Local Postsynaptic Voltage-Gated Sodium Channel Activation in Dendritic Spines of Olfactory Bulb Granule Cells

Bywalez, Wolfgang; Patirniche, Dinu; Rupprecht, Vanessa; Stemmler, Martin B.; Herz, Andreas V. M.; Pálfi, Dénes; Rózsa, Balázs; Egger, Veronica

doi:10.1016/j.neuron.2016.02.029

Cited by 11 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since GCs release neurotransmitter from their dendrites, their output can be modulated by local depolarization as well as cell-wide depolarization. Experiments in slices have indicated that both modes of depolarization can exist (Bywalez et al, 2015;Egger et al, 2005), but the occurrence of dendritic depolarization in vivo has remained in question. Imaging allowed us to examine directly how the apical dendrites of GCs respond to odorants.…”

Section: Dendritic Responsesmentioning

confidence: 99%

“…In addition, since GCs can release transmitter even in the absence of action potentials (Isaacson and Strowbridge, 1998;Jahr and Nicoll, 1980;Schoppa et al, 1998), they are capable of local dendritic processing in addition to cellwide activation (Bywalez et al, 2015;Egger et al, 2003Egger et al, , 2005Zelles et al, 2006). The extent to which such local processing, which could have important consequences for the computational capabilities of the OB (Bywalez et al, 2015;McTavish et al, 2012;Wiechert et al, 2010), occurs in vivo remains unknown. In addition to feed-forward sensory inputs, GCs also receive extensive feedback from olfactory cortical areas (Boyd et al, 2012;Davis and Macrides, 1981;Markopoulos et al, 2012;Strowbridge, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb

Wienisch

Murthy

2016

Preprint

View full text Add to dashboard Cite

Information processing in early sensory regions is modulated by a diverse range of inhibitory interneurons. We sought to elucidate the role of olfactory bulb interneurons called granule cells (GCs) in odor processing by imaging the activity of hundreds of these cells simultaneously in mice. Odor responses in GCs were temporally diverse and spatially disperse, with some degree of non-random, modular organization. The overall sparseness of activation of GCs was highly correlated with the extent of glomerular activation by odor stimuli. Increasing concentrations of single odorants led to proportionately larger population activity, but some individual GCs had non-monotonic relation to concentration due to local inhibitory interactions. Individual dendritic segments could sometimes respond independently to odors, revealing their capacity for compartmentalized signaling in vivo. Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons.

show abstract

Section: Dendritic Responsesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb

Wienisch

Murthy

2016

Preprint

View full text Add to dashboard Cite

show abstract

“…Since natural vomeronasal social cues are only known to exist in the form of such complex blends, the difference in monomolecular tuning sparseness between AOB EGCs and MOB PV-EPL interneurons and AOB EGCs might reflect macroscopic differences in the natural statistics of ligand sampling between these two chemosensory pathways. It may also be the case that MC inhibition by EGCs takes place locally at reciprocal dendrodendritic synapses in a spiking-independent manner, as has been observed in the MOB (Isaacson and Strowbridge, 1998;Schoppa et al, 1998;Chen et al, 2000;Halabisky et al, 2000;Isaacson, 2001;Egger et al, 2005;Bywalez et al, 2015;Lage-Rupprecht et al, 2018).…”

Section: Implications For Models Of Aob Information Processingmentioning

confidence: 85%

“…The lack of broadly tuned spiking activity does not support divisive normalization in the context of small numbers of odorants. Instead, these data suggest that EGCs inhibit MCs in specific chemosensory conditions involving rich pheromone environments or perhaps that they modulate MC activity through spiking-independent mechanisms (Isaacson and Strowbridge, 1998;Schoppa et al, 1998;Chen et al, 2000;Halabisky et al, 2000;Isaacson, 2001;Egger et al, 2005;Bywalez et al, 2015;Lage-Rupprecht et al, 2018). These studies provide new information about the role of AOB EGCs in AOS sensory processing, and place important constraints on our models of AOB circuit function.…”

Section: Introductionmentioning

confidence: 98%

Paradoxically sparse chemosensory tuning in broadly-integrating external granule cells in the mouse accessory olfactory bulb

Zhang

Meeks

2019

Preprint

View full text Add to dashboard Cite

The accessory olfactory bulb (AOB) is a critical circuit in the mouse accessory olfactory system (AOS), but AOB processing is poorly understood compared to the main olfactory bulb (MOB). We used 2-photon GCaMP6f Ca 2+ imaging in an ex vivo preparation to study the chemosensory tuning of AOB external granule cells (EGCs), an interneuron population hypothesized to broadly integrate from mitral cells (MCs). We measured MC and EGC tuning to natural chemosignal blends and monomolecular ligands, finding that EGC tuning was far sparser than MC tuning. Simultaneous patch-clamp electrophysiology and Ca 2+ imaging indicated that this was only partially explained by lower GCaMP6f-to-spiking ratios in EGCs compared to MCs. Ex vivo patch-clamp recordings revealed that EGC subthreshold responsivity was broad, but monomolecular ligand responses were insufficient to elicit spiking. These results indicate that EGC spiking is selectively engaged by chemosensory blends, suggesting different roles for EGCs than analogous interneurons in the MOB. 2005; Kaba and Huang, 2005; Araneda and Firestein, 2006; Hendrickson et al., 2008; Cansler et al., 2017; Gao et al., 2017). Cumulatively, these observations suggest that MC-interneuron communication in the AOB is critical for rodent physiology and behavior. Despite recent progress, many gaps in our understanding of AOB MC-interneuron interactions remain. A major limitation for our understanding of AOB function is a lack of information about how MCs interact with several inhibitory neural types. The AOB has a variety of interneurons that have been largely classified based on their location and morphology (Larriva-Sahd, 2008; Moriya-Ito et al., 2013). Three major AOB interneuron types have been identified, along with several minor types. Juxtaglomerular cells (JGCs) are found within the superficial glomerular layer, where excitatory sensory inputs from the vomeronasal organ (VNO) enter the AOB. External granule cells (EGC) are found in the external cell layer alongside the somas of MCs. Internal granule cells (IGCs), the most abundant and well-studied AOB interneuron type, are located in the internal granule layer. JGCs, similar to counterparts in the main olfactory bulb (MOB), are thought to modulate the input to the MCs via their synaptic connection with VNO axon terminals and MC apical dendrites within glomeruli (Geramita and Urban, 2017). EGCs and IGCs, in contrast, are thought to modulate MC activity via reciprocal dendrodendritic connections (Taniguchi and Kaba, 2001; Castro et al., 2007). Relative to JGCs and IGCs, there is very little information about the physiology or function of AOB EGCs; just one targeted study of their intrinsic features has been reported (Maksimova et al., 2019).Cells that appear analogous to AOB EGCs have been studied in the MOB. Specifically, MOB parvalbumin-expressing interneurons in the external plexiform layer (PV-EPL interneurons) resemble EGCs in their morphologies and apparent broad connectivity with MCs. These MOB PV-EPL interneurons were shown to integr...

show abstract

“…Though the complex as a whole is undescribed, several members are known to interact, physically or functionally. For instance, N-cadherin and AMPA receptors interact at the cell surface (Nuriya and Huganir, 2006;Saglietti et al, 2007;Silverman et al, 2007) , AMPA receptors and Na v channels are both involved in postsynaptic depolarization (Bywalez et al, 2015;Lage-Rupprecht et al, 2019) , and EFR3b is a membrane scaffolding protein involved in the synthesis of PIP2, a lipid that regulates AMPA receptor activity (Seebohm et al, 2014) and trafficking (McCartney et al, 2014) . In flies, knock-down of the EFR3 homolog "rolling blackout" severely affects neuronal function, but primarily in the pre-synapse (Huang et al, 2004(Huang et al, , 2006 .…”

Section: Co-fractionation Broadly Recovers Neural Protein Complexesmentioning

confidence: 99%

Mapping Functional Protein Neighborhoods in the Mouse Brain

Liebeskind

Young

Halling

et al. 2020

Preprint

View full text Add to dashboard Cite

New proteomics methods make it possible to determine protein interaction maps at the proteome scale without the need for genetically encoded tags, opening up new organisms and tissue types to investigation. Current molecular and computational methods are oriented towards protein complexes that are soluble, stable, and discrete. However, the mammalian brain, among the most complicated and most heavily studied tissue types, derives many of its unique functions from protein interactions that are neither discrete nor soluble. Proteomics investigations into the global protein interaction landscape of the brain have therefore leveraged non-proteomics datasets to supplement their experiments. Here, we develop a novel, integrative proteomics pipeline and apply it to infer a global map of functional protein neighborhoods in the mouse brain without the aid of external datasets. By leveraging synaptosome enrichment and interactomics methods that target both soluble and insoluble protein fractions, we resolved protein interactions for key neural pathways, including those from refractory subcellular fractions such as the membrane and cytoskeleton. In comparison to external datasets, our observed interactions perform similarly to hand-curated synaptic protein interactions while also suggesting thousands of novel connections. We additionally employed cleavable chemical cross-linkers to detect direct binding partners and provide structural context. Our combined map suggests new protein pathways and novel mechanisms for proteins that underlie neurological diseases, including autism and epilepsy. Our results show that proteomics methods alone are sufficient to determine global interaction maps for proteins that are of broad interest to neuroscience. We anticipate that our map will be used to prioritize new research avenues and will pave the way towards future proteomics techniques that resolve protein interactions at ever greater resolution.

show abstract

Local Postsynaptic Voltage-Gated Sodium Channel Activation in Dendritic Spines of Olfactory Bulb Granule Cells

Cited by 11 publications

References 0 publications

Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb

Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb

Paradoxically sparse chemosensory tuning in broadly-integrating external granule cells in the mouse accessory olfactory bulb

Mapping Functional Protein Neighborhoods in the Mouse Brain

Contact Info

Product

Resources

About