Dense encoding of natural odorants by ensembles of sparsely activated neurons in the olfactory bulb

Gschwend, Olivier; Beroud, Jonathan; Vincis, Roberto; Rodríguez, Iván; Carleton, Alan

doi:10.1038/srep36514

Cited by 19 publications

(16 citation statements)

References 40 publications

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“…In vivo electrophysiological recordings and analyses. Animals were prepared with a subcutaneous catheter (if planned for s.c. injections) and then fixed to a headrestraining device as previously described 38,39 . The cover slip protecting the brain was then taken out and the dura-matter removed under 1.5% isoflurane anaesthesia.…”

Section: Patchmentioning

confidence: 99%

Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia

Marissal¹,

Salazar

Bertollini

et al. 2017

Preprint

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Schizophrenia is a severely debilitating neurodevelopmental disorder. Establishing a causal link between circuit dysfunction and particular behavioural traits relevant to schizophrenia is crucial to shed new light on the mechanisms underlying the pathology. Here we studied an animal model of the 22q11 deletion syndrome, which is the highest genetic risk to develop the pathology. We report a desynchronization of hippocampal neuronal assemblies that resulted from parvalbumin interneuron hypoexcitability. Rescuing parvalbumin interneuron excitability with pharmacological or chemogenetic approaches is sufficient to restore wild type-like network dynamics and behaviour during adulthood. In conclusion, our data provide mechanistic insights underlying network dysfunction relevant to schizophrenia and demonstrate the potential of reverse engineering in fostering new therapeutic strategies to alleviate the burden of neurodevelopmental disorders.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/151795 doi: bioRxiv preprint first posted online 3 Main textAlterations of network dynamics have been proposed to be instrumental in schizophrenia [1][2][3] . A specific population of inhibitory neurons, the parvalbumin interneurons (PVIs), plays a key role in regulating network dynamics 4-7 and may be involved in the pathology [8][9][10][11] . Although specific manipulations of PVI can reproduce behavioural phenotypes relevant to schizophrenia in rodents 12,13 , it remains unclear whether PVI dysfunction is causally linked to network dysfunction and pathological behaviour associated with schizophrenia. More importantly, it is not known whether manipulating PVI could restore altered physiology.Among various genetic alterations, the specific deletion of ~30 genes on chromosome 22 that leads to the 22q11 deletion syndrome (22q11DS), is the highest identified genetic risk to develop schizophrenia 14,15 . We used a genetically engineered mouse bearing a hemizygous deletion on chromosome 16, termed Lgdel/+, which replicates the chromosomal alteration of the human 22q11DS 16 . In the CA1 area of the hippocampus, mouse models of 22q11DS differ from wild-type (WT) animals regarding their structural [17][18][19] and electrophysiological properties 20 , and their functional connectivity with distant brain areas 3 . We first tested whether those differences were accompanied by intrinsic differences in network dynamics. Neural activity was monitored in hippocampal slices using the genetically encoded calcium indicator GCaMP6s expressed by CA1 neurons following adeno-associated viral (AAV) vector transfection (Fig. 1a,b). Network dynamics were induced by bath application of carbachol (50 µM), which triggered spontaneous calcium activity in individual neurons of wild type (WT) mice 21,22 (Fig. 1c,d). Likewise, individual CA1neurons of Lgdel/+ mice exhibited spontaneous calcium activity during the duration ...

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Section: Patchmentioning

confidence: 99%

Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia

Marissal¹,

Salazar

Bertollini

et al. 2017

Preprint

Self Cite

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“…[25][26][27][28][29][30][31] The mitral/tufted cells (M/Ts) are the main output neurons of the OB, so factors that influence the normal circuits and activity of M/Ts may cause deficiencies in olfactory function. [25][26][27][28][29][30][31] The mitral/tufted cells (M/Ts) are the main output neurons of the OB, so factors that influence the normal circuits and activity of M/Ts may cause deficiencies in olfactory function.…”

mentioning

confidence: 99%

“…The OB is the first processing hub in the olfactory system and plays a key role in the representation of odor identity, intensity, and temporal information. [25][26][27][28][29][30][31] The mitral/tufted cells (M/Ts) are the main output neurons of the OB, so factors that influence the normal circuits and activity of M/Ts may cause deficiencies in olfactory function. [32][33][34] The mechanism by which insulin modulates the OB and the M/Ts has been extensively investigated in previous studies.…”

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confidence: 99%

Leptin modulates olfactory discrimination and neural activity in the olfactory bulb

Sun

Ke-ke

et al. 2019

Acta Physiologica

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Aim Leptin is an important peptide hormone that regulates food intake and plays a crucial role in modulating olfactory function. Although a few previous studies have investigated the effect of leptin on odor perception and discrimination in rodents, research on the neural basis underlying the behavioral changes is lacking. Here we study how leptin affects behavioral performance during a go/no‐go task and how it modulates neural activity of mitral/tufted cells in the olfactory bulb, which plays an important role in odor information processing and representation. Methods A go/no‐go odor discrimination task was used in the behavioral test. For in vivo studies, single unit recordings, local field potential recordings and fiber photometry recordings were used. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. Results Behaviorally, leptin affects performance and reaction time in a difficult odor‐discrimination task. Leptin decreases the spontaneous firing of single mitral/tufted cells, decreases the odor‐evoked beta and high gamma local field potential response, and has bidirectional effects on the odor‐evoked responses of single mitral/tufted cells. Leptin also inhibits the population calcium activity in genetically identified mitral/tufted cells and granule cells. Furthermore, in vitro slice recordings reveal that leptin inhibits mitral cell activity through direct modulation of the voltage‐sensitive potassium channel. Conclusions The behavioral reduction in odor discrimination observed after leptin administration is likely due to decreased neural activity in mitral/tufted cells, caused by modulation of potassium channels in these cells.

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“…Neural activity occurs within interconnected populations of neurons operating over a range of length scales and spatial locations throughout the brain. Recording sufficient numbers of neurons at natural timescales and spatial distributions is one of the foremost challenges for improved understanding of how neuronal ensembles operate in different behavioural states [1][2][3] . Optical methods are increasingly used in studies of network dynamics in vivo, as they permit the monitoring of activity over a large area from the same layer of brain tissue [4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Obaid

Hanna

et al. 2019

Preprint

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Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface. Figure 2: Microwire bundle fabrication. a, Fabrication procedure of microwire bundles. (i) Individual microwires are electrically insulated with a robust ceramic or polymeric coating. (ii) A sacrificial layer of parylene-C (PaC) is coated onto the wires to provide spacing. (iii) If desired, the tips of the microwires can be polished to an angular tip, or electrosharpened. (iv) The wires are then bundled together, either by spooling the wire, or mechanical aggregation. The wires naturally pack in a honeycomb array. (v)The bundle is infiltrated with biomedical epoxy to hold the wires together, then the top (proximal) end polished for mating to the CMOS chip. (vi) The proximal end is etched 10-20 µm to mate to the CMOS chip and the distal end of the wires is released by etching with oxygen plasma, allowing each wire to penetrate individually. A threaded collet is added to hold the bundle. b, A backscatter SEM of an individual microwire with a PtIr conductive core and 45 µm PaC coating (a, ii). c, The wires pack into a honeycomb structure, and epoxy is infiltrated in between to fill the gaps (a, v). d, The proximal end of a bundle of 177 20 µm Au wires with 100 µm spacing after etching to expose the conductive wire. e, The predicted volumetric displacement of bundles of microwires as a function of wire-to-wire distance, determined by the wire size and sacrificial coating thickness (t). This assumes a perfect hexagonal packing fraction of ~90.69%. For 15 µm wires with 100 µm spacing, the volume displaced is 2%. f, The distal end of a bundle of 600 7.5µm W wires coated with 1 µm of glass after etching to remove the PaC and embedded epoxy. g,h, The distal end (PtW 20 µm wires, 100 µm spacing) can be shaped with single wire precision to simultaneously access different depths in the tissue.

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Dense encoding of natural odorants by ensembles of sparsely activated neurons in the olfactory bulb

Cited by 19 publications

References 40 publications

Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia

Restoring wild type-like network dynamics and behaviour during adulthood in a mouse model of schizophrenia

Leptin modulates olfactory discrimination and neural activity in the olfactory bulb

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

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