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.

Summary Sensory perception is not a simple feed-forward process and higher brain areas can actively modulate information processing in “lower” areas. We used optogenetic methods to examine how cortical feedback projections affect circuits in the first olfactory processing stage, the olfactory bulb. Selective activation of back projections from the anterior olfactory nucleus/cortex (AON) revealed functional glutamatergic synaptic connections on several types of bulbar interneurons. Unexpectedly, AON axons also directly depolarized mitral cells, enough to elicit spikes reliably in a time window of a few milliseconds. Mitral cells received strong disynaptic inhibition, a third of which arises in the glomerular layer. Activating feedback axons in vivo led to suppression of spontaneous as well as odor-evoked activity of mitral cells, sometimes preceded by a temporally-precise increase in firing probability. Our study indicates that cortical feedback can shape the activity of bulbar output neurons by enabling precisely timed spikes and enforcing broad inhibition to suppress background activity.

Odors are coded at the input level of the olfactory bulb by a spatial map of activated glomeruli, reflecting different odorant receptors (ORs) stimulated in the nose. Here we examined the function of local synaptic processing within glomeruli in transforming these input patterns into an output for the bulb, using patch-clamp recordings and calcium imaging in rat bulb slices. Two types of transformations were observed at glomeruli, the first of which produced a bimodal, "on/off" glomerular signal that varied probabilistically depending on olfactory receptor neuron (ORN) input levels. The bimodal response behavior was seen in glomerular synaptic responses, as well as in action potential ("spike") firing, wherein all mitral cells affiliated with a glomerulus either engaged in prolonged spike bursts or did not spike at all. In addition, evidence was obtained that GABAergic periglomerular (PG) cells that surround a glomerulus can prevent activation of a glomerulus through inhibitory inputs targeted onto excitatory external tufted cells. The path of PG cell activation appeared to be confined to one glomerulus, such that ORNs at one glomerulus initiated inhibition of the same glomerulus. The observed glomerular "self-inhibition" provides a mechanism of filtering odor signals that would be an alternative to commonly proposed mechanisms of lateral inhibition between OR-specific glomeruli. In this case, selective suppression of weak odor signals could be achieved based on the difference in the input resistance of PG cells versus excitatory neurons at a glomerulus.

Summary Synchronized firing of mitral cells (MCs) in the olfactory bulb (OB) has been hypothesized to help bind information together in olfactory cortex (OC). In this first survey of synchronized firing by suspected MCs in awake-behaving vertebrates we find the surprising result that synchronized firing conveys information on odor value (is it rewarded?) rather than odor identity (what is the odor?). We observed that as mice learned to discriminate between odors synchronous firing responses to the rewarded and unrewarded odors became divergent. Further, adrenergic blockage decreases the magnitude of odor divergence of synchronous trains suggesting that MCs contribute to decision-making through adrenergic-modulated synchronized firing. Thus, in the olfactory system information on stimulus reward is found in MCs one synapse away from the sensory neuron.