Odors synchronize the activity of olfactory bulb mitral cells that project to the same glomerulus. In vitro, a slow rhythmic excitation intrinsic to the glomerular network persists, even in the absence of afferent input. We show here that a subpopulation of juxtaglomerular cells, external tufted (ET) cells, may trigger this rhythmic activity. We used paired whole-cell recording and Ca 2ϩ imaging in bulb slices from wild-type and transgenic mice expressing the fluorescent Ca 2ϩ indicator protein GCaMP-2. Slow, periodic population bursts in mitral cells were synchronized with spontaneous discharges in ET cells. Moreover, activation of a single ET cell was sufficient to evoke population bursts in mitral cells within the same glomerulus. Stimulation of the olfactory nerve induced similar population bursts and activated ET cells at a lower threshold than mitral cells, suggesting that ET cells mediate feedforward excitation of mitral cells. We propose that ET cells act as essential drivers of glomerular output to the olfactory cortex.

Olfactory sensory neurons (OSNs) expressing the same odorant receptor converge in specific glomeruli where they transmit olfactory information to mitral cells. Surprisingly, synaptic mechanisms underlying mitral cell activation are still controversial. Using patch-clamp recordings in mouse olfactory bulb slices, we demonstrate that stimulation of OSNs produces a biphasic postsynaptic excitatory response in mitral cells. The response was initiated by a fast and graded monosynaptic input from OSNs and followed by a slower component of feedforward excitation, involving dendro-dendritic interactions between external tufted, tufted and other mitral cells. The mitral cell response occasionally lacked the fast OSN input when few afferent fibers were stimulated. We also show that OSN stimulation triggers a strong and slow feedforward inhibition that shapes the feedforward excitation but leaves unaffected the monosynaptic component. These results confirm the existence of direct OSN to mitral cells synapses but also emphasize the prominence of intraglomerular feedforward pathways in the mitral cell response.

The activity of mitral and tufted cells, the principal neurons of the olfactory bulb, is modulated by several classes of interneurons. Among them, diverse periglomerular (PG) cell types interact with the apical dendrites of mitral and tufted cells inside glomeruli at the first stage of olfactory processing. We used paired recording in olfactory bulb slices and two-photon targeted patch-clamp recording in vivo to characterize the properties and connections of a genetically identified population of PG cells expressing enhanced yellow fluorescent protein (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP ϩ PG cells are axonless and monoglomerular neurons that constitute ϳ30% of all PG cells and include calbindin-expressing neurons. They respond to an olfactory nerve stimulation with a short barrage of excitatory inputs mediated by mitral, tufted, and external tufted cells, and, in turn, they indiscriminately release GABA onto principal neurons. They are activated by even the weakest olfactory nerve input or by the discharge of a single principal neuron in slices and at each respiration cycle in anesthetized mice. They participate in a fast-onset intraglomerular lateral inhibition between principal neurons from the same glomerulus, a circuit that reduces the firing rate and promotes spike timing variability in mitral cells. Recordings in other PG cell subtypes suggest that this pathway predominates in generating glomerular inhibition. Intraglomerular lateral inhibition may play a key role in olfactory processing by reducing the similarity of principal cells discharge in response to the same incoming input.

Inhibitory glycine receptors (GlyRs) are mainly expressed in the spinal cord and in the midbrain, where they control motor and sensory pathways. We describe here a fast potentiation of GlyR by intracellular Ca2+. This phenomenon was observed in rat spinal cord neurons and in transfected human cell lines. Potentiation develops in <100 ms, is proportional to Ca2+ influx, and is characterized by an increase in GlyR apparent affinity for glycine. Phosphorylation and G protein pathways appear not to be involved in the potentiation mechanism. Single-channel recordings in cell-attached and excised patches, as well as whole-cell data suggest the presence of a diffusible cytoplasmic factor that modulates the GlyR channel gating properties. Ca2+-induced potentiation may be important for rapid modulation of glycinergic synapses.

In the olfactory bulb, axons of olfactory sensory neurons (OSNs) expressing the same olfactory receptor converge on specific glomeruli. These afferents form axodendritic synapses with mitral/tufted and periglomerular cell dendrites, whereas the dendrites of mitral/tufted cells and periglomerular interneurons form dendrodendritic synapses. The two types of intraglomerular synapses appear to be spatially isolated in subcompartments delineated by astrocyte processes. Because each astrocyte sends processes into a single glomerulus, we used astrocyte recording as an intraglomerular detector of neuronal activity. In glomerular astrocytes, a single shock in the olfactory nerve layer evoked a prolonged inward current, the major part of which was attributable to a barium-sensitive potassium current. The K

Key pointsr Basal forebrain long-range projections to the olfactory bulb are important for olfactory sensitivity and odour discrimination.r Using optogenetics, it was confirmed that basal forebrain afferents mediate IPSCs on granule and deep short axon cells. It was also shown that they selectively innervate specific subtypes of periglomerular (PG) cells.r Three different subtypes of type 2 PG cells receive GABAergic IPSCs from the basal forebrain but not from other PG cells.r Type 1 PG cells, in contrast, do not receive inputs from the basal forebrain but do receive inhibition from other PG cells.r These results shed new light on the complexity and specificity of glomerular inhibitory circuits, as well as on their modulation by the basal forebrain.Abstract Olfactory bulb circuits are dominated by multiple inhibitory pathways that finely tune the activity of mitral and tufted cells, the principal neurons, and regulate odour discrimination. Granule cells mediate interglomerular lateral inhibition between mitral and tufted cells' lateral dendrites whereas diverse subtypes of periglomerular (PG) cells mediate intraglomerular lateral inhibition between their apical dendrites. Deep short axon cells form broad intrabulbar inhibitory circuits that regulate both populations of interneurons. Little is known about the extrabulbar GABAergic circuits that control the activity of these various interneurons. We examined this question using patch-clamp recordings and optogenetics in olfactory bulb slices from transgenic mice. We showed that axonal projections emanating from diverse basal forebrain GABAergic neurons densely project in all layers of the olfactory bulb. These long-range GABAergic projections provide a prominent synaptic input on granule and short axon cells in deep layers as well as on selective subtypes of PG cells. Specifically, three different subclasses of type 2 PG cells receivé Alvaro Sanz Díez obtained his PhD in 2017 from the University of Strasbourg under the supervision of Dr Didier De Saint Jan. There, he studied the inhibitory networks of the mouse olfactory bulb and their connections to the basal forebrain. He is currently a postdoc in Rudy Behnia's lab at Columbia University in New York, where he studies the visual neural networks implicated in colour processing of Drosophila melanogaster. He is interested in how neural circuits encode sensory information and how this is translated behaviourally.A. Sanz Diez and others J Physiol 597.9 robust and target-specific basal forebrain inputs but have little local interactions with other PG cells. In contrast, type 1 PG cells are not innervated by basal forebrain fibres but do interact with other PG cells. Thus, attention-regulated basal forebrain inputs regulate inhibition in all layers of the olfactory bulb with a previously overlooked synaptic complexity that further defines interneuron subclasses.

Sensory systems often respond to rapid stimuli with high frequency and fidelity, as perhaps best exemplified in the auditory system. Fast synaptic responses are fundamental requirements to achieve this task. The importance of speed is less clear in the olfactory system. Moreover, olfactory bulb output mitral cells respond to a single stimulation of the sensory afferents with unusually long EPSPs, lasting several seconds. We examined the temporal characteristics, developmental regulation, and the mechanism generating these responses in mouse olfactory bulb slices. The slow EPSP appeared at postnatal days 10 -11 and was mediated by metabotropic glutamate receptor 1 (mGluR1) and NMDA receptors. mGluR1 contribution was unexpected because its activation usually requires strong, high-frequency stimulation of inputs. However, dendritic release of glutamate from the intraglomerular network caused spillover-mediated recurrent activation of metabotropic glutamate receptors. We suggest that persistent responses in mitral cells amplify the incoming sensory information and, along with asynchronous inputs, drive odor-evoked slow temporal activity in the bulb.

The glycine receptor (GlyR) mediates fast inhibitory synaptic transmission in the spinal cord and brainstem of vertebrates (Rajendra et al. 1997). This pentameric Cl¦ selective channel is composed of two subunit types: the á subunit (48 kDa), which carries the agonist binding site, and the â subunit (58 kDa), which is linked to the cytoskeletal proteins (Kirsch & Betz, 1995). The á isoforms are able to form functional homomeric channels when expressed in Xenopus oocytes or in mammalian cell lines (Schmieden et al. 1992; Takahashi et al. 1992). Their expression is developmentally regulated (Akagi & Miledi, 1988;B echade et al. 1994) and this determines the functional properties of the GlyR during ontogenesis (Takahashi et al. 1992;Morales et al. 1994). Recently the first non-mammalian GlyR subunit, named áZ1, was cloned from the central nervous system of the adult zebrafish Danio rerio (David-Watine et al. 1999a). Our preliminary electrophysiological studies showed that this subunit forms functional homo-oligomeric receptors with several pharmacological properties different from those reported for mammalian á subunit GlyRs (Schmieden et al. 1992(Schmieden et al. , 1993. A peculiar feature of áZ1 is its ability to be activated by ã_aminobutyric acid (GABA) (Bregestovski et al. 1997;David-Watine et al. 1999a). This property is particularly interesting as both inhibitory neurotransmitters, GABA and glycine, have been found in presynaptic boutons in the goldfish (Triller et al. 1987a) and mammalian (Ottersen et al. 1987(Ottersen et al. , 1988Triller et al. 1987a;Todd & Sullivan, 1990;Bohlhalter et al. 1994) spinal cords, suggesting that they can act as co_transmitters (Todd et al. 1996). Moreover, a recent study by Jonas et al. (1998) has provided compelling evidence that GABA and glycine can be co_released from individual vesicles at interneuron-motoneuron synapses in rat spinal cord. Our previous observations indicate that in cDNA-injected Xenopus oocytes, GABA acts on the áZ1 GlyR as a partial agonist. In transfected human cells, its apparent affinity is nearly 10-fold higher (David-Watine et al. 1999a) and its