Signaling between periglomerular cells reveals a bimodal role for GABA in modulating glomerular microcircuitry in the olfactory bulb

Abstract

In the mouse olfactory bulb glomerulus, the GABAergic periglomerular (PG) cells provide a major inhibitory drive within the microcircuit. Here we examine GABAergic synapses between these interneurons. At these synapses, GABA is depolarizing and exerts a bimodal control on excitability. In quiescent cells, activation of GABA A receptors can induce the cells to fire, thereby providing a means for amplification of GABA release in the glomerular microcircuit via GABA-induced GABA release. In contrast, GABA is inhibitory in neurons that are induced to fire tonically. PG-PG interactions are modulated by nicotinic acetylcholine receptors (nAChRs), and our data suggest that changes in intracellular calcium concentrations triggered by nAChR activation can be amplified by GABA release. Our results suggest that bidirectional control of inhibition in PG neurons can allow for modulatory inputs, like the cholinergic inputs from the basal forebrain, to determine threshold set points for filtering out weak olfactory inputs in the glomerular layer of the olfactory bulb via the activation of nAChRs.

Serotonin increases synaptic activity in olfactory bulb glomeruli

“…5HT increases both sEPSC and sIPSC frequency in PGCs and SACs. Moreover, GABA may inhibit, shunt, or even excite glomerular interneurons (Parsa et al 2015). Thus it is not obvious how 5HT might 5HT-evoked responses in SACs.…”

“…A striking feature of OB circuitry is the prominence of dendrodendritic synapses in addition to classical axodendritic synapses (Hinds 1970;Pinching and Powell 1971a,b;White 1973;Kasowski et al 1999;Kosaka and Kosaka 2011). Dendrodendritic synapses can support action potential-independent neurotransmission between MCs and granule cells (Jahr and Nicoll 1980;Shepherd 1998) and among neurons in the glomerular layer (Aroniadou-Anderjaska et al 1999;Murphy et al 2005;Masurkar and Chen 2012;D'Souza et al 2013;Fekete et al 2014;Liu et al 2015;Parsa et al 2015).…”

“…Although serotonin increases sEPSCs and sIPSCs in both PGCs and SACs, the two cell types may integrate these inputs differently due to differences in intrinsic properties. Moreover, GABAergic synapses in glomerular interneurons may be inhibitory, shunting or even excitatory (Parsa et al 2015). To better understand how 5HT modulates glomerular circuit processing, more knowledge of intrinsic and synaptic properties of glomerular interneurons is needed.…”

Basal forebrain GABAergic innervation of olfactory bulb periglomerular interneurons

“…Each cells was stimulated with 5 flashes of light at 20 Hz. Lines connect plots from 309 the same cells.310Functional implications of basal forebrain GABAergic inputs312 Previous studies found that the chloride concentration is high in PG cells and,313 consequently, that GABA is depolarizing(Smith and Jahr, 2002;Parsa et al, 2015). The net 314 impact of GABA is, however, still unclear as one study concluded that GABA inhibits the firing315 of PG cells by shunting excitatory inputs (Smith and Jahr, 2002) whereas the other found 316 that GABA is excitatory and induces the firing of PG cells (Parsa et al, 2015).…”

Possible role of calcitonin gene‐related peptide in trigeminal modulation of glomerular microcircuits of the rodent olfactory bulb

“…This bottom-up processing of afferent signals is controlled by modulatory top-down signals, which reach the olfactory bulb from various cortical areas and other brain regions through centrifugal innervation (Matsutani & Yamamoto, 2008;Mouret et al, 2009;Boyd et al, 2012;Nunez-Parra et al, 2013). Cholinergic, serotonergic and adrenergic neuromodulation of bulb circuits have recently been examined in detail (Li & Cleland, 2013;Devore et al, 2014;Eckmeier & Shea, 2014;Rothermel et al, 2014;Schmidt & Strowbridge, 2014;Liu et al, 2015;Parsa et al, 2015;Smith et al, 2015;Brill et al, 2016;Kapoor et al, 2016), and other systems contribute as well (Tobin et al, 2010;Ma et al, 2013).…”