Odor representations in mammalian cortical circuits

doi:10.1016/j.conb.2010.02.004

Current Opinion in Neurobiology

Volume 20, Issue 3, June 2010, Pages 328-331

https://doi.org/10.1016/j.conb.2010.02.004 Get rights and content

Spatial and temporal activity patterns of olfactory bulb projection neurons underlie the initial representations of odors in the brain. However, olfactory perception ultimately requires the integration of olfactory bulb output in higher cortical brain regions. Recent studies reveal that odor representations are sparse and highly distributed in the rodent primary olfactory (piriform) cortex. Furthermore, odor-evoked inhibition is far more widespread and broadly tuned than excitation in piriform cortex pyramidal cells. Other recent studies highlight how olfactory sensory inputs are integrated within pyramidal cell dendrites and that feedback projections from piriform cortex to olfactory bulb interneurons are a source of synaptic plasticity.

Introduction

Considerable effort has focused on exploring the features of circuits in the neocortex that contribute to visual, auditory, and somatosensory perception. Indeed, studies of sensory regions of neocortex underlying these three modalities have revealed a wealth of fundamental principles. Despite the uniqueness of the stimuli underlying these different sensory modalities, features ranging from the large-scale topographical arrangement of cortical sensory representations to the cellular mechanisms governing stimulus-specific activity often appear remarkably conserved.

In addition to light, sound, and touch the sense of smell plays a vital role in the ability of all animals to experience the external world. Whether it is the scent of a lover or the aroma of our morning coffee, olfactory perception is an important factor in our quality of life. Olfaction is evolutionary primitive and critical for the survival of many animal species — finding food, searching for mates, and avoiding predators are just a few behaviors that rely on odor detection and discrimination.

The molecular logic of the odorant receptors (ORs) expressed by olfactory sensory neurons (OSNs) has provided remarkable insight into the initial steps of odor coding [1]. Recent studies have also revealed how activity from OSNs is transformed into odor representations within the olfactory bulb [2, 3], the first site in the brain that processes olfactory stimuli. However, the mechanisms governing the representation of olfactory information in higher brain regions have been much less explored. This review will highlight recent studies of the primary olfactory (piriform) cortex, a region that plays a critical role in odor discrimination and recognition [4, 5].

Section snippets

Initial odor coding in the brain

In rodents, olfactory information is first processed in the olfactory bulb, where OSNs expressing one of ∼1000 different types of ORs map onto ∼1800 glomeruli [6]. OSNs that express the same receptor converge onto one or two glomeruli and imaging experiments have shown that different odorants elicit distinct spatial patterns of glomerular activity [7, 8, 9]. A recent imaging study of mice and rats revealed great precision across animals (and species) in the spatial layout of glomeruli in

Olfactory input to piriform cortex

Layer 2/3 pyramidal cells, the major principal cells in piriform cortex, receive glutamatergic input from LOT fibers onto their distal apical dendrites in layer 1. In slices of piriform cortex, pyramidal cells are driven to fire spikes by the coincident activation of multiple LOT inputs [16]. Thus, pyramidal cells integrate information from multiple M/T cells and one simple presumption is that individual pyramidal cells pool input from M/T cells belonging to different glomeruli. Consistent with

Odors are represented by distributed cell ensembles in piriform cortex

A natural question is whether the exquisite spatial arrangement of OR input to olfactory bulb glomeruli extends to higher brain regions. Immunohistochemical studies have taken advantage of odor-evoked immediate early gene expression to examine how individual odorants are spatially represented in piriform cortex [20, 21]. Individual odorants induced Fos expression in subsets of pyramidal cells that were sparsely distributed throughout piriform cortex. The distinct, yet partially overlapping

Local inhibitory circuits shape odor representations in piriform cortex

What mechanisms contribute to the sparse odorant-evoked firing of pyramidal cells in piriform cortex? In vivo intracellular voltage-clamp recordings of odorant-evoked excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) provided some clues [23^•]. Across the cortical population, odorant-evoked GABAergic inhibition appeared widespread while excitation was less common. In individual pyramidal cells, excitation was odorant-specific and inhibition was nonselective. Recordings from

Dendritic integration of sensory input in pyramidal cells

The intrinsic properties of pyramidal cell dendrites are also poised to influence the integration of sensory input in piriform cortex. Indeed, the anatomical segregation of LOT inputs onto the distal apical dendrites of pyramidal cells is ideal for studying dendritic integration. Recently, a study combining dual patch-clamp recordings along the soma-apical dendritic axis, calcium imaging, and computational modeling revealed that the properties of pyramidal cell dendrites in piriform cortex

Feedback from piriform cortex to olfactory bulb

In addition to conveying information to a large range of other cortical regions, the axons of pyramidal cells in piriform cortex also make dense projections back to the olfactory bulb [4]. These excitatory feedback connections target olfactory bulb granule cells, the main GABAergic interneurons that govern self and lateral dendrodendritic inhibition of M/T cells [3]. Activation of facilitating glutamatergic inputs from piriform cortex onto the proximal dendritic spines of granule cells has been

Conclusions

Together, these studies indicate some notable differences in how sensory information is represented and processed in the piriform cortex compared to sensory regions of neocortex. Olfactory cortical representations are dispersed and overlapping rather than spatially clustered and there does not appear to be a chemotopic order in piriform cortex. Furthermore, unbalanced synaptic excitation and inhibition underlie firing activity that is sparse across the olfactory cortical population. Unlike the

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest

Acknowledgement

Work in the author's laboratory is supported by NIDCD R01DC04682.

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The human olfactory system has two discrete channels of sensory input, arising from olfactory epithelia housed in the left and right nostrils. Here, we asked whether the primary olfactory cortex (piriform cortex [PC]) encodes odor information arising from the two nostrils as integrated or distinct stimuli. We recorded intracranial electroencephalogram (iEEG) signals directly from PC while human subjects participated in an odor identification task where odors were delivered to the left, right, or both nostrils. We analyzed the time course of odor identity coding using machine-learning approaches and found that uni-nostril odor inputs to the ipsilateral nostril are encoded ∼480-ms faster than odor inputs to the contralateral nostril on average. During naturalistic bi-nostril odor sampling, odor information emerged in two temporally segregated epochs, with the first epoch corresponding to the ipsilateral and the second epoch corresponding to the contralateral odor representations. These findings reveal that PC maintains distinct representations of odor input from each nostril through temporal segregation, highlighting an olfactory coding scheme at the cortical level that can parse odor information across nostrils within the course of a single inhalation.
Adaptive olfactory circuitry restores function despite severe olfactory bulb degeneration
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The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortices in these mice responded to odors, and its neural activity sufficed to decode odor identity. We found that sensory neurons express the full repertoire of olfactory receptors, and their axons project primarily to the rudiments of the OB but also, ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced, and the morphology of their dendrites was abnormal, extending over large regions within the OB. Glomerular organization was totally lost in the severe cases of OB degeneration and altered in the more conserved OBs. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements believed to be essential for olfaction, and it may explain reported retention of olfaction in humans with degenerated OBs.
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Apolipoprotein knockout mice presented impairment in olfaction and showed alterations in GABAergic inhibition in the OB, especially PV+ interneurons [62]. GABAergic inhibitory interneurons including PV-, CB-, and cholecystokinin (CCK) - interneurons [26] mediate the function of OB like neuroplasticity [63,64]. In the OB, PV-expressing interneurons are mainly located in the EPL [43], while CB-expressing interneurons are mainly concentrated in the GL [65].
Overweight induced by high-fat diet (HFD) represents one of the major health concerns in modern societies, which can cause lasting peripheral and central metabolic disorders in all age groups. Specifically, childhood obesity could lead to life-long impact on brain development and functioning. On the other hand, environmental enrichment (EE) has been demonstrated to be beneficial for learning and memory. Here, we explored the impact of high-fat diet on olfaction and organization of olfactory bulb cells in adolescent mice, and the effect of EE intervention thereon. Puberty mice (3-week-old) fed with HFD for 10 weeks exhibited poorer odor sensitivity and olfactory memory relative to controls consuming standard chows. The behavioral deficits were rescued in the HFD group with EE intervention. Neuroanatomically, parvalbumin (PV) interneurons in the olfactory bulb (OB) were reduced in the HFD-fed animals relative to control, while EE intervention also normalized this alteration. In contrast, cells expressing calbindin (CB), doublecortin (DCX) in the OB were not altered. Our findings suggest that PV interneurons may play a crucial role in mediating the HFD-induced olfactory deficit in adolescent mice, and can also serve a protective effect of EE against the functional deficit.
Characterization of odor-evoked neural activity in the olfactory peduncle
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Sensory physiological studies characterizing principles of sensory representation are necessary to provide insight to fully develop theories addressing functional diversity within the olfactory system. Although piriform cortex (PC), the most prominent OB target, has been the main focus for physiological investigation among primary olfactory areas (Isaacson, 2010; Stettler & Axel, 2009; Wilson & Sullivan, 2011), a growing body of research is examining features of sensory coding and functional organization in closely associated olfactory regions, including the olfactory tubercle (OT) (Gadziola et al., 2015; Payton et al., 2012; Rampin et al., 2012; Wesson & Wilson, 2010), entorhinal cortex (EC) (Xu & Wilson, 2012), cortical amygdala (CoA) (Iurilli & Datta, 2017), and the anterior olfactory nucleus (AON) (Kikuta et al., 2008, 2010; Lei et al., 2006; ; Tsuji et al., 2019). Limited data available to date from single-unit electrophysiological studies suggest that, despite cytoarchitectural and organizational differences across olfactory areas, populations of neurons often exhibit response characteristics that resemble those observed in PC (Iurilli & Datta, 2017; Payton et al., 2012).
The tenia tecta is extensively interconnected with the main olfactory bulb and olfactory cortical areas and is well positioned to contribute to olfactory processing. However, little is known about odor representation within its dorsal (DTT) and ventral (VTT) components. To address this need, spontaneous and odor-evoked activity of DTT and VTT neurons was recorded from urethane anesthetized mice and compared to activity recorded from adjacent areas within adjacent caudomedial aspects of the anterior olfactory nucleus (AON). Neurons recorded from DTT, VTT, and AON exhibited odor-selective alterations in firing rate in response to a diverse set of monomolecular odorants. While DTT and AON neurons exhibited similar tuning breadth, selectivity, and response topography, the proportion of odor-selective neurons was substantially higher in the DTT. These findings provide evidence that the tenia tecta may contribute to the encoding of specific stimulus attributes. Further work is needed to fully characterize functional organization of the tenia tecta and its contribution to sensory representation and utilization.
Pentylenetetrazol kindling induces cortical astrocytosis and increased expression of extracellular matrix molecules in mice
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Although epilepsy is one of the most common chronic neurological disorders with a prevalence of approximately 1.0 %, the underlying pathophysiology remains to be elucidated. Understanding the molecular and cellular mechanisms involved in the development of epilepsy is important for the development of appropriate therapeutic strategy. In this study, we investigated the effects of status epilepticus on astrocytes, microglia, and extracellular matrix (ECM) molecules in the somatosensory cortex and piriform cortex of mice. Activation of astrocytes was observed in many cortices except the retrosplenial granular cortex after pentylenetetrazol (PTZ)-induced kindling in mice. Activated astrocytes in the cortex were found in layers 1–3 but not in layers 4–6. In the somatosensory and piriform cortices, no change was observed in the number of parvalbumin (PV)-positive neurons and PV-positive neurons covered with perineuronal nets. However, the amount of ECM in the extracellular space increased. The expression of VGLUT1- and GAD67-positive synapses also increased. Thus, in the PTZ-kindling epilepsy mice model, an increase in the number of ECM molecules and activation of astrocytes were observed in the somatosensory cortex and piriform cortex. These results indicate that PTZ-induced seizures affect not only the hippocampus but also other cortical areas. Our study findings may help to develop new therapeutic approaches to prevent seizures or their sequelae.
Layer-specific expression of extracellular matrix molecules in the mouse somatosensory and piriform cortices
2019, IBRO Reports
In the developing central nervous system (CNS), extracellular matrix (ECM) molecules have regulating roles such as in brain development, neural-circuit maturation, and synaptic-function control. However, excluding the perineuronal net (PNN) area, the distribution, constituent elements, and expression level of granular ECM molecules (diffuse ECM) present in the mature CNS remain unclear. Diffuse ECM molecules in the CNS share the components of PNNs and are likely functional. As cortical functions are greatly region-dependent, we hypothesized that ECM molecules would differ in distribution, expression level, and components in a region- and layer-dependent manner. We examined the layer-specific expression of several chondroitin sulfate proteoglycans (aggrecan, neurocan, and brevican), tenascin-R, Wisteria floribunda agglutinin (WFA)-positive molecules, hyaluronic acid, and link protein in the somatosensory and piriform cortices of mature mice. Furthermore, we investigated expression changes in WFA-positive molecules due to aging. In the somatosensory cortex, PNN density was particularly high at layer 4 (L4), but not all diffuse ECM molecules were highly expressed at L4 compared to the other layers. There was almost no change in tenascin-R and hyaluronic acid in any somatosensory-cortex layer. Neurocan showed high expression in L1 of the somatosensory cortex. In the piriform cortex, many ECM molecules showed higher expression in L1 than in the other layers. However, hyaluronic acid showed high expression in deep layers. Here, we clarified that ECM molecules differ in constituent elements and expression in a region- and layer-dependent manner. Region-specific expression of ECM molecules is possibly related to functions such as region-specific plasticity and vulnerability.

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Odor representations in mammalian cortical circuits

Introduction

Section snippets

Initial odor coding in the brain

Olfactory input to piriform cortex

Odors are represented by distributed cell ensembles in piriform cortex

Local inhibitory circuits shape odor representations in piriform cortex

Dendritic integration of sensory input in pyramidal cells

Feedback from piriform cortex to olfactory bulb

Conclusions

References and recommended reading

Acknowledgement

Cell

Curr Opin Neurobiol

Semin Cell Dev Biol

Cell

Neuron

Neuron

J Physiol

Nat Neurosci

J Neurosci

Proc Natl Acad Sci U S A

Nat Rev Neurosci

J Neurophysiol

Cereb Cortex

Early events in olfactory processing

Annu Rev Neurosci

Odor maps in the mammalian olfactory bulb: domain organization and odorant structural features

Nat Neurosci

Precision and diversity in an odor map on the olfactory bulb

Nat Neurosci

Dynamic ensemble odor coding in the mammalian olfactory bulb: sensory information at different timescales

Neuron

Sparse odor coding in awake behaving mice

J Neurosci

Spatio-temporal dynamics of odor representations in the mammalian olfactory bulb

Neuron