PMID- 28229459 OWN - NLM STAT- MEDLINE DCOM- 20180226 LR - 20181221 IS - 1469-7793 (Electronic) IS - 0022-3751 (Print) IS - 0022-3751 (Linking) VI - 595 IP - 11 DP - 2017 Jun 1 TI - Differential serotonergic modulation across the main and accessory olfactory bulbs. PG - 3515-3533 LID - 10.1113/JP273945 [doi] AB - KEY POINTS: There are serotonergic projections to both the main (MOB) and the accessory olfactory bulb (AOB). Current-clamp experiments demonstrate that serotonergic afferents are largely excitatory for mitral cells (MCs) in the MOB where 5-HT(2A) receptors mediate a direct excitatory action. Serotonergic afferents are predominately inhibitory for MCs in the AOB. There are two types of inhibition: indirect inhibition mediated through the 5-HT(2) receptors on GABAergic interneurons and direct inhibition via the 5-HT(1) receptors on MCs. Differential 5-HT neuromodulation of MCs across the MOB and AOB could contribute to select behaviours such as olfactory learning or aggression. ABSTRACT: Mitral cells (MCs) contained in the main (MOB) and accessory (AOB) olfactory bulb have distinct intrinsic membrane properties but the extent of neuromodulation across the two systems has not been widely explored. Herein, we investigated a widely distributed CNS modulator, serotonin (5-HT), for its ability to modulate the biophysical properties of MCs across the MOB and AOB, using an in vitro, brain slice approach in postnatal 15-30 day mice. In the MOB, 5-HT elicited three types of responses in 93% of 180 cells tested. Cells were either directly excited (70%), inhibited (10%) or showed a mixed response (13%)- first inhibition followed by excitation. In the AOB, 82% of 148 cells were inhibited with 18% of cells showing no response. Albeit located in parallel partitions of the olfactory system, 5-HT largely elicited MC excitation in the MOB while it evoked two different kinetic rates of MC inhibition in the AOB. Using a combination of pharmacological agents, we found that the MC excitatory responses in the MOB were mediated by 5-HT(2A) receptors through a direct activation. In comparison, 5-HT-evoked inhibitory responses in the AOB arose due to a polysynaptic, slow-onset inhibition attributed to 5-HT(2) receptor activation exciting GABAergic interneurons. The second type of inhibition had a rapid onset as a result of direct inhibition mediated by the 5-HT(1) class of receptors. The distinct serotonergic modulation of MCs between the MOB and AOB could provide a molecular basis for differential chemosensory behaviours driven by the brainstem raphe nuclei into these parallel systems. CI - (c) 2017 The Authors. The Journal of Physiology (c) 2017 The Physiological Society. FAU - Huang, Zhenbo AU - Huang Z AD - Program in Neuroscience, The Florida State University, Tallahassee, FL, USA. AD - Department of Biological Science, The Florida State University, Tallahassee, FL, USA. FAU - Thiebaud, Nicolas AU - Thiebaud N AD - Program in Neuroscience, The Florida State University, Tallahassee, FL, USA. AD - Department of Biological Science, The Florida State University, Tallahassee, FL, USA. FAU - Fadool, Debra Ann AU - Fadool DA AUID- ORCID: 0000-0002-0546-3720 AD - Program in Neuroscience, The Florida State University, Tallahassee, FL, USA. AD - Institute of Molecular Biophysics, The Florida State University, Tallahassee, FL, USA. AD - Department of Biological Science, The Florida State University, Tallahassee, FL, USA. LA - eng GR - R01 DC013080/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20170331 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - Female MH - Interneurons/metabolism/physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Olfactory Bulb/cytology/*metabolism/physiology MH - Receptor, Serotonin, 5-HT2A/metabolism MH - Sensory Receptor Cells/metabolism/physiology MH - Serotonergic Neurons/*metabolism/physiology MH - Serotonin/*metabolism MH - Synaptic Potentials PMC - PMC5451723 OTO - NOTNLM OT - 5-HT OT - mitral cell OT - olfaction OT - olfactory bulb OT - serotonin EDAT- 2017/02/24 06:00 MHDA- 2018/02/27 06:00 PMCR- 2018/06/01 CRDT- 2017/02/24 06:00 PHST- 2016/12/19 00:00 [received] PHST- 2017/02/12 00:00 [accepted] PHST- 2017/02/24 06:00 [pubmed] PHST- 2018/02/27 06:00 [medline] PHST- 2017/02/24 06:00 [entrez] PHST- 2018/06/01 00:00 [pmc-release] AID - TJP12295 [pii] AID - 10.1113/JP273945 [doi] PST - ppublish SO - J Physiol. 2017 Jun 1;595(11):3515-3533. doi: 10.1113/JP273945. Epub 2017 Mar 31.