PMID- 32503886 OWN - NLM STAT- MEDLINE DCOM- 20201123 LR - 20240329 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 40 IP - 27 DP - 2020 Jul 1 TI - Paradoxically Sparse Chemosensory Tuning in Broadly Integrating External Granule Cells in the Mouse Accessory Olfactory Bulb. PG - 5247-5263 LID - 10.1523/JNEUROSCI.2238-19.2020 [doi] AB - The accessory olfactory bulb (AOB), the first neural circuit in the mouse accessory olfactory system, is critical for interpreting social chemosignals. Despite its importance, AOB information processing is poorly understood compared with the main olfactory bulb (MOB). Here, we sought to fill gaps in the understanding of AOB interneuron function. We used 2-photon GCaMP6f Ca(2+) imaging in an ex vivo preparation to study chemosensory tuning in AOB external granule cells (EGCs), interneurons hypothesized to broadly inhibit activity in excitatory mitral cells (MCs). In ex vivo preparations from mice of both sexes, we measured MC and EGC tuning to natural chemosignal blends and monomolecular ligands, finding that EGC tuning was sparser, not broader, than upstream MCs. Simultaneous electrophysiological recording and Ca(2+) imaging showed no differences in GCaMP6f-to-spiking relationships in these cell types during simulated sensory stimulation, suggesting that measured EGC sparseness was not due to cell type-dependent variability in GCaMP6f performance. Ex vivo patch-clamp recordings revealed that EGC subthreshold responsivity was far broader than indicated by GCaMP6f Ca(2+) imaging, and that monomolecular ligands rarely elicited EGC spiking. These results indicate that EGCs are selectively engaged by chemosensory blends, suggesting different roles for EGCs than analogous interneurons in the MOB.SIGNIFICANCE STATEMENT The mouse accessory olfactory system (AOS) interprets social chemosignals, but we poorly understand AOS information processing. Here, we investigate the functional properties of external granule cells (EGCs), a major class of interneurons in the accessory olfactory bulb (AOB). We hypothesized that EGCs, which are densely innervated by excitatory mitral cells (MCs), would show broad chemosensory tuning, suggesting a role in divisive normalization. Using ex vivo GCaMP6f imaging, we found that EGCs were instead more sparsely tuned than MCs. This was not due to weaker GCaMP6f signaling in EGCs than in MCs. Instead, we found that many MC-activating chemosignals caused only subthreshold EGC responses. This indicates a different role for AOB EGCs compared with analogous cells in the main olfactory bulb. CI - Copyright (c) 2020 Zhang and Meeks. FAU - Zhang, Xingjian AU - Zhang X AD - University of Texas Southwestern Medical Center, Dallas, Texas 75390. FAU - Meeks, Julian P AU - Meeks JP AUID- ORCID: 0000-0002-7537-4491 AD - University of Texas Southwestern Medical Center, Dallas, Texas 75390 Julian_Meeks@urmc.rochester.edu. AD - University of Rochester School of Medicine and Dentistry, Rochester, NY, 14642. LA - eng GR - R01 DC015784/DC/NIDCD NIH HHS/United States GR - R01 DC017985/DC/NIDCD NIH HHS/United States GR - R21 NS104826/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200605 PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/physiology MH - Cytoplasmic Granules MH - Electrophysiological Phenomena/physiology MH - Female MH - Interneurons/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neuroimaging MH - Odorants MH - Olfactory Bulb/*cytology/*physiology MH - Patch-Clamp Techniques MH - Smell/*physiology MH - Vomeronasal Organ/cytology/physiology PMC - PMC7329303 OTO - NOTNLM OT - accessory olfactory system OT - chemical senses OT - interneuron OT - olfaction OT - sensory processing OT - vomeronasal system EDAT- 2020/06/07 06:00 MHDA- 2020/11/24 06:00 PMCR- 2020/07/01 CRDT- 2020/06/07 06:00 PHST- 2019/09/16 00:00 [received] PHST- 2020/04/20 00:00 [revised] PHST- 2020/04/23 00:00 [accepted] PHST- 2020/06/07 06:00 [pubmed] PHST- 2020/11/24 06:00 [medline] PHST- 2020/06/07 06:00 [entrez] PHST- 2020/07/01 00:00 [pmc-release] AID - JNEUROSCI.2238-19.2020 [pii] AID - JN-RM-2238-19 [pii] AID - 10.1523/JNEUROSCI.2238-19.2020 [doi] PST - ppublish SO - J Neurosci. 2020 Jul 1;40(27):5247-5263. doi: 10.1523/JNEUROSCI.2238-19.2020. Epub 2020 Jun 5.