Synaptic transmission between dendrites in the olfactory bulb is thought to play a major role in the processing of olfactory information. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic dendrodendritic inhibition back onto mitral dendrites. We examined the mechanisms governing reciprocal dendritic transmission in rat olfactory bulb slices. We find that NMDA receptors play a critical role in this dendrodendritic inhibition. As with axonic synapses, the dendritic release of fast neurotransmitters relies on N- and P/Q-type calcium channels. The magnitude of dendrodendritic transmission is directly proportional to dendritic calcium influx. Furthermore, recordings from pairs of mitral cells show that dendrodendritic synapses can mediate lateral inhibition independently of axonal action potentials.

Inhibition generated by granule cells, the most common GABAergic cell type in the olfactory bulb, plays a critical role in shaping the output of the olfactory bulb. However, relatively little is known about the synaptic mechanisms responsible for activating these interneurons in addition to the specialized dendrodendritic synapses located on distal dendrites. Using two-photon guided minimal stimulation in acute rat brain slices, we found that distal and proximal excitatory synapses onto granule cells are functionally distinct. Proximal synapses arise from piriform cortical neurons and facilitate with paired-pulse stimulation, whereas distal dendrodendritic synapses generate EPSCs with slower kinetics that depress with paired stimulation. Proximal cortical feedback inputs can relieve the tonic Mg block of NMDA receptors (NMDARs) at distal synapses and gate dendrodendritic inhibition onto mitral cells. Most excitatory synapses we examined onto granule cells activated both NMDARs and AMPA receptors, whereas a subpopulation appeared to be NMDAR silent. The convergence of two types of excitatory inputs onto GABAergic granule cells provides a novel mechanism for regulating the degree of interglomerular processing of sensory input in the olfactory bulb through piriform cortex/olfactory bulb synaptic interactions.

Mitral cells, the principal cells of the olfactory bulb, respond to sensory stimulation with precisely timed patterns of action potentials. By contrast, the same neurons generate intermittent spike clusters with variable timing in response to simple step depolarizations. We made whole cell recordings from mitral cells in rat olfactory bulb slices to examine the mechanisms by which normal sensory stimuli could generate precisely timed spike clusters. We found that individual mitral cells fired clusters of action potentials at 20-40 Hz, interspersed with periods of subthreshold membrane potential oscillations in response to depolarizing current steps. TTX (1 μM) blocked a sustained depolarizing current and fast subthreshold oscillations in mitral cells. Phasic stimuli that mimic trains of slow excitatory postsynaptic potentials (EPSPs) that occur during sniffing evoked precisely timed spike clusters in repeated trials. The amplitude of the first simulated EPSP in a train gated the generation of spikes on subsequent EPSPs. 4-aminopyridine (4-AP)–sensitive K+ channels are critical to the generation of spike clusters and reproducible spike timing in response to phasic stimuli. Based on these results, we propose that spike clustering is a process that depends on the interaction between a 4-AP–sensitive K+ current and a subthreshold TTX-sensitive Na+ current; interactions between these currents may allow mitral cells to respond selectively to stimuli in the theta frequency range. These intrinsic properties of mitral cells may be important for precisely timing spikes evoked by phasic stimuli that occur in response to odor presentation in vivo.

The olfactory bulb is a second-order brain region that connects sensory neurons with cortical areas. However, the olfactory bulb does not appear to play a simple relay role and is subject instead to extensive local and extrinsic synaptic influences. Prime among the external, or centrifugal, inputs is the dense cholinergic innervation from the basal forebrain, which terminates in both the granule cell and plexiform layers. Cholinergic inputs to the bulb have been implicated in olfactory working memory tasks in rodents and may be related to olfactory deficits reported in people with neurodegenerative disorders that involve basal forebrain neurons. In this study, we use whole-cell recordings from acute rat slices to demonstrate that one function of this input is to potentiate the excitability of GABAergic granule cells and thereby modulate inhibitory drive onto mitral cells. This increase in granule cell excitability is mediated by a concomitant decrease in the normal afterhyperpolarization response and augmentation of an afterdepolarization, both triggered by pirenzepine-sensitive M 1 receptors. The afterdepolarization was dependent on elevations in intracellular calcium and appeared to be mediated by a calciumactivated nonselective cation current (I CAN ). Near firing threshold, depolarizing inputs could evoke quasipersistent firing characterized by irregular discharges that lasted, on average, for 2 min. In addition to regulating the excitability of the primary interneuronal subtype in the bulb, M 1 receptors regulate the degree of adaptation that occurs during repetitive sniffing-like inputs and may therefore play a critical role in regulating short-term plasticity in the olfactory system.

The dentate hilus has been extensively studied in relation to its potential role in memory and in temporal lobe epilepsy. Little is known, however, about the synapses formed between the two major cell types in this region, glutamatergic mossy cells and hilar interneurons, or the organization of local circuits involving these cells. Using triple and quadruple simultaneous intracellular recordings in rat hippocampal slices, we find that mossy cells evoke EPSPs with high failure rates onto hilar neurons. Mossy cells show profound synapse specificity; 87.5% of their intralamellar connections are onto hilar interneurons. Hilar interneurons also show synapse specificity and preferentially inhibit mossy cells; 81% of inhibitory hilar synapses are onto mossy cells. Hilar IPSPs have low failure rates, are blocked by the GABAA receptor antagonist gabazine, and exhibit short-term depression when tested at 17 Hz. Surprisingly, more than half (57%) of the mossy cell synapses we found onto interneurons were part of reciprocal excitatory/inhibitory local circuit motifs. Neither the high degree of target cell specificity, nor the significant enrichment of structured polysynaptic local circuit motifs, could be explained by nonrandom sampling or somatic proximity. Intralamellar hilar synapses appear to function primarily by integrating synchronous inputs and presynaptic burst discharges, allowing hilar cells to respond over a large dynamic range of input strengths. The reciprocal mossy cell/interneuron local circuit motifs we find enriched in the hilus may generate sparse neural representations involved in hippocampal memory operations.