Odor signals are conveyed from the olfactory bulb to the olfactory cortex (OC) by mitral cells (MCs) and tufted cells (TCs). However, whether and how the two types of projection neuron differ in function and axonal connectivity is still poorly understood. Odor responses and axonal projection patterns were compared between MCs and TCs in mice by visualizing axons of electrophysiologically-identified single neurons. TCs demonstrated shorter onset latency for reliable responses than MCs. The shorter latency response of TCs was maintained in a wide range of odor concentrations, whereas MCs responded only to strong signals. Furthermore, individual TCs projected densely to focal targets only in anterior areas of the OC, whereas individual MCs dispersedly projected to all OC areas. Surprisingly, in anterior OC areas, the two cell types projected to segregated sub-areas. These results suggest that MCs and TCs transmit temporally distinct odor information to different OC targets.

2Neural activity was recorded from EC and CA1 of 17 rats trained to solve a simplified version of an odour-place association task thought to depend on interfacing of the hippocampus with inputs from the olfactory bulb and the piriform cortex via the EC 13-15 ( Fig. 1; Supplementary Video 1). On each trial, the animal sampled odours in a cue port for 1 s and then, depending on odour identity, ran to either of two cups for food reward (Fig. 1b). Following 3 weeks of training, the percentage of correct trials increased to asymptotic levels, reaching a criterion of two consecutive sessions of 85% correct performance after 16.8 ± 0.8 days (mean ± s.e.m; Fig. 1c; repeated measures ANOVA: F(20, 320) = 95.6, P < 0.001). Training-days number 2, 6, 10, 14 and 18 were defined as T1-T5, respectively. T5 was post-criterion for all animals.We first examined spectral activity in CA1 of 5 well-trained animals. After these animals had reached the 85% performance criterion, electrodes were implanted across the transverse axis of CA1 ( Fig. 1a; Extended Data Fig. 1a). Analyses focused on activity during the cue-sampling period, when recall of odour-place associations was expected to be initiated ( The observed 20-40 Hz coherence between LEC and CA1 could reflect disynaptic LEC-CA3 and CA3-CA1 coupling 12 . If this were the case, LEC-CA1 coherence would be expressed in both proximal CA1 (pCA1) and dCA1, considering that LEC input terminates indiscriminately along the CA3 transverse axis 13 . However, simultaneous recordings from LEC and pCA1 showed no increase in coherence during the cue interval (3 rats; Fig. 1h). At all frequencies from 13.7 to 33.2 Hz, pCA1-LEC coherence was weaker than dCA1-LEC coherence in the first group of rats (FDR corrected, q < 0.05; 12 tetrode pairs; Fig. 1i). The lack of coupling between LEC and pCA1, and between MEC and dCA1, suggests that the coherence is mediated by direct LEC-CA1 connections.We then asked whether and how oscillatory coupling between LEC and dCA1 evolves as the animals learn to use the odour cues to navigate. Tetrodes were targeted simultaneously to dCA1 and layer III of LEC in 5 rats. Once the electrodes were in place, the rats were trained to To determine whether coupling of 20-40 Hz oscillators in LEC and dCA1 is necessary for successful performance, we assessed activity at T5 on error trials ('T5e'; Supplementary Video 1).Results were compared to an identical number of correct trials from the same session (down-sampled correct trials, 'T5d'). The coherence of LEC and dCA1 oscillations in the 20-40Hz band decreased significantly on error trials ( Fig. 2a-c; paired t-test for all combinations of recording pairs, t(19) = 9.81, P < 0.001; for one pair per animal: t(4) = 5.0, P = 0.007). There was also a decrease in cross-frequency coupling in dCA1 ( Fig. 2f-g; t(9) = 6.30, P < 0.001). These findings suggest that 20-40 Hz coupling of dCA1 and LEC is necessary for successful odour-based navigation.K. M. Igarashi et al. 5The emergence of 20-40 Hz coupling was reflected in individual dCA...

The olfactory bulb (OB) is the first relay station of the central olfactory system in the mammalian brain and contains a few thousand glomeruli on its surface. Because individual glomeruli represent a single odorant receptor, the glomerular sheet of the OB forms odorant receptor maps. This review summarizes the emerging view of the spatial organization of the odorant receptor maps. Recent studies suggest that individual odorant receptors are molecular-feature detecting units, and so are individual glomeruli in the OB. How are the molecular-feature detecting units spatially arranged in the glomerular sheet? To characterize the molecular-feature specificity of an individual glomerulus, it is necessary to determine the molecular receptive range (MRR) of the glomerulus and to compare the molecular structure of odorants within the MRR. Studies of the MRR mapping show that 1) individual glomeruli typically respond to a range of odorants that share a specific combination of molecular features, 2) each glomerulus appears to be unique in its MRR property, and 3) glomeruli with similar MRR properties gather together in proximity and form molecular-feature clusters. The molecular-feature clusters are located at stereotypical positions in the OB and might be part of the neural representation of basic odor quality. Detailed studies suggest that the glomerular sheet represents the characteristic molecular features in a systematic, gradual, and multidimensional fashion. The molecular-feature maps provide a basis for understanding how the olfactory cortex reads the odor maps of the OB.

We asked whether the structural heterogeneity of the hippocampal CA3-CA2 axis is reflected in how space is mapped onto place cells in CA3-CA2. Place fields were smaller and sharper in proximal CA3 than in distal CA3 and CA2. The proximodistal shift was accompanied by a progressive loss in the ability of place cells to distinguish configurations of the same spatial environment, as well as a reduction in the extent to which place cells formed uncorrelated representations for different environments. The transition to similar representations was nonlinear, with the sharpest drop in distal CA3. These functional changes along the CA3-CA2 axis mirror gradients in gene expression and connectivity that partly override cytoarchitectonic boundaries between the subfields of the hippocampus. The results point to the CA3-CA2 axis as a functionally graded system with powerful pattern separation at the proximal end, near the dentate gyrus, and stronger pattern completion at the CA2 end.

In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB) glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC) and olfactory tubercle (OT). We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT). Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.