Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb

Olfaction in mammals is a dynamic process driven by the inhalation of air through the nasal cavity. Inhalation determines the temporal structure of sensory neuron responses and shapes the neural dynamics underlying central olfactory processing. Inhalation-linked bursts of activity among olfactory bulb (OB) output neurons [mitral/tufted cells (MCs)] are temporally transformed relative to those of sensory neurons. We investigated how OB circuits shape inhalation-driven dynamics in MCs using a modeling approach that was highly constrained by experimental results. First, we constructed models of canonical OB circuits that included mono- and disynaptic feedforward excitation, recurrent inhibition and feedforward inhibition of the MC. We then used experimental data to drive inputs to the models and to tune parameters; inputs were derived from sensory neuron responses during natural odorant sampling (sniffing) in awake rats, and model output was compared with recordings of MC responses to odorants sampled with the same sniff waveforms. This approach allowed us to identify OB circuit features underlying the temporal transformation of sensory inputs into inhalation-linked patterns of MC spike output. We found that realistic input-output transformations can be achieved independently by multiple circuits, including feedforward inhibition with slow onset and decay kinetics and parallel feedforward MC excitation mediated by external tufted cells. We also found that recurrent and feedforward inhibition had differential impacts on MC firing rates and on inhalation-linked response dynamics. These results highlight the importance of investigating neural circuits in a naturalistic context and provide a framework for further explorations of signal processing by OB networks.

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Target Interneuron Preference in Thalamocortical Pathways Determines the Temporal Structure of Cortical Responses

Cerebral Cortex ◽

10.1093/cercor/bhy148 ◽

2018 ◽

Vol 29 (7) ◽

pp. 2815-2831 ◽

Cited By ~ 2

Author(s):

Y Audrey Hay ◽

Jérémie Naudé ◽

Philippe Faure ◽

Bertrand Lambolez

Keyword(s):

Temporal Structure ◽

Sensory Information ◽

Response Duration ◽

Cortical Response ◽

Inhibitory Neurons ◽

Thalamic Nuclei ◽

Response Dynamics ◽

Mean Field Model ◽

Local Circuits ◽

Feedforward Inhibition

Abstract Sensory processing relies on fast detection of changes in environment, as well as integration of contextual cues over time. The mechanisms by which local circuits of the cerebral cortex simultaneously perform these opposite processes remain obscure. Thalamic “specific” nuclei relay sensory information, whereas “nonspecific” nuclei convey information on the environmental and behavioral contexts. We expressed channelrhodopsin in the ventrobasal specific (sensory) or the rhomboid nonspecific (contextual) thalamic nuclei. By selectively activating each thalamic pathway, we found that nonspecific inputs powerfully activate adapting (slow-responding) interneurons but weakly connect fast-spiking interneurons, whereas specific inputs exhibit opposite interneuron preference. Specific inputs thereby induce rapid feedforward inhibition that limits response duration, whereas, in the same cortical area, nonspecific inputs elicit delayed feedforward inhibition that enables lasting recurrent excitation. Using a mean field model, we confirm that cortical response dynamics depends on the type of interneuron targeted by thalamocortical inputs and show that efficient recruitment of adapting interneurons prolongs the cortical response and allows the summation of sensory and contextual inputs. Hence, target choice between slow- and fast-responding inhibitory neurons endows cortical networks with a simple computational solution to perform both sensory detection and integration.

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Long-range GABAergic inhibition modulates spatiotemporal dynamics of the output neurons in the olfactory bulb

10.1101/2020.07.08.194324 ◽

2020 ◽

Cited By ~ 2

Author(s):

Pablo S. Villar ◽

Ruilong Hu ◽

Ricardo C. Araneda

Keyword(s):

Olfactory Bulb ◽

Long Range ◽

Granule Cells ◽

Brain Slices ◽

Gabaergic Neurons ◽

Gabaergic Inhibition ◽

Top Down ◽

Local Interneurons ◽

Output Neurons ◽

Tufted Cells

SUMMARYLocal interneurons of the olfactory bulb (OB) are densely innervated by long-range GABAergic neurons from the basal forebrain (BF), suggesting that this top-down inhibition regulates early processing in the olfactory system. However, how GABAergic inputs modulate the OB output neurons, the mitral/tufted cells, is unknown. Here, in acute brain slices, we show that optogenetic activation of BF GABAergic inputs produced distinct local circuit effects that can influence the activity of mitral/tufted cells in the spatiotemporal domains. Activation of the GABAergic axons produced a fast disinhibition of mitral/tufted cells consistent with a rapid and synchronous release of GABA onto local interneurons in the glomerular and inframitral circuits of the OB, which also reduced the spike precision of mitral/tufted cells in response to simulated stimuli. In addition, BF GABAergic inhibition modulated local oscillations in a layer-specific manner. The intensity of locally evoked θ oscillations was decreased upon activation of top-down inhibition in the glomerular circuit, while evoked γ oscillations were reduced by inhibition of granule cells. Furthermore, BF GABAergic input reduced dendrodendritic inhibition in mitral/tufted cells. Together, these results suggest that long-range GABAergic neurons from the BF are well suited to influence temporal and spatial aspects of processing by OB circuits.

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Complement 3 signaling is necessary for the developmental refinement of olfactory bulb circuitry

10.1101/449454 ◽

2018 ◽

Cited By ~ 1

Author(s):

Katherine S. Lehmann ◽

Alynda Wood ◽

Diana Cummings ◽

Li Bai ◽

Beth Stevens ◽

...

Keyword(s):

Olfactory Bulb ◽

Visual System ◽

Sensory Neuron ◽

Knockout Mice ◽

Olfactory System ◽

Molecular Mechanisms ◽

Complement Receptor ◽

Complement 3 ◽

Complement Receptor 3

AbstractThe olfactory system depends upon organizational maps that are developmentally refined and maintained, however the cellular and molecular mechanisms that underlie these processes are unknown. Studies have shown that microglia and complement molecules are important for the developmental refinement of circuitry within the visual system, thus we asked whether they played a similar role in the olfactory system through the formation of the olfactory bulb (OB) maps, the glomerular and intrabulbar maps. Our findings revealed that microglia in mature animals engulf olfactory sensory neuron (OSN) axons and the synaptic terminals of tufted cells in the glomerular and intrabulbar maps respectively, suggesting microglia could anatomically shape the mature OB circuitry. To determine the mechanisms underlying this axonal pruning activity we used complement 3 (C3) and complement receptor 3 (CR3) knockout mice to investigate if C3 signaling was necessary for precise OB map development. Our results demonstrate that glomerular and intrabulbar map disorganization as typically present in early postnatal mice persists into adulthood when C3 signaling is disrupted. These data clearly establish the C3/CR3 pathway as necessary for the proper developmental refinement of both olfactory maps. We further present the olfactory system as a unique platform to study the role of glia in the development and adult refinement of regenerating circuits.

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Dynamic inhibition of sensory responses mediated by an olfactory corticofugal system

10.1101/2020.03.29.014571 ◽

2020 ◽

Author(s):

Renata Medinaceli Quintela ◽

Jennifer Bauer ◽

Lutz Wallhorn ◽

Daniela Brunert ◽

Markus Rothermel

Keyword(s):

Olfactory Bulb ◽

Sensory Information ◽

Olfactory Cortex ◽

Sensory Response ◽

Anterior Olfactory Nucleus ◽

Output Neurons ◽

Olfactory Processing ◽

Tufted Cells ◽

Sensory Responses ◽

Sensory Evoked

AbstractProcessing of sensory information is substantially modulated by centrifugal projections from higher cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex and its extensive connections to lower and higher brain centers put it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake animals was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed odor responses. This AON mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. These findings suggest that glutamatergic AON projections to the OB suppress early olfactory processing by inhibiting OB output neurons and that the AON can dynamically gate sensory throughput to the cortex.Significance StatementThe anterior olfactory nucleus (AON) as an olfactory information processing area sends extensive projections to lower and higher brain centers but the behavioral consequences of its activation have been scarcely investigated. Using behavioral tests in combination with optogenetic manipulation we show that in contrast to what has been suggested previously, the AON does not seem to form odor percepts but instead suppresses odor responses across odorants and concentrations. Furthermore, this study shows that glutamatergic cortical projections to the olfactory bulb suppress olfactory processing by inhibiting output neurons, pointing to a potential mechanisms by which the olfactory cortex can actively and dynamically gate sensory throughput to higher brain centers.HighlightsAON stimulation suppresses odor responses across odorants and concentrationsAON activation is not perceived as an odorant equivalent cueThe AON dynamically shapes olfactory bulb output on a fast timescaleAON input to the olfactory bulb strongly suppresses mitral/tufted cells firing

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Correction: Mizuguchi et al., Tbr2 Deficiency in Mitral and Tufted Cells Disrupts Excitatory-Inhibitory Balance of Neural Circuitry in the Mouse Olfactory Bulb

Journal of Neuroscience ◽

10.1523/jneurosci.3719-12.2012 ◽

2012 ◽

Vol 32 (39) ◽

pp. 13639-13639 ◽

Cited By ~ 1

Keyword(s):

Olfactory Bulb ◽

Neural Circuitry ◽

Tufted Cells

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Mitral and Tufted Cells Differ in the Decoding Manner of Odor Maps in the Rat Olfactory Bulb

Journal of Neurophysiology ◽

10.1152/jn.01266.2003 ◽

2004 ◽

Vol 91 (6) ◽

pp. 2532-2540 ◽

Cited By ~ 122

Author(s):

Shin Nagayama ◽

Yuji K. Takahashi ◽

Yoshihiro Yoshihara ◽

Kensaku Mori

Keyword(s):

Olfactory Bulb ◽

Spike Activity ◽

Homologous Series ◽

Morphological Difference ◽

Aliphatic Acid ◽

Mitral Cells ◽

Firing Rates ◽

Aliphatic Acids ◽

Projection Pattern ◽

Tufted Cells

Mitral and tufted cells in the mammalian olfactory bulb are principal neurons, each type having distinct projection pattern of their dendrites and axons. The morphological difference suggests that mitral and tufted cells are functionally distinct and may process different aspects of olfactory information. To examine this possibility, we recorded odorant-evoked spike responses from mitral and middle tufted cells in the aliphatic acid- and aldehyde-responsive cluster at the dorsomedial part of the rat olfactory bulb. Homologous series of aliphatic acids and aldehydes were used for odorant stimulation. In response to adequate odorants, mitral cells showed spike responses with relatively low firing rates, whereas middle tufted cells responded with higher firing rates. Examination of the molecular receptive range (MRR) indicated that most mitral cells exhibited a robust inhibitory MRR, whereas a majority of middle tufted cells showed no or only a weak inhibitory MRR. In addition, structurally different odorants that activated neighboring clusters inhibited the spike activity of mitral cells, whereas they caused no or only a weak inhibition in the middle tufted cells. Furthermore, responses of mitral cells to an adequate excitatory odorant were greatly inhibited by mixing the odorant with other odorants that activated neighboring glomeruli. In contrast, odorants that activated neighboring glomeruli did not significantly inhibit the responses of middle tufted cells to the adequate excitatory odorant. These results indicate a clear difference between mitral and middle tufted cells in the manner of decoding the glomerular odor maps.

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