Serotonin increases synaptic activity in olfactory bulb glomeruli

Abstract

Serotoninergic fibers densely innervate olfactory bulb glomeruli, the first sites of synaptic integration in the olfactory system. Acting through 5HT2A receptors, serotonin (5HT) directly excites external tufted cells (ETCs), key excitatory glomerular neurons, and depolarizes some mitral cells (MCs), the olfactory bulb's main output neurons. We further investigated 5HT action on MCs and determined its effects on the two major classes of glomerular interneurons: GABAergic/dopaminergic short axon cells (SACs) and GABAergic periglomerular cells (PGCs). In SACs, 5HT evoked a depolarizing current mediated by 5HT2C receptors but did not significantly impact spike rate. 5HT had no measurable direct effect in PGCs. Serotonin increased spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) in PGCs and SACs. Increased sEPSCs were mediated by 5HT2A receptors, suggesting that they are primarily due to enhanced excitatory drive from ETCs. Increased sIPSCs resulted from elevated excitatory drive onto GABAergic interneurons and augmented GABA release from SACs. Serotonin-mediated GABA release from SACs was action potential independent and significantly increased miniature IPSC frequency in glomerular neurons. When focally applied to a glomerulus, 5HT increased MC spontaneous firing greater than twofold but did not increase olfactory nerve-evoked responses. Taken together, 5HT modulates glomerular network activity in several ways: 1) it increases ETC-mediated feed-forward excitation onto MCs, SACs, and PGCs; 2) it increases inhibition of glomerular interneurons; 3) it directly triggers action potential-independent GABA release from SACs; and 4) these network actions increase spontaneous MC firing without enhancing responses to suprathreshold sensory input. This may enhance MC sensitivity while maintaining dynamic range.

Differential serotonergic modulation across the main and accessory olfactory bulbs

“…Recently Brill et al . () electrophysiologically applied a different cadre of antagonists to model the dense serotonergic innervation of the MOB to synaptic contacts on MCs (5‐HT 2A subtype), external tufted cells (5‐HT 2A subtype) and SACs (5HT 2C subtype) to suggest an increased excitatory drive onto glomerular interneurons due to 5HT 2A subtype activation on MCs. Although there is no reported expression of subtype‐specific receptors in the AOB, apart from the reported lack of 5‐HT 2A mRNA by McLean et al .…”

“…; Brill et al . ). In our studies, 20 μ m 5‐HT was used for MOB MC recordings whereas 40 μ m was used for AOB MC recordings.…”

Dendritic Arborization Patterns of Small Juxtaglomerular Cell Subtypes within the Rodent Olfactory Bulb

“…Whether this slow decay is a result of slow extrusion or a very high buffering capacity remains to be elucidated. Dopaminergic JGCs have been shown to independently release GABA and dopamine from their dendrites (Borisovska et al, 2013; Brill et al, 2016). If dopamine gets released only upon sufficiently strong or prolonged stimulation (Maher and Westbrook, 2008; Bundschuh et al, 2012), it is interesting to note that the remarkably slow decay of Ca 2+ reported here will result in strong summation of both postsynaptic and AP-evoked Ca 2+ transients within a time frame of seconds.…”

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis

“…Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function (McLean et al, 1993; Aungst and Shipley, 2005; Hardy et al, 2005; Petzold et al, 2009; Liu et al, 2011a; Schmidt and Strowbridge, 2014; Brill et al, 2016; Brunert et al, 2016; Kapoor et al, 2016; Linster and Cleland, 2016; Lottem et al, 2016). For instance, electrical stimulation of the raphe nuclei modulates the level of odor information input into the olfactory bulb (Petzold et al, 2009).…”