that sampling behavior alone can reformat early sensory representations, possibly to optimize sensory perception during repeated sampling.
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control of mitral Tufted Cell output by selective inhibition among olfactory bulb glomeruli
Neuron, 2016Co-Authors: Michael N Economo, Kyle R Hansen, Matt WachowiakAbstract:Inhibition is fundamental to information processing by neural circuits. In the olfactory bulb (OB), glomeruli are the functional units for odor information coding, but inhibition among glomeruli is poorly characterized. We used two-photon calcium imaging in anesthetized and awake mice to visualize both odorant-evoked excitation and suppression in OB output neurons (mitral and Tufted, MT Cells). MT Cell response polarity mapped uniformly to discrete OB glomeruli, allowing us to analyze how inhibition shapes OB output relative to the glomerular map. Odorants elicited unique patterns of suppression in only a subset of glomeruli in which such suppression could be detected, and excited and suppressed glomeruli were spatially intermingled. Binary mixture experiments revealed that interglomerular inhibition could suppress excitatory mitral Cell responses to odorants. These results reveal that inhibitory OB circuits nonlinearly transform odor representations and support a model of selective and nonrandom inhibition among glomerular ensembles.
Andreas T Schaefer - One of the best experts on this subject based on the ideXlab platform.
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sniffing fast paradoxical effects on odor concentration discrimination at the levels of olfactory bulb output and behavior
eNeuro, 2018Co-Authors: Mihaly Kollo, Andreas T Schaefer, Rebecca JordanAbstract:Abstract In awake mice, sniffing behavior is subject to complex contextual modulation. It has been hypothesized that variance in inhalation dynamics alters odor concentration profiles in the naris despite a constant environmental concentration. Using whole-Cell recordings in the olfactory bulb of awake mice, we directly demonstrate that rapid sniffing mimics the effect of odor concentration increase at the level of both mitral and Tufted Cell (MTC) firing rate responses and temporal responses. Paradoxically, we find that mice are capable of discriminating fine concentration differences within short timescales despite highly variable sniffing behavior. One way that the olfactory system could differentiate between a change in sniffing and a change in concentration would be to receive information about the inhalation parameters in parallel with information about the odor. We find that the sniff-driven activity of MTCs without odor input is informative of the kind of inhalation that just occurred, allowing rapid detection of a change in inhalation. Thus, a possible reason for sniff modulation of the early olfactory system may be to directly inform downstream centers of nasal flow dynamics, so that an inference can be made about environmental concentration independent of sniff variance.
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two distinct channels of olfactory bulb output
Neuron, 2012Co-Authors: Izumi Fukunaga, Manuel Berning, Mihaly Kollo, Anja Schmaltz, Andreas T SchaeferAbstract:Rhythmic neural activity is a hallmark of brain function, used ubiquitously to structure neural information. In mammalian olfaction, repetitive sniffing sets the principal rhythm but little is known about its role in sensory coding. Here, we show that mitral and Tufted Cells, the two main classes of olfactory bulb projection neurons, tightly lock to this rhythm, but to opposing phases of the sniff cycle. This phase shift is established by local inhibition that selectively delays mitral Cell activity. Furthermore, while Tufted Cell phase is unperturbed in response to purely excitatory odorants, mitral Cell phase is advanced in a graded, stimulus-dependent manner. Thus, phase separation by inhibition forms the basis for two distinct channels of olfactory processing.
Regina M Sullivan - One of the best experts on this subject based on the ideXlab platform.
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the d2 antagonist spiperone mimics the effects of olfactory deprivation on mitral Tufted Cell odor response patterns
The Journal of Neuroscience, 1995Co-Authors: Donald A Wilson, Regina M SullivanAbstract:Wistar rats had a single nare occluded on postnatal day 30, depriving the ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either 1–2 months (short-term) or 12 months (long-term). As previously reported, deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate limiting enzyme for dopamine synthesis) in the glomerular layer of the ipsilateral olfactory bulb. The nare was then reopened and odor response patterns of mitral/Tufted Cells were examined. The proportion of mitral/Tufted Cell single-units responding to a single odor was enhanced by deprivation. Furthermore, the proportion of mitral/Tufted Cells responding to more than one odor was increased by deprivation, suggesting a decrease in discrimination. Finally, in undeprived bulbs, the dopamine D2 receptor antagonist spiperone mimicked the effects of deprivation on mitral/Tufted Cell odor response patterns. The results are interpreted as an activity- dependent dopamine modulation of lateral and feedback inhibition in the olfactory bulb, and are compared with similar events in the dark- adapted retina.
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the d2 antagonist spiperone mimics the effects deprivation on mitral Tufted Cell odor response of olfactory patterns
1995Co-Authors: Donald A Wilson, Regina M SullivanAbstract:Wistar rats had a single nare occluded on postnatal day 30, depriving the ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either l-2 months (short-term) or 12 months (long-term). As previously reported, deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate limiting enzyme for dopamine synthesis) in the glomerular layer of the ipsilateral olfactory bulb. The nare was then reopened and odor response patterns of mitral/Tufted Cells were examined. The proportion of mitral/ Tufted Cell single-units responding to a single odor was enhanced by deprivation. Furthermore, the proportion of mi
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blockade of mitral Tufted Cell habituation to odors by association with reward a preliminary note
Brain Research, 1992Co-Authors: Donald A Wilson, Regina M SullivanAbstract:Association of odor and reward during the early postnatal period modifies rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bulb output neurons, mitral/Tufted Cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairings prevent mitral/Tufted Cell habituation to the odor that normally occurs to repeated odor-only stimulation. It is hypothesized that the maintenance of olfactory bulb responses to conditioned odors during training may allow for activation of long-term memory mechanisms.
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olfactory associative conditioning in infant rats with brain stimulation as reward ii norepinephrine mediates a specific component of the bulb response to reward
Behavioral Neuroscience, 1991Co-Authors: Donald A Wilson, Regina M SullivanAbstract:The olfactory bulb receives extensive centrifugal inputs conveying information regarding a variety of internal states such as arousal level, hunger, and sexual receptivity. Responses of the bulb to odors can be modulated by these centrifugal inputs (Cattarelli, 1982; Gray, Freeman, & Skinner, 1986; Pager, 1978; Potter & Chorover, 1976). For example, responses of mitral-Tufted Cells (the primary output neurons of the bulb) to specific odors are dependent on the current level of hunger or behavioral arousal (or both) of the animal (Gervais & Pager, 1979; Scott, 1977). In addition, noradrenergic (NE) centrifugal input to the olfactory bulb may also modulate neural plasticity in that structure, allowing long-term changes in bulb function after associative conditioning or other memorial events (Cornwell-Jones & Bollers, 1983; Gray et al., 1986; Rosser & Keverne, 1985; Sullivan, McGaugh, & Leon, 1991; Sullivan, Wilson, & Leon, 1989). The role of NE in plasticity is not limited to the olfactory bulb because NE has been implicated in synaptic plasticity in other sensory systems (Kasamatsu & Pettigrew, 1979; Bear & Singer, 1986) as well as hippocampal long-term potentiation (Dahl & Sarvey, 1989; Neuman & Harley, 1983). NE is present and functional in the neonatal rat olfactory bulb (McLean & Shipley, 1991; Wilson & Leon, 1988a). Indeed, the role of NE in olfactory bulb plasticity appears to manifest itself at least as soon as the first postnatal week. For example, association of an odor and reinforcer during the preweanling period produces a conditioned behavioral response to that odor that is correlated with specific changes in olfactory bulb neural response patterns. These neural changes include enhanced glomerular layer focal 2-deoxyglucose uptake and modified mitral-Tufted Cell single unit responses to the conditioned odor (Coopersmith & Leon, 1984; Sullivan & Leon, 1986; Wilson, Sullivan, & Leon, 1987). As early as the first postnatal week, blockade of NE activity during pairing of odor and reinforcement prevents both the behavioral and neural changes that normally occur with learning (Sullivan et al., 1989, 1991). Conversely, simultaneous pairing of an odor with an NE β-receptor agonist results in long-term modification of bulb physiology and olfactory behaviors in neonates (Sullivan et al., 1989, 1991). Furthermore, NE agonists combine additively with conventional rewards in early olfactory conditioning (Sullivan et al., 1991). These results suggest that at least one of the loci of odor-reward convergence may occur in the olfactory bulb, which allows associative changes to occur. In support of this hypothesis, we have recently demonstrated that mitral-Tufted Cells respond to medial forebrain bundle-lateral hypothalamic (MFB-LH) stimulation in young rats (Wilson & Sullivan, 1990). Furthermore, pairing an odor with MFB-LH stimulation produces both a conditioned odor preference and modified mitral-Tufted Cell responses to subsequent presentations of that odor (Wilson & Sullivan, 1990). Because NE has been shown to be critically involved in olfactory conditioning, the present study examined the role of NE in associative conditioning using MFB-LH stimulation as reward and the role of NE in mitral-Tufted Cell responses to that reward. We demonstrated that propranolol, a NE antagonist, blocks early olfactory learning with MFB-LH stimulation as reward and that NE may mediate a specific component of mitral-Tufted Cell response to reward in young rats.
Nathan E Schoppa - One of the best experts on this subject based on the ideXlab platform.
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three dimensional synaptic analyses of mitral Cell and external Tufted Cell dendrites in rat olfactory bulb glomeruli
The Journal of Comparative Neurology, 2017Co-Authors: Jennifer N Bourne, Nathan E SchoppaAbstract:Recent studies have suggested that the two excitatory Cell classes of the mammalian olfactory bulb, the mitral Cells (MCs) and Tufted Cells (TCs), differ markedly in physiological responses. For example, TCs are more sensitive and broadly tuned to odors than MCs and also are much more sensitive to stimulation of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological bases for these differences, we performed quantitative ultrastructural analyses of glomeruli in rat olfactory bulb under conditions in which specific Cells were labeled with biocytin and 3,3'-diaminobenzidine. Comparisons were made between MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with large, direct OSN signals and capable of mediating feedforward excitation of MCs. Three-dimensional analysis of labeled apical dendrites under an electron microscope revealed that MCs and eTCs in fact have similar densities of several chemical synapse types, including OSN inputs. OSN synapses also were distributed similarly, favoring a distal localization on both Cells. Analysis of unlabeled putative MC dendrites further revealed gap junctions distributed uniformly along the apical dendrite and, on average, proximally with respect to OSN synapses. Our results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN synapse number or absolute location but rather to a conductance in the MC dendrite that is well positioned to attenuate excitatory signals passing to the Cell soma. Functionally, such a mechanism could allow rapid and dynamic control of OSN-driven action potential firing in MCs through changes in gap junction properties. J. Comp. Neurol. 525:592-609, 2017. © 2016 Wiley Periodicals, Inc.
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Tufted Cell dendrodendritic inhibition in the olfactory bulb is dependent on nmda receptor activity
Journal of Neurophysiology, 2001Co-Authors: Jason M Christie, Nathan E Schoppa, Gary L WestbrookAbstract:Mitral and Tufted Cells constitute the primary output Cells of the olfactory bulb. While Tufted Cells are often considered as "displaced" mitral Cells, their actual role in olfactory bulb processing has been little explored. We examined dendrodendritic inhibition between Tufted Cells and interneurons using whole Cell voltage-clamp recording. Dendrodendritic inhibitory postsynaptic currents (IPSCs) generated by depolarizing voltage steps in Tufted Cells were completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2amino-5-phosphonopentanoic acid (D,L-AP5), whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 2-3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f] quinoxaline-7-sulfonamide (NBQX) had no effect. Tufted Cells in the external plexiform layer (EPL) and in the periglomerular region (PGR) showed similar behavior. These results indicate that NMDA receptor-mediated excitation of interneurons drives inhibition of Tufted Cells at dendrodendritic synapses as it does in mitral Cells. However, the spatial extent of lateral inhibition in Tufted Cells was much more limited than in mitral Cells. We suggest that the sphere of influence of Tufted Cells, while qualitatively similar to mitral Cells, is centered on only one or a few glomeruli.
