Mitral Cells in the Olfactory Bulb Are Mainly Excited through a Multistep Signaling Path

Abstract

Within the olfactory system, information flow from the periphery onto output mitral cells (MCs) of the olfactory bulb (OB) has been thought to be mediated by direct synaptic inputs from olfactory sensory neurons (OSNs). Here, we performed patch-clamp measurements in rat and mouse OB slices to investigate mechanisms of OSN signaling onto MCs, including the assumption of a direct path, using electrical and optogenetic stimulation methods that selectively activated OSNs. We found that MCs are in fact not typically activated by direct OSN inputs and instead require a multistep, diffuse mechanism involving another glutamatergic cell-type, the tufted cells. The preference for a multi-step mechanism reflects the fact that signals arising from direct OSN inputs are drastically shunted by connexin 36-mediated gap junctions on MCs, but not tufted cells. An OB circuit with tufted cells intermediate between OSNs and MCs suggests that considerable processing of olfactory information occurs prior to it reaching MCs.

Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb

“…Model optimization led to closer matches to experimental data than for the ORN-MC circuit, and the ORN-PG-MC model with slow FFI exhibited substantial temporal sharpening of the sniff-triggered MC spike burst relative to the dynamics of ORN input (Fig. 3, F Gire et al 2012;Hayar et al 2004a;Najac et al 2011;Shao et al 2012). ET cells intrinsically burst at frequencies in the range of inhalation frequencies in behaving rodents, can be entrained to phasic ORN input, and have been hypothesized to play a critical role in maintaining MC patterning by providing direct excitation to MC, driving FFI of PG cells, or both (Gire et al 2012;Wachowiak and Shipley 2006).…”

“…3, F Gire et al 2012;Hayar et al 2004a;Najac et al 2011;Shao et al 2012). ET cells intrinsically burst at frequencies in the range of inhalation frequencies in behaving rodents, can be entrained to phasic ORN input, and have been hypothesized to play a critical role in maintaining MC patterning by providing direct excitation to MC, driving FFI of PG cells, or both (Gire et al 2012;Wachowiak and Shipley 2006). To our knowledge, however, bursting ET cells have not yet been incorporated into a network model of olfactory processing.…”

“…ORNs provide excitatory input to both MC and ET cells, although the degree to which MC excitation is mediated by ORN vs. ET cell input remains unclear (Gire et al 2012;Najac et al 2011;Shao et al 2012 explored the impact of different relative strengths of each pathway in shaping MC output dynamics. Relative strength was defined as the ratio of the charge per presynaptic action potential passed to the MC from ORNs directly vs. from the ET cell (see MATERIALS AND METHODS for details).…”

“…We used a smallnetwork modeling approach to reproduce key circuits in the OB network, focusing on well-described elements of the OB glomerular network, and asked how these elements, in isolation and integrated into multielement circuits, transform sniffdriven packets of sensory input into MC spiking responses. Recent experimental and theoretical studies have highlighted the importance of the glomerular circuitry in the larger OB network (De Saint Jan et al 2009;Gire et al 2012;Gire and Schoppa 2009;Hayar et al 2004a;Linster and Cleland 2009;Shao et al 2009Shao et al , 2012Wachowiak and Shipley 2006), but the exact roles that individual glomerular circuits of this network might play in shaping OB output in vivo remain unclear. The current study incorporates glomerular circuitry into a dynamic, biologically constrained network model and evaluates how the circuitry transforms sensory inputs in the temporal domain relative to sniffing.…”

“…The glomerular network includes connections between ORNs, MCs, several classes of GABAergic inhibitory interneurons and at least one type of excitatory interneuron (external tufted, or ET, cells) (Gire et al 2012;Gire and Schoppa 2009;Hayar et al 2004a;Shao et al 2009;Wachowiak and Shipley 2006). Glomerular circuits hypothesized to be important in shaping respiration-coupled MC response dynamics include feedforward excitation mediated by ET cells, feedforward intraglomerular inhibition mediated by periglomerular (PG) neurons, recurrent inhibition (RI) mediated by reciprocal connections between PG, ET and MCs, as well as interglomerular inhibitory connections formed by short-axon cells (Gire and Schoppa 2009;Liu et al 2013;Shao et al 2012Shao et al , 2013Wachowiak and Shipley 2006).…”