Structured spike series specify gene expression patterns for olfactory circuit formation

Nakashima, Ai; Ihara, Naoki; Shigeta, Mayo; Kanazawa, Hiroshi; Ikegaya, Yuji; Takeuchi, Haruki

doi:10.1126/science.aaw5030

Cited by 56 publications

(66 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, it was puzzling that PEA exposure would increase the number of TAAR4 glomeruli as odor experience had been shown to facilitate the convergence of axons (Zou et al, 2004). Neural activity influences gene expression in the OSNs during development (Connelly et al, 2013;Inoue et al, 2018;Nakashima et al, 2019;Serizawa et al, 2006). Specific patterns of activity have been associated with the expression of axon guidance molecules that determine target specificity of the OSNs (Nakashima et al, 2013).…”

Section: Transcriptomic Changes In Response To Silencing and Activationmentioning

confidence: 99%

“…In postnatal development of the olfactory system, OSNs fire spontaneous action potentials originating from ligandindependent activities (Nakashima et al, 2013;Yu et al, 2004). The receptor activities drive specific temporal patterns of action potential firing (Nakashima et al, 2019). Spontaneous activity influences the development of the olfactory glomerular map during the critical period (Ma et al, 2014;Tsai and Barnea, 2014;Wu et al, 2018), which persists into adulthood.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

Qiu

et al. 2021

eLife

View full text Add to dashboard Cite

Animals possess an inborn ability to recognize certain odors to avoid predators, seek food and find mates. Innate odor preference has been thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Moreover, exposure to an aversive odor during the critical period abolishes aversion in adulthood in an odor-specific manner. The loss of innate aversion is associated with broadened projection of OSNs. Thus, a delicate balance of neural activity is required during the critical period in establishing innate odor preference and ectopic projection is a convergent mechanism to alter innate odor valence.

show abstract

Section: Transcriptomic Changes In Response To Silencing and Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

Qiu

et al. 2021

eLife

View full text Add to dashboard Cite

show abstract

“…Indeed, stomatin, another protein of the same family that also contains the stomatin motif, has already been shown to interact with GPCRs (Wang et al, 2014;Park et al, 2016), thus making it possible that STOML3 might also function similarly in OSNs. In particular, it could regulate OR assembly on the ciliary membrane by mitigating the translocation of ORs with medium/high basal activity to keep basal noise instructive without altering the signal-to-noise ratio in OSNs (Nakashima et al, 2019). Indeed, a higher basal rate of constitutive activity could result in an increased cAMP production rate that would likely keep the cell in a more adapted state, thus limiting action potential firing (as we observed in Stoml3 KO neurons).…”

Section: Discussionmentioning

confidence: 89%

A Role for STOML3 in Olfactory Sensory Transduction

Agostinelli

Gonzalez-Velandia

Hernandez-Clavijo

et al. 2021

eNeuro

View full text Add to dashboard Cite

Stomatin-like protein-3 (STOML3) is an integral membrane protein expressed in the cilia of olfactory sensory neurons, but its functional role in this cell type has never been addressed. STOML3 is also expressed in dorsal root ganglia neurons, where it has been shown to be required for normal touch sensation. Here, we extended previous results indicating that STOML3 is mainly expressed in the knob and proximal cilia of olfactory sensory neurons. We additionally showed that mice lacking STOML3 have a morphologically normal olfactory epithelium. Due to its presence in the cilia, together with known olfactory transduction components, we hypothesized that STOML3 could be involved in modulating odorant responses in olfactory sensory neurons. To investigate the functional role of STOML3, we performed loose patch recordings from wild type and Stoml3 KO olfactory sensory neurons. We found that spontaneous mean firing activity was lower with additional shift in interspike intervals distributions in Stoml3 KOs compared to wild type neurons. Moreover, the firing activity in response to stimuli was reduced both in spike number and duration in neurons lacking STOML3 compared to wildtype neurons. Control experiments suggested that the primary deficit in neurons lacking STOML3 was at the level of transduction and not at the level of action potential generation. We conclude that STOML3 has a physiological role in olfaction, being required for normal sensory encoding by olfactory sensory neurons. Significance Statement Olfactory transduction comprises a series of well-characterized molecular steps that take place in the cilia of olfactory sensory neurons (OSNs) terminating in action potential firing. Here, we introduce a possible new player: stomatin-like protein 3 (STOML3). Indeed, STOML3 is localized in olfactory cilia, and we show that STOML3 plays a role in OSN physiology. First, it allows OSNs to broaden the possible frequency range of their spontaneous activity. Second, STOML3 modulates odorant-evoked action potential firing by regulating both the number of spikes and response duration. These new findings call for a reconsideration of the patterns of the peripheral coding of sensory stimuli. MATERIALS AND METHODS Animals Mice were handled in accordance with the Italian Guidelines for the Use of Laboratory Animals and the European Union guidelines on animal research according to a protocol approved by the ethics committee [Author Institute]. Experiments were performed on tissues from C57BL/6 WT and Stoml3 KO mice of either sex (Wetzel et al., 2007). Immunohistochemistry The head containing the nasal cavity was fixed in 4% paraformaldehyde in PBS at pH 7.4 for 4 hours at 4°C. After fixing, the heads of the mice were incubated in 0.5 M EDTA for 2 days. The tissues were cryoprotected by incubation in 30% sucrose in PBS at pH 7.4 overnight. The tissue was immersed in cryostat embedding medium (BioOptica) and immediately frozen at −80°C. Coronal sections (16-18 μm) were cut on a cryostat and mounted on Superfrost Plus Adhesion Mic...

show abstract

“…and Kirrel3 have chemically incompatible interface sequences similar to mouse Kirrels and that extant jawed fish Kirrel sequences also follow these patterns, Kirrel specialization must have appeared early in gnathostomes and before the rise of distinct accessory olfactory systems and several expansions in olfactory receptor gene families (Bear et al, 2016;Poncelet and Shimeld, 2020 (Brignall et al, 2018;Nakashima et al, 2019;Prince et al, 2013;Vaddadi et al, 2019), and Kirrel3 knockout mice show behavioral abnormalities similar to those in autistic patients, including defects in social responses, auditory sensory processing and communication, and repetitive behaviors (Hisaoka et al, 2018;Völker et al, 2018), in addition to loss of male-male aggression likely as a result of miswiring in the AOB (Prince et al, 2013). Furthermore, several mutations in human autism and intellectual disability patients were identified (see Taylor et al., 2020 for a list).…”

Section: Discussionmentioning

confidence: 99%

Molecular and Structural Basis of Olfactory Sensory Neuron Coalescence by Kirrel Receptors

Wang

Vaddadi

Pak

et al. 2021

Preprint

View full text Add to dashboard Cite

Projections from sensory neurons of olfactory systems coalesce into glomeruli in the brain. The Kirrel receptors are believed to homodimerize via their ectodomains and help separate sensory neuron axons into Kirrel2- or Kirrel3-expressing glomeruli. Here we present the crystal structures of homodimeric Kirrel receptors and show that the closely related Kirrel2 and Kirrel3 have evolved specific sets of polar and hydrophobic interactions, respectively, disallowing heterodimerization while preserving homodimerization, likely resulting in proper segregation and coalescence of Kirrel-expressing axons into glomeruli. We show that the dimerization interface at the N-terminal IG domains is necessary and sufficient to create homodimers, and fail to find evidence for a secondary interaction site in Kirrel ectodomains. Furthermore, we show that abolishing dimerization of Kirrel3 in vivo leads to improper formation of glomeruli in the mouse accessory olfactory bulb as observed in Kirrel3-/- animals. Our results provide strong evidence for Kirrel3 homodimerization controlling axonal coalescence.

show abstract

Structured spike series specify gene expression patterns for olfactory circuit formation

Cited by 56 publications

References 62 publications

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

Acquisition of innate odor preference depends on spontaneous and experiential activities during critical period

A Role for STOML3 in Olfactory Sensory Transduction

Molecular and Structural Basis of Olfactory Sensory Neuron Coalescence by Kirrel Receptors

Contact Info

Product

Resources

About