Neural firing discharges are often temporally patterned, but it is often ambiguous as to whether the temporal features of these patterns constitute a useful code. Here we show in the mouse olfactory bulb that ensembles of projection neurons respond with complex odor- and concentration-specific dynamic activity sequences developing below and above sniffing frequency. Based on this activity, almost optimal discrimination of presented odors was possible during single sniffs, consistent with reported behavioral data. Within a sniff cycle, slower features of the dynamics alone (>100 ms resolution, including mean firing rate) were sufficient for maximal discrimination. A smaller amount of information was also observed in faster features down to 20-40 ms resolution. Therefore, mitral cell ensemble activity contains information at different timescales that could be separately or complementarily exploited by downstream brain centers to make odor discriminations. Our results also support suggestive analogies in the dynamics of odor representations between insects and mammals.

The ability to group stimuli into perceptual categories is essential for efficient interaction with the environment. Discrete dynamics that emerge in brain networks are believed to be the neuronal correlate of category formation. Observations of such dynamics have recently been made; however, it is still unresolved if they actually match perceptual categories. Using in vivo two-photon calcium imaging in the auditory cortex of mice, we show that local network activity evoked by sounds is constrained to few response modes. Transitions between response modes are characterized by an abrupt switch, indicating attractor-like, discrete dynamics. Moreover, we show that local cortical responses quantitatively predict discrimination performance and spontaneous categorization of sounds in behaving mice. Our results therefore demonstrate that local nonlinear dynamics in the auditory cortex generate spontaneous sound categories which can be selected for behavioral or perceptual decisions.

Discrimination between foods is crucial for the nutrition and survival of animals. Remarkable progress has been made through molecular and genetic manipulations in the understanding of the coding of taste at the receptor level. However, much less is known about the cortical processing of taste sensation and the organizing principles of the gustatory cortex (GC). Using genetic tracing, it has recently been shown that sweet and bitter taste are processed through segregated neuronal circuitries along the gustatory pathway up to the cortical level. This is in disagreement with the evidence that GC neurons recorded in both anesthetized and behaving animals responded to multiple taste modalities (including sweet and bitter). To investigate the functional architecture of the GC in regard to taste modalities, we used in vivo intrinsic optical imaging, a technique that has been successfully applied to explore the organization of other neocortical regions. We found that four of the primary taste modalities (sweet, bitter, salty, and sour) are represented by distinctive spatial patterns but that no region was specific to a single modality. In addition, we found that two tastants of similar hedonic value (pleasant or unpleasant) activated areas with more common regions than two tastants with opposite hedonic value. In summary, we propose that these specific cortical patterns can be used to discriminate among various tastants.

Olfactory perception and behaviors critically depend on the ability to identify an odor across a wide range of concentrations. Here, we use calcium imaging to determine how odor identity is encoded in olfactory cortex. We find that, despite considerable trial-to-trial variability, odor identity can accurately be decoded from ensembles of co-active neurons that are distributed across piriform cortex without any apparent spatial organization. However, piriform response patterns change substantially over a 100-fold change in odor concentration, apparently degrading the population representation of odor identity. We show that this problem can be resolved by decoding odor identity from a subpopulation of concentration-invariant piriform neurons. These concentration-invariant neurons are overrepresented in piriform cortex but not in olfactory bulb mitral and tufted cells. We therefore propose that distinct perceptual features of odors are encoded in independent subnetworks of neurons in the olfactory cortex.DOI: http://dx.doi.org/10.7554/eLife.26337.001

The study of the neural basis of olfaction is important both for understanding the sense of smell and for understanding the mechanisms of neural computation. In the olfactory bulb (OB), the spatial patterning of both sensory inputs and synaptic interactions is crucial for processing odor information, although this patterning alone is not sufficient. Recent studies have suggested that representations of odor may already be distributed and dynamic in the first olfactory relay. The growing evidence demonstrating a functional role for the temporal structure of bulbar neuronal activity supports this assumption. However, the detailed mechanisms underlying this temporal structure have never been thoroughly studied. Our study focused on gamma (40-100 Hz) network oscillations in the mammalian OB, which is a form of temporal patterning in bulbar activity elicited by olfactory stimuli. We used computational modeling combined with electrophysiological recordings to investigate the basic synaptic organization necessary and sufficient to generate sustained gamma rhythms. We found that features of gamma oscillations obtained in vitro were identical to those of a model based on lateral inhibition as the coupling modality (i.e., low irregular firing rate and high oscillation stability). In contrast, they differed substantially from those of a model based on lateral excitatory coupling (i.e., high regular firing rate and instable oscillations). Therefore we could precisely tune the oscillation frequency by changing the kinetics of inhibitory events supporting the lateral inhibition. Moreover, gradually decreasing GABAergic synaptic transmission decreased the degree of relay neuron synchronization in response to sensory inputs, both theoretically and experimentally. Thus we have shown that lateral inhibition provides a mechanism by which the dynamic processing of odor information might be finely tuned within the OB circuit.

In the olfactory bulb (OB), odorants induce oscillations in the ␥ range (20 -80 Hz) that play an important role in the processing of sensory information. Synaptic transmission between dendrites is a major contributor to this processing. Glutamate released from mitral cell dendrites excites the dendrites of granule cells, which in turn mediate GABAergic inhibition back onto mitral cells. Although this reciprocal synapse is thought to be a key element supporting oscillatory activity, the mechanisms by which dendrodendritic inhibition induces and maintains ␥ oscillations remain unknown. Here, we assessed the role of the dendrodendritic inhibition, using mice lacking the GABA A receptor ␣1-subunit, which is specifically expressed in mitral cells but not in granule cells. The spontaneous inhibitory postsynaptic current frequency in these mutants was low and was consistent with the reduction of GABA A receptor clusters detected by immunohistochemistry. The remaining GABA A receptors in mitral cells contained the ␣3-subunit and supported slower decaying currents of unchanged amplitude. Overall, inhibitory-mediated interactions between mitral cells were smaller and slower in mutant than in WT mice, although the strength of sensory afferent inputs remained unchanged. Consequently, both experimental and theoretical approaches revealed slower ␥ oscillations in the OB network of mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are strongly constrained by the precise location, subunit composition and kinetics of GABA A receptors expressed in mitral cells.␣1 knockout ͉ GABAA receptor ͉ olfaction ͉ reciprocal synapses I n the olfactory bulb (OB), ␥ frequency (20-80 Hz) oscillations of local field potentials (LFP) reflect synchronized spike discharges of principal neurons (i.e., mitral/tufted cells), and may be part of the encoding of sensory information (reviewed in refs. 1 and 2). In line with this assumption, the strength of ␥ oscillations correlates with both discrimination abilities (3) and learning capacities (4, 5) in rodents.In vivo experimental approaches revealed that ␥ oscillations are intrinsic to the OB circuitry (5-7) and are even preserved in slice preparations (8, 9), which suggests that intrinsic properties of the OB connectivity are sufficient to give rise to large-scale synchronization. Analysis of the mechanisms involved has focused almost exclusively on the excitatory principal neurons (i.e., mitral cells) and included intrinsic subthreshold oscillations (10, 11) or mutual excitation through electrical coupling and glutamate spillover between mitral cells sharing the same glomerulus (12-14). As a result, relatively little is known about the role of local inhibitory interneurons in generating and maintaining network oscillations, although pioneering studies proposed dendrodendritic inhibition as a key element for inducing fast rhythms (15)(16)(17). This assumption is also supported by the fact that interneurons constitute the main target of excitatory centrifugal fibers (18,19) k...

Sound recognition relies not only on spectral cues, but also on temporal cues, as demonstrated by the profound impact of time reversals on perception of common sounds. To address the coding principles underlying such auditory asymmetries, we recorded a large sample of auditory cortex neurons using two-photon calcium imaging in awake mice, while playing sounds ramping up or down in intensity. We observed clear asymmetries in cortical population responses, including stronger cortical activity for up-ramping sounds, which matches perceptual saliency assessments in mice and previous measures in humans. Analysis of cortical activity patterns revealed that auditory cortex implements a map of spatially clustered neuronal ensembles, detecting specific combinations of spectral and intensity modulation features. Comparing different models, we show that cortical responses result from multi-layered nonlinearities, which, contrary to standard receptive field models of auditory cortex function, build divergent representations of sounds with similar spectral content, but different temporal structure.

Long-lasting changes in synaptic connections induced by relevant experiences are believed to represent the physical correlate of memories. Here, we combined chronic in vivo two-photon imaging of dendritic spines with auditory-cued classical conditioning to test if the formation of a fear memory is associated with structural changes of synapses in the mouse auditory cortex. We find that paired conditioning and unpaired conditioning induce a transient increase in spine formation or spine elimination, respectively. A fraction of spines formed during paired conditioning persists and leaves a long-lasting trace in the network. Memory recall triggered by the reexposure of mice to the sound cue did not lead to changes in spine dynamics. Our findings provide a synaptic mechanism for plasticity in sound responses of auditory cortex neurons induced by auditory-cued fear conditioning; they also show that retrieval of an auditory fear memory does not lead to a recapitulation of structural plasticity in the auditory cortex as observed during initial memory consolidation.learning | auditory fear conditioning | reconsolidation