Two GABAergic Intraglomerular Circuits Differentially Regulate Tonic and Phasic Presynaptic Inhibition of Olfactory Nerve Terminals

Abstract

Olfactory nerve axons terminate in olfactory bulb glomeruli forming excitatory synapses onto the dendrites of mitral/tufted (M/T) and juxtaglomerular cells, including external tufted (ET) and periglomerular (PG) cells. PG cells are heterogeneous in neurochemical expression and synaptic organization. We used a line of mice expressing green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa gene (GAD65+) promoter to characterize a neurochemically identified subpopulation of PG cells by whole cell recording and subsequent morphological reconstruction. GAD65+ GABAergic PG cells form two functionally distinct populations: 33% are driven by monosynaptic olfactory nerve (ON) input (ON-driven PG cells), the remaining 67% receive their strongest drive from an ON→ET→PG circuit with no or weak monosynaptic ON input (ET-driven PG cells). In response to ON stimulation, ON-driven PG cells exhibit paired-pulse depression (PPD), which is partially reversed by GABAB receptor antagonists. The ON→ET→PG circuit exhibits phasic GABAB-R-independent PPD. ON input to both circuits is under tonic GABAB-R-dependent inhibition. We hypothesize that this tonic GABABR-dependent presynaptic inhibition of olfactory nerve terminals is due to autonomous bursting of ET cells in the ON→ET→PG circuit, which drives tonic spontaneous GABA release from ET-driven PG cells. Both circuits likely produce tonic and phasic postsynaptic inhibition of other intraglomerular targets. Thus olfactory bulb glomeruli contain at least two functionally distinct GABAergic circuits that may play different roles in olfactory coding.

Intraglomerular Lateral Inhibition Promotes Spike Timing Variability in Principal Neurons of the Olfactory Bulb

“…At V h ϭ Ϫ75 mV, the AMPA receptor antagonist NBQX (10 M) abolished evoked EPSCs (n ϭ 3; data not shown), whereas at V h ϭ 30 mV, addition of the NMDA receptor antagonist d-AP-5 (50 M) was required to block the EPSC (n ϭ 4; data not shown). As reported previously (Shao et al, 2009), the latency of the first EPSC and the jitter of the latency depended on the intensity of stimulation (Fig. 1E).…”

“…However, PG cells may provide as much as 50% of their inhibitory inputs (Dong et al, 2007), and recent evidence suggest that a stimulation of OSNs evokes a potent intraglomerular inhibition in mitral cells (Najac et al, 2011;Shao et al, 2012). However, PG cells constitute a diverse population of interneurons with different membrane properties (McQuiston and Katz, 2001;Hayar et al, 2004;Murphy et al, 2005;Shao et al, 2009), morphologies (Pinching and Powell, 1971b;Hayar et al, 2004;Kiyokage et al, 2010;Kosaka and Kosaka, 2010), and immunohistochemical properties (Kosaka and Kosaka, 2007;Panzanelli et al, 2007;Parrish-Aungst et al, 2007;Whitman and Greer, 2007), suggesting that each subtype may form circuits playing different functions.…”

Differences in Glomerular-Layer-Mediated Feedforward Inhibition onto Mitral and Tufted Cells Lead to Distinct Modes of Intensity Coding

“…6i). Finally, significant tonic inhibition exists within the glomerular circuit (Aroniadou-Anderjaska et al, 2000;Shao et al, 2009) and could contribute to differences in stimulus-evoked responses. Therefore, we compared spontaneous activity in MCs and TCs before and after puffing gabazine into the glomerulus (Fig.…”

“…Subsets of PGCs have been identified both functionally and molecularly. Functionally, PGCs are classified by whether they receive excitation from OSNs or ETCs (Hayar et al, 2004;Shao et al, 2009). In addition, PGCs are molecularly heterogeneous (Kosaka et al, 1998;Parrish-Aungst et al, 2007;Kiyokage et al, 2010).…”

Interdependent Conductances Drive Infraslow Intrinsic Rhythmogenesis in a Subset of Accessory Olfactory Bulb Projection Neurons

“…This morphology indicates that sensory computation in AOB mitral cells is fundamentally different from the processing of "glomerulus-specific" information by their MOB counterparts (Dulac and Torello, 2003). Despite important recent insights into the organizational principles of connectivity, sensory input, and integration in the AOB (Del Punta et al, 2002;Ma and Lowe, 2004;Sugai et al, 2005;Castro et al, 2007;Ben-Shaul et al, 2010;Smith and Araneda, 2010;Hovis et al, 2012;Leszkowicz et al, 2012;Shpak et al, 2012;Tolokh et al, 2013;Hammen et al, 2014), a conceptual understanding of how the biophysical properties of AOB mitral cells affect their computations is lacking.…”