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Convergence in the Piriform Cortex
Abstract
How are the responses to distinct chemical features integrated to form an olfactory perceptual object? In this issue of Neuron, Davison and Ehlers show that individual piriform cortex neurons receive convergent input from up to 10% of main olfactory bulb glomeruli and are activated by specific spatial patterns of coactive glomeruli.
... Cortical neurons are expected to be more broadly tuned than sensory cells given the convergent circuit architecture of bulbar inputs to the PC (Apicella et al., 2010;Davison and Ehlers, 2011;Vicente and Mainen, 2011). Our data, which makes use of the same odorants to stimulate both OSNs and cortical projections to the OB indeed supports this expectation. ...
Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Odorant mixtures of increasing complexity evoked progressively denser OSN activity, yet cortical feedback activity was of similar sparsity for all stimuli. Representations of complex mixtures were similar in OSNs but were decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibited a sigmoidal relationship, cortical axonal responses were complex and non-monotonic, which could be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to both local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.
... Previous studies revealed that the PC receives highly converged inputs from distributed glomeruli of the main olfactory bulb (MOB; Vicente and Mainen, 2011), and further synthesizes these odor features into configural odor objects with the help of abundant association fibers within it (Haberly, 2001;Wilson and Sullivan, 2011). Besides olfactory inputs, the PC also receives extensive inputs from the cortical and limbic system (Haberly and Price, 1978;Kowianski et al., 1999;Majak et al., 2004;Illig, 2005). ...
The piriform cortex (PC) is a key brain area involved in both processing and coding of olfactory information. It is implicated in various brain disorders, such as epilepsy, Alzheimer’s disease, and autism. The PC consists of the anterior (APC) and posterior (PPC) parts, which are different anatomically and functionally. However, the direct input networks to specific neuronal populations within the APC and PPC remain poorly understood. Here, we mapped the whole-brain direct inputs to the two major neuronal populations, the excitatory glutamatergic principal neurons and inhibitory γ-aminobutyric acid (GABA)-ergic interneurons within the APC and PPC using the rabies virus (RV)-mediated retrograde trans-synaptic tracing system. We found that for both types of neurons, APC and PPC share some similarities in input networks, with dominant inputs originating from the olfactory region (OLF), followed by the cortical subplate (CTXsp), isocortex, cerebral nuclei (CNU), hippocampal formation (HPF) and interbrain (IB), whereas the midbrain (MB) and hindbrain (HB) were rarely labeled. However, APC and PPC also show distinct features in their input distribution patterns. For both types of neurons, the input proportion from the OLF to the APC was higher than that to the PPC; while the PPC received higher proportions of inputs from the HPF and CNU than the APC did. Overall, our results revealed the direct input networks of both excitatory and inhibitory neuronal populations of different PC subareas, providing a structural basis to analyze the diverse PC functions.
Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Here, we show that odorant mixtures of increasing complexity evoke progressively denser OSN activity, yet cortical feedback activity is of similar sparsity for all stimuli. Also, representations of complex mixtures are similar in OSNs but are decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibit a sigmoidal relationship, cortical axonal responses are complex and nonmonotonic, which can be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.
The Instituto Gulbenkian de Ciência (IGC)
is an international biomedical research
and graduate training Institute,
founded and supported by the
Calouste Gulbenkian Foundation,
in Portugal.
In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.
Pyramidal cells in piriform cortex integrate sensory information from multiple olfactory bulb mitral and tufted (M/T) cells. However, whether M/T cells belonging to different olfactory bulb glomeruli converge onto individual cortical cells is unclear. Here we use calcium imaging in an olfactory bulb-cortex slice preparation to provide direct evidence that neurons in piriform cortex receive convergent synaptic input from different glomeruli. We show that the combined activity of distinct glomerular pathways recruits ensembles of pyramidal cells that are not activated by the individual pathways alone. This cooperative recruitment of cortical neurons only occurs over a narrow time window and is a feature intrinsic to the olfactory cortex that can be explained by the integration of converging, subthreshold synaptic input. Cooperative recruitment enhances the differences between cortical representations of partially overlapping input patterns and may contribute to the initial steps of olfactory discrimination.
The properties of cortical circuits underlying central representations of sensory stimuli are poorly understood. Here we use in vivo cell-attached and whole-cell voltage-clamp recordings to reveal how excitatory and inhibitory synaptic input govern odor representations in rat primary olfactory (piriform) cortex. We show that odors evoke spiking activity that is sparse across the cortical population. We find that unbalanced synaptic excitation and inhibition underlie sparse activity: inhibition is widespread and broadly tuned, while excitation is less common and odor-specific. "Global" inhibition can be explained by local interneurons that receive ubiquitous and nonselective odor-evoked excitation. In the temporal domain, while respiration imposes a slow rhythm to olfactory cortical responses, odors evoke fast (15-30 Hz) oscillations in synaptic activity. Oscillatory excitation precedes inhibition, generating brief time windows for precise and temporally sparse spike output. Together, our results reveal that global inhibition and oscillations are major synaptic mechanisms shaping odor representations in olfactory cortex.
We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes odor quality in the olfactory bulb. Receptor swap experiments suggest that the olfactory receptor plays an instructive role in the guidance process but cannot be the sole determinant in the establishment of this map. This genetic approach may be more broadly applied to visualize the development and plasticity of projections in the mammalian nervous system.
Much data on the olfactory bulb (OB) indicates that structural characteristics of odorant molecules are encoded as ordered, spatially consolidated sets of active cells. New results with "genetic tracing" (Zou et al. [2001] Nature 414:173-179) suggest that spatial order is also present in projections from the OB to the olfactory cortex. For the piriform cortex (PC), results with this technique indicate that afferents conveying input derived from single olfactory receptors (ORs) are distributed to well-defined patches in the anterior PC (APC) but that these patches are much larger than in the OB. We have used c-fos induction to examine how input patterning for single ORs is translated into patterns of odor-evoked cellular activity in the PC. The laminar distribution of labeled cells and dual-immunostaining for gamma-aminobutyric acid (GABA)ergic markers indicated that activity was detected largely in pyramidal cells. In odor-stimulated rats, labeled cells were present throughout the posterior PC (PPC) but were concentrated in prominent rostrocaudal bands in APC. Analysis of responses to different odorants and concentrations revealed that locations and shapes of bands conveyed no apparent information regarding odor quality, rather, they appeared to correspond to subregions of the APC distinguished by cytoarchitecture and connectivity. Small-scale variations in labeling density were observed within APC bands and throughout the PPC that could reflect the presence of a complex topographical order, but discrete patches at consistent locations as observed by genetic tracing were absent. This finding suggests that as a result of afferent overlap and intracortical processing, odor-quality information is represented by spatially distributed sets of cells. A distributed organization may be optimal for discriminating biologically relevant odorants that activate large numbers of ORs.
Despite a remarkably precise spatial representation of odorant stimuli in the early stages of olfactory processing, the projections to the olfactory (piriform) cortex are more diffuse and show characteristics of a combinatorial array, with extensive overlap of afferent inputs and widespread intracortical association connections. Furthermore, although there is increasing evidence for the importance of temporal structure in olfactory bulb odorant-evoked output, little is known about how this temporal patterning is translated within cortical neural ensembles. The present study used multichannel electrode arrays and paired single-unit recordings in rat anterior piriform cortex to test several predictions regarding ensemble coding in this system. The results indicate that odorants evoke activity in a spatially scattered ensemble of anterior piriform cortex neurons, and the ensemble activity includes a rich temporal structure. The most pronounced discrimination between different odorants by cortical ensembles occurs during the first inhalation of a 2 s stimulus. The distributed spatial and temporal structure of cortical activity is present at both global and local scales, with neighboring single units contributing to coding of different odorants and active at different phases of the respiratory cycle. Finally, cross-correlogram analyses suggest that cortical unit activity reflects not only afferent input from the olfactory bulb but also intrinsic activity within the intracortical association fiber system. These results provide direct evidence for predictions stemming from anatomical- and theoretical-based models of piriform cortex.
Synapses are the contact sites that enable neurons to form connections between each other in order to transmit and process neural information. Synaptic organization is concerned with the principles by which neurons form circuits that mediate the specific functional operations of different brain regions. One of the aims of this book is to show that the study of synaptic organization-in its full multidisciplinary, multilevel, and theoretical dimension-is a powerful means of integrating brain information to give clear insights into the neural basis of behavior. This book, which has been revised in this the fifth edition, details local circuits in the different regions of the brain. The results of the mouse and human genome projects are incorporated. Also the book contains support from neuroscience databases. Among the new advances covered are 2-photon confocal laser microscopy of dendrites and dendritic spines, biochemical analyses, and dual patch and multielectrode recordings, applied together with an increasing range of behavioral and gene-targeting methods. © 974, 1979, 1990, 1998, 2004 by Oxford University Press, Inc. All rights reserved.
Odors are initially encoded in the brain as a set of distinct physicochemical characteristics but are ultimately perceived as a unified sensory object--a "smell." It remains unclear how chemical features encoded by diverse odorant receptors and segregated glomeruli in the main olfactory bulb (MOB) are assembled into integrated cortical representations. Combining patterned optical microstimulation of MOB with in vivo electrophysiological recordings in anterior piriform cortex (PCx), we assessed how cortical neurons decode complex activity patterns distributed across MOB glomeruli. PCx firing was insensitive to single-glomerulus photostimulation. Instead, individual cells reported higher-order combinations of coactive glomeruli resembling odor-evoked sensory maps. Intracellular recordings revealed a corresponding circuit architecture providing each cortical neuron with weak synaptic input from a distinct subpopulation of MOB glomeruli. PCx neurons thus detect specific glomerular ensembles, providing an explicit neural representation of chemical feature combinations that are the hallmark of complex odor stimuli.
Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in the nose is converted into a segregated map in the olfactory bulb. Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.
Sensory information may be represented in the brain by stereotyped mapping of axonal inputs or by patterning that varies between individuals. In olfaction, a stereotyped map is evident in the first sensory processing centre, the olfactory bulb (OB), where different odours elicit activity in unique combinatorial patterns of spatially invariant glomeruli. Activation of each glomerulus is relayed to higher cortical processing centres by a set of ∼20-50 'homotypic' mitral and tufted (MT) neurons. In the cortex, target neurons integrate information from multiple glomeruli to detect distinct features of chemically diverse odours. How this is accomplished remains unclear, perhaps because the cortical mapping of glomerular information by individual MT neurons has not been described. Here we use new viral tracing and three-dimensional brain reconstruction methods to compare the cortical projections of defined sets of MT neurons. We show that the gross-scale organization of the OB is preserved in the patterns of axonal projections to one processing centre yet reordered in another, suggesting that distinct coding strategies may operate in different targets. However, at the level of individual neurons neither glomerular order nor stereotypy is preserved in either region. Rather, homotypic MT neurons from the same glomerulus innervate broad regions that differ between individuals. Strikingly, even in the same animal, MT neurons exhibit extensive diversity in wiring; axons of homotypic MT pairs diverge from each other, emit primary branches at distinct locations and 70-90% of branches of homotypic and heterotypic pairs are non-overlapping. This pronounced reorganization of sensory maps in the cortex offers an anatomic substrate for expanded combinatorial integration of information from spatially distinct glomeruli and predicts an unanticipated role for diversification of otherwise similar output neurons.
The stimulus complexity of naturally occurring odours presents unique challenges for central nervous systems that are aiming to internalize the external olfactory landscape. One mechanism by which the brain encodes perceptual representations of behaviourally relevant smells is through the synthesis of different olfactory inputs into a unified perceptual experience--an odour object. Recent evidence indicates that the identification, categorization and discrimination of olfactory stimuli rely on the formation and modulation of odour objects in the piriform cortex. Convergent findings from human and rodent models suggest that distributed piriform ensemble patterns of olfactory qualities and categories are crucial for maintaining the perceptual constancy of ecologically inconstant stimuli.
Olfactory perception is initiated by the recognition of odorants by a large repertoire of receptors in the sensory epithelium. A dispersed pattern of neural activity in the nose is converted into a segregated map in the olfactory bulb. How is this representation transformed at the next processing center for olfactory information, the piriform cortex? Optical imaging of odorant responses in the cortex reveals that the piriform discards spatial segregation as well as chemotopy and returns to a highly distributed organization in which different odorants activate unique but dispersed ensembles of cortical neurons. Neurons in piriform cortex, responsive to a given odorant, are not only distributed without apparent spatial preference but exhibit discontinuous receptive fields. This representation suggests organizational principles that differ from those in neocortical sensory areas where cells responsive to similar stimulus features are clustered and response properties vary smoothly across the cortex.
The projection of the axon and axon collaterals of mitral cells to the olfactory cortex was studied in the rabbit by intracellular staining with horseradish peroxidase (HRP). The stained mitral cell axons were reconstructed from the soma to the most caudal portion of the anterior piriform cortex (aPC). Single mitral cells projected to cytoarchitectonically different areas of the olfactory cortex, i.e., the anterior olfactory nucleus (AON), and the aPC, the olfactory tubercle (OT). All the stained mitrall cells projected to both the AON and the aPC, and about one-fourth of the mitral cells projected to the OT. At the surface of the AON and the aPC, the main axon running in the lateral olfactory tract (LOT) gave off several thin collaterals at various intervals. The collaterals did not project evenly in each area but typically formed patchy terminal arbors which tended to be elongated anteroposteriorly. In both the AON and the aPC, each single mitral cell formed several terminal arbors in layer Ia. The axon collaterals innervating the OT showed two types of projection patterns. One type of collateral was emitted from the main axon within the olfactory bulb, coursed through the ventromedial portion of the olfactory peduncle without joining the main mass of the LOT and terminated mainly in the medial portion of the OT. The other type of collateral emerged from the main axon in the LOT, coursed medioposteriorly, and projected to the lateral portion of the OT.
Although individual mitral cells projected to several parts of the olfactory cortex, the fact that they made dense terminal arbors in specific places in each area suggests that the bulbocortical connections are not diffuse but highly selective.
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