The Wiring Logic of an Identified Serotonergic Neuron That Spans Sensory Networks.

Serotonergic neurons project widely throughout the brain to modulate diverse physiological and behavioral processes. However, a single-cell resolution understanding of the connectivity of serotonergic neurons is currently lacking. Using a whole-brain EM dataset of a female Drosophila, we comprehensively determine the wiring logic of a broadly projecting serotonergic neuron (the CSDn) that spans several olfactory regions. Within the antennal lobe, the CSDn differentially innervates each glomerulus, yet surprisingly, this variability reflects a diverse set of presynaptic partners, rather than glomerulus-specific differences in synaptic output, which is predominately to local interneurons. Moreover, the CSDn has distinct connectivity relationships with specific local interneuron subtypes, suggesting that the CSDn influences distinct aspects of local network processing. Across olfactory regions, the CSDn has different patterns of connectivity, even having different connectivity with individual projection neurons that also span these regions. Whereas the CSDn targets inhibitory local neurons in the antennal lobe, the CSDn has more distributed connectivity in the LH, preferentially synapsing with principal neuron types based on transmitter content. Last, we identify individual novel synaptic partners associated with other sensory domains that provide strong, top-down input to the CSDn. Together, our study reveals the complex connectivity of serotonergic neurons, which combine the integration of local and extrinsic synaptic input in a nuanced, region-specific manner.SIGNIFICANCE STATEMENT All sensory systems receive serotonergic modulatory input. However, a comprehensive understanding of the synaptic connectivity of individual serotonergic neurons is lacking. In this study, we use a whole-brain EM microscopy dataset to comprehensively determine the wiring logic of a broadly projecting serotonergic neuron in the olfactory system of Drosophila Collectively, our study demonstrates, at a single-cell level, the complex connectivity of serotonergic neurons within their target networks, identifies specific cell classes heavily targeted for serotonergic modulation in the olfactory system, and reveals novel extrinsic neurons that provide strong input to this serotonergic system outside of the context of olfaction. Elucidating the connectivity logic of individual modulatory neurons provides a ground plan for the seemingly heterogeneous effects of modulatory systems.

Gross morphology, histology, and ultrastructure of the olfactory rosette of a critically endangered indicator species, the Delta Smelt, Hypomesus transpacificus.

The Delta Smelt (Hypomesus transpacificus) is a small, semi-anadromous fish native to the San Francisco Bay-Delta Estuary and has been declared as critically endangered. Their olfactory biology, in particular, is poorly understood and a basic description of their sensory anatomy is needed to advance our understanding of the sensory ecology of species to inform conservation efforts to manage and protect them. We provide a description of the gross morphology, histological, immunohistochemical, and ultrastructural features of the olfactory rosette in this fish and discuss some of the functional implications in relation to olfactory ability. We show that Delta Smelt have a multilamellar olfactory rosette with allometric growth. Calretinin immunohistochemistry revealed a diffuse distribution of olfactory receptor neurons within the epithelium. Ciliated, microvillous and crypt neurons were clearly identified using morphological and immunohistochemical features. The olfactory neurons were supported by robust ciliated and secretory sustentacular cells. Although the sense of smell has been overlooked in Delta Smelt, we conclude that the olfactory epithelium has many characteristics of macrosmatic fish. With this study, we provide a foundation for future research into the sensory ecology of this imperiled fish.

Morphogenesis of Olfactory Organ of Bushymouth Catfish Ancistrus dolichopterus (Teleostei: Loricariidae) before Switching to Exogenous Feeding.

Olfaction plays an important role in a fish's life. Its value may differ at different developmental stages, depending on the feeding style of the species. The goal of the present study was to investigate the olfactory organ of a species that feeds mainly on algae- the bushymouth catfish, Ancistrus dolichopterus-at developmental stages from olfactory placode to the definitive olfactory chamber. For this study, we used light and electron (scanning) microscopy. The topography of the olfactory placode of A. dolichopterus is typical for teleostei. Formation of olfactory pit takes place at the same time as rostral elevation formation. Rostral elevation participates in the formation of the nasal bridge and anterior tubular nostril. It was found out that the anlage of olfactory rosette in A. dolichopterus arises earlier than in most teleostei. However, the number of lamellae does not increase until switching to exogenous feeding. We suppose that the early development of olfactory organ is necessary for intraspecific communication, not just for finding food.

Convergence of Olfactory Inputs within the Central Nervous System of a Cartilaginous and a Bony Fish: An Anatomical Indicator of Olfactory Sensitivity.

The volume of the olfactory bulbs (OBs) relative to the brain has been used previously as a proxy for olfactory capabilities in many vertebrate taxa, including fishes. Although this gross approach has predictive power, a more accurate assessment of the number of afferent olfactory inputs and the convergence of this information at the level of the telencephalon is critical to our understanding of the role of olfaction in the behaviour of fishes. In this study, we used transmission electron microscopy to assess the number of first-order axons within the olfactory nerve (ON) and the number of second-order axons in the olfactory peduncle (OP) in established model species within cartilaginous (brownbanded bamboo shark, Chiloscyllium punctatum [CP]) and bony (common goldfish, Carassius auratus [CA]) fishes. The total number of axons varied from a mean of 18.12 ± 7.50 million in the ON to a mean of 0.38 ± 0.21 million in the OP of CP, versus 0.48 ± 0.16 million in the ON and 0.09 ± 0.02 million in the OP of CA. This resulted in a convergence ratio of approximately 50:1 and 5:1, respectively, for these two species. Based on astroglial ensheathing, axon type (unmyelinated [UM] and myelinated [M]) and axon size, we found no differentiated tracts in the OP of CP, whereas a lateral and a medial tract (both of which could be subdivided into two bundles or areas) were identified for CA, as previously described. Linear regression analyses revealed significant differences not only in axon density between species and locations (nerves and peduncles), but also in axon type and axon diameter (p < 0.05). However, UM axon diameter was larger in the OPs than in the nerve in both species (p = 0.005), with no significant differences in UM axon diameter in the ON (p = 0.06) between species. This study provides an in-depth analysis of the neuroanatomical organisation of the ascending olfactory pathway in two fish taxa and a quantitative anatomical comparison of the summation of olfactory information. Our results support the assertion that relative OB volume is a good indicator of the level of olfactory input and thereby a proxy for olfactory capabilities.

Synapse loss in olfactory local interneurons modifies perception.

Synapse loss correlates with cognitive decline in aging and most neurological pathologies. Sensory perception changes often represent subtle dysfunctions that precede the onset of a neurodegenerative disease. However, a cause-effect relationship between synapse loss and sensory perception deficits is difficult to prove and quantify due to functional and structural adaptation of neural systems. Here we modified a PI3K/AKT/GSK3 signaling pathway to reduce the number of synapses--without affecting the number of cells--in five subsets of local interneurons of the Drosophila olfactory glomeruli and measured the behavioral effects on olfactory perception. The neuron subsets were chosen under the criteria of GABA or ChAT expression. The reduction of one subset of synapses, mostly inhibitory, converted the responses to all odorants and concentrations tested as repulsive, while the reduction of another subset, mostly excitatory, led to a shift toward attraction. However, the simultaneous reduction of both synapse subsets restored normal perception. One group of local interneurons proved unaffected by the induced synapse loss in the perception of some odorants, indicating a functional specialization of these cells. Using genetic tools for space and temporal control of synapse number decrease, we show that the perception effects are specific to the local interneurons, rather than the mushroom bodies, and are not based on major structural changes elicited during development. These findings demonstrate that synapse loss cause sensory perception changes and suggest that normal perception is based on a balance between excitation and inhibition.

Working range of stimulus flux transduction determines dendrite size and relative number of pheromone component receptor neurons in moths.

We are proposing that the "relative" abundances of the differently tuned pheromone-component-responsive olfactory receptor neurons (ORNs) on insect antennae are not a result of natural selection working to maximize absolute sensitivity to individual pheromone components. Rather, relative abundances are a result of specifically tuned sensillum-plus-ORN units having been selected to accurately transduce and report to the antennal lobe the maximal ranges of molecular flux imparted by each pheromone component in every plume strand. To not reach saturating stimulus flux levels from the most concentrated plume strands of a pheromone blend, the dendritic surface area of the ORN type that is tuned to the most abundant component of a pheromone blend is increased in dendritic diameter in order to express a greater number of major pheromone component-specific odorant receptors. The increased ability of these enlarged dendrite, major component-tuned ORNs to accurately report very high flux of its component results in a larger working range of stimulus flux able to be accurately transduced by that type of ORN. However, the larger dendrite size and possibly other high-flux adjustments in titers of pheromone-binding proteins and degrading enzymes cause a decrease in absolute sensitivity to lower flux levels of the major component in lower concentration strands of the pheromone blend. In order to restore the ability of the whole-antenna major pheromone component-specific channel to accurately report to its glomerulus the abundance of the major component in lower concentration strands, the number of major component ORNs over the entire antenna is adjusted upward, creating a greater proportion of major component-tuned ORNs than those tuned to minor components. Pheromone blend balance reported by the whole-antennal major and minor component channels in low plume-flux strands is now restored, and the relative fluxes of the 2 components occurring in both low- and high-flux strands are thereby accurately reported to the component-specific glomeruli. Thus, we suggest that the 2 phenomena, dendrite size and relative numbers of differentially tuned ORNs are linked, and both are related to wide disparities in molecular flux ranges occurring for the more abundant and less abundant components in the pheromone blend plume strands.

More than one way to smell ashore - Evolution of the olfactory pathway in terrestrial malacostracan crustaceans.

Crustaceans provide a fascinating opportunity for studying adaptations to a terrestrial lifestyle because within this group, the conquest of land has occurred at least ten times convergently. The evolutionary transition from water to land demands various morphological and physiological adaptations of tissues and organs including the sensory and nervous system. In this review, we aim to compare the brain architecture between selected terrestrial and closely related marine representatives of the crustacean taxa Amphipoda, Isopoda, Brachyura, and Anomala with an emphasis on the elements of the olfactory pathway including receptor molecules. Our comparison of neuroanatomical structures between terrestrial members and their close aquatic relatives suggests that during the convergent evolution of terrestrial life-styles, the elements of the olfactory pathway were subject to different morphological transformations. In terrestrial anomalans (Coenobitidae), the elements of the primary olfactory pathway (antennules and olfactory lobes) are in general considerably enlarged whereas they are smaller in terrestrial brachyurans compared to their aquatic relatives. Studies on the repertoire of receptor molecules in Coenobitidae do not point to specific terrestrial adaptations but suggest that perireceptor events - processes in the receptor environment before the stimuli bind - may play an important role for aerial olfaction in this group. In terrestrial members of amphipods (Amphipoda: Talitridae) as well as of isopods (Isopoda: Oniscidea), however, the antennules and olfactory sensilla (aesthetascs) are largely reduced and miniaturized. Consequently, their primary olfactory processing centers are suggested to have been lost during the evolution of a life on land. Nevertheless, in terrestrial Peracarida, the (second) antennae as well as their associated tritocerebral processing structures are presumed to compensate for this loss or rather considerable reduction of the (deutocerebral) primary olfactory pathway. We conclude that after the evolutionary transition from water to land, it is not trivial for arthropods to establish aerial olfaction. If we consider insects as an ingroup of Crustacea, then the Coenobitidae and Insecta may be seen as the most successful crustacean representatives in this respect.

Structural basis for noradrenergic regulation of neural circuits in the mouse olfactory bulb.

Olfactory input is processed in the glomerulus of the main olfactory bulb (OB) and relayed to higher centers in the brain by projection neurons. Conversely, centrifugal inputs from other brain regions project to the OB. We have previously analyzed centrifugal inputs into the OB from several brain regions using single-neuron labeling. In this study, we analyzed the centrifugal noradrenergic (NA) fibers derived from the locus coeruleus (LC), because their projection pathways and synaptic connections in the OB have not been clarified in detail. We analyzed the NA centrifugal projections by single-neuron labeling and immunoelectron microscopy. Individual NA neurons labeled by viral infection were three-dimensionally traced using Neurolucida software to visualize the projection pathway from the LC to the OB. Also, centrifugal NA fibers were visualized using an antibody for noradrenaline transporter (NET). NET immunoreactive (-ir) fibers contained many varicosities and synaptic vesicles. Furthermore, electron tomography demonstrated that NET-ir fibers formed asymmetrical synapses of varied morphology. Although these synapses were present at varicosities, the density of synapses was relatively low throughout the OB. The maximal density of synapses was found in the external plexiform layer; about 17% of all observed varicosities contained synapses. These results strongly suggest that NA-containing fibers in the OB release NA from both varicosities and synapses to influence the activities of OB neurons. The present study provides a morphological basis for olfactory modulation by centrifugal NA fibers derived from the LC.

Neuronal architecture of the second-order CO2 pathway in the brain of a noctuid moth.

Many insects possess the ability to detect fine fluctuations in the environmental CO2 concentration. In herbivorous species, plant-emitted CO2, in combination with other sensory cues, affect many behaviors including foraging and oviposition. In contrast to the comprehensive knowledge obtained on the insect olfactory pathway in recent years, we still know little about the central CO2 system. By utilizing intracellular labeling and mass staining, we report the neuroanatomy of projection neurons connected with the CO2 sensitive antennal-lobe glomerulus, the labial pit organ glomerulus (LPOG), in the noctuid moth, Helicoverpa armigera. We identified 15 individual LPOG projection neurons passing along different tracts. Most of these uniglomerular neurons terminated in the lateral horn, a previously well-described target area of plant-odor projection neurons originating from the numerous ordinary antennal-lobe glomeruli. The other higher-order processing area for odor information, the calyces, on the other hand, was weakly innervated by the LPOG neurons. The overlapping LPOG terminals in the lateral horn, which is considered important for innate behavior in insects, suggests the biological importance of integrating the CO2 input with plant odor information while the weak innervation of the calyces indicates the insignificance of this ubiquitous cue for learning mechanisms.

Distinct deep short-axon cell subtypes of the main olfactory bulb provide novel intrabulbar and extrabulbar GABAergic connections.

A universal feature of neuronal microcircuits is the presence of GABAergic interneurons that control the activity of glutamatergic principal cells and each other. In the rat main olfactory bulb (MOB), GABAergic granule and periglomerular cells innervate mitral and tufted cells, but the source of their own inhibition remains elusive. Here, we used a combined electrophysiological and morphological approach to investigate a rather mysterious cell population of the MOB. Deep short-axon cells (dSACs) of the inframitral layers are GABAergic and have extensive and characteristic axonal ramifications in various layers of the bulb, based on which unsupervised cluster analysis revealed three distinct subtypes. Each dSAC subtype exhibits different electrical properties but receives similar GABAergic and glutamatergic inputs. The local axon terminals of all dSAC subtypes selectively innervate GABAergic granule and periglomerular cells and evoke GABA(A) receptor-mediated IPSCs. One subpopulation of dSACs (GL-dSACs) creates a novel intrabulbar projection from deep to superficial layers. Another subpopulation (GCL-dSACs) is labeled by retrogradely transported fluorescent microspheres injected into higher olfactory areas, constituting a novel projection-cell population of the MOB. Our results reveal multiple dSAC subtypes, each specialized to influence MOB activity by selectively innervating GABAergic interneurons, and provide direct evidence for novel intrabulbar and extrabulbar GABAergic projections.

Gamma-aminobutyric acid immunostaining in the antennal lobe of the moth Heliothis virescens and its colocalization with neuropeptides.

The antennal lobe is the primary processing center for olfactory information in insects. To understand further the neural circuitry of this brain area, we have investigated the distribution of gamma-aminobutyric acid (GABA) and its colocalization with neuropeptides in the antennal lobe of the noctuid moth Heliothis virescens. Immunocytochemical experiments with an antiserum against GABA showed a large number of labeled somata in the antennal lobe; these somata were located exclusively in the lateral cell cluster. Stained neurites innervating all antennal-lobe glomeruli, including the male-specific macroglomerular complex, suggested a prominent role of GABA in processing olfactory information, including signals from pheromones, interspecifically acting odors, and plant odors. Fibers in two antennocerebral tracts (the middle and dorsal antennocerebral tract) exhibited prominent GABA immunoreactivity. Double-labeling experiments revealed that immunostaining for three neuropeptides, viz., A-type allatostatin, Manduca sexta allatotropin, and FMRFamide-related peptides, was largely colocalized with GABA in cell bodies of the lateral cell cluster. The general absence of peptide immunostaining in the antennocerebral tracts strongly indicated that these peptides were colocalized with GABA in local interneurons of the antennal lobe. In contrast, tachykinin-related peptides occurred in a distinct population of local antennal-lobe neurons that did not exhibit GABA immunostaining. Thus, local interneurons that were not GABAergic were present in the moth antennal lobe.

Vomeronasal neurons promote synaptic formation on dendritic spines but not dendritic shafts in primary culture of accessory olfactory bulb neurons.

To investigate the morphological changes of accessory olfactory bulb (AOB) neurons arising from pheromonal signals, a coculture system of AOB neurons and vomeronasal (VN) neurons had been established. Our previous study indicates that under coculture condition, the density of dendritic spines of an AOB neuron is less and the individual spine-head volume is larger than those under monoculture condition. In this study, to determine whether these differences in the dendrites of AOB neurons reflect the differences in synapse formation and synaptic properties, we observed these cultured cells by electron microscopy. Various synapses were observed under each culture condition. Synapses were classified on the basis of their postsynaptic structure and the size of postsynaptic density (PSD) was measured. Under the coculture condition with VN neurons, synapses on dendritic spines, which formed between AOB neurons, were observed frequently. In contrast, many synapses were formed on dendritic shafts under monoculture condition. The PSD of asymmetrical synapses on the spines under coculture condition was larger than that under monoculture condition. Moreover, some dendrodendritic reciprocal synapses were found only in coculture. We confirmed synapse formation between VN axons and AOB dendrites by immunohistochemical electron microscopy; thus, the characteristics of synapses between AOB neurons are considered to be modified by the synaptic contacts with VN axons.

Early ontogeny of the olfactory organ in a basal actinopterygian fish: polypterus.

The present study employed light and electron microscopic methods to investigate the ontogenetic origin of the olfactory organ in bichirs (Cladistia: Polypteridae) and explore its evolution among osteichthyans. In former studies we demonstrated that in teleosts a subepidermal layer gives rise to the olfactory placode which in turn builds all types of olfactory cells (basal, receptor, supporting, ciliated non-sensory cells). In contrast, the olfactory placodes in sturgeons (Chondrostei: Acipenseridae) as well as in the clawed frog Xenopus laevis (Anura: Pipidae) originate from two different layers. Receptor neurons derive from cells of the subepidermal (sensory) layer and supporting cells from epidermal cells. As sturgeons and amphibians in some characters show a more primitive condition than teleosts, we extended our study to Polypterus to allow for an approach at the basic osteichthyan pattern. In Polypterus, an internal lumen occurs in early ontogenetic stages surrounded by the epithelium of the olfactory placode. Two different populations of supporting cells follow one another: a primary population derives from the subepidermal layer. Later supporting cells develop from epidermal cells by transdifferentiation. The primary opening of the internal lumen to the exterior develops by invagination from the epidermal surface and simultaneously by a counter-directed process of cell dissociation and fragmentation inside the olfactory placode. Our results indicate the following features to be plesiomorphic actinopterygian character states: The primary olfactory pit (prospective olfactory cavity) is formed by invagination of the epidermal and the subepidermal layer (as in Acipenser and Xenopus). The incurrent and excurrent nostrils derive from a single primary opening which elongates and is then separated by an epidermal bridge into the two external openings (as in Acipenser and many teleosts). The olfactory epithelium derives from an epidermal and a subepidermal layer (as in Acipenser and Xenopus). Apomorphic (derived actinopterygian) features are: (1) an internal lumen as primordium of the future olfactory chamber; (2) a subepidermal layer gives rise to the olfactory epithelium and its constituents (Polypterus and teleosts). As to the origin of the olfactory supporting cells in Polypterus we assume a combination of plesiomorphic and apomorphic characters. We conclude that Acipenser and Xenopus exhibit the most widely distributed features among basal osteognathostomes and thus ancestral character states in the development of the olfactory organs.

Inter-axonal recognition organizes Drosophila olfactory map formation.

Olfactory systems across the animal kingdom show astonishing similarities in their morphological and functional organization. In mouse and Drosophila, olfactory sensory neurons are characterized by the selective expression of a single odorant receptor (OR) type and by the OR class-specific connection in the olfactory brain center. Monospecific OR expression in mouse provides each sensory neuron with a unique recognition identity underlying class-specific axon sorting into synaptic glomeruli. Here we show that in Drosophila, although OR genes are not involved in sensory neuron connectivity, afferent sorting via OR class-specific recognition defines a central mechanism of odortopic map formation. Sensory neurons mutant for the Ig-domain receptor Dscam converge into ectopic glomeruli with single OR class identity independent of their target cells. Mosaic analysis showed that Dscam prevents premature recognition among sensory axons of the same OR class. Single Dscam isoform expression in projecting axons revealed the importance of Dscam diversity for spatially restricted glomerular convergence. These data support a model in which the precise temporal-spatial regulation of Dscam activity controls class-specific axon sorting thereby indicating convergent evolution of olfactory map formation via self-patterning of sensory neurons.

An early critical period for long-term plasticity and structural modification of sensory synapses in olfactory cortex.

Critical periods for plasticity of thalamic sensory inputs play an important role in developing neocortical circuits. During an early postnatal time window, pyramidal cells of visual, auditory, and somatosensory cortex undergo structural refinement and possess an enhanced ability for activity-dependent synaptic plasticity. In olfactory cortex, however, pyramidal cells receive direct sensory input from the olfactory bulb, and it is unclear whether the development of olfactory sensory circuits is governed by a critical period. Here, we show that NMDA receptor-dependent long-term potentiation and dendritic spine maturation occur only during a brief postnatal time window at sensory synapses of olfactory cortex pyramidal cells. In contrast, associational synapses onto the same cells retain the capacity for plasticity into adulthood.

Synaptic integration of adult-generated olfactory bulb granule cells: basal axodendritic centrifugal input precedes apical dendrodendritic local circuits.

The adult mammalian olfactory bulb (OB) receives a continuing influx of new interneurons. Neuroblasts from the subventricular zone (SVZ) migrate into the OB and differentiate into granule cells and periglomerular cells that are presumed to integrate into the synaptic circuits of the OB. We have used retroviral infection into the SVZ of mice to label adult-generated granule cells and follow their differentiation and integration into OB circuitry. Using synaptic markers and electron microscopy, we show new granule cells integrating into the reciprocal circuitry of the external plexiform layer (EPL), beginning at 21 d postinfection (dpi). We further show that synapses are formed earlier, beginning at 10 dpi, on the somata and basal dendrites of new cells in the granule cell layer (GCL), before dendritic elaboration in the EPL. In the EPL, elaborate dendritic arbors with spines are first evident at 14 dpi. The density of spines increases from 14 to 28 dpi, and then decreases by 56 dpi. Despite the initial appearance of dendritic spines at 14 dpi in the EPL, no expression of presynaptic or postsynaptic markers is seen until 21 dpi. These data suggest that adult-generated granule cells are first innervated by centrifugal or mitral/tufted cell axon collaterals in the GCL and that these inputs may contribute to their differentiation, maturation, and synaptic integration into the dendrodendritic local circuits found in the EPL.

Distribution of calretinin during development of the olfactory system in the brown trout, Salmo trutta fario: Comparison with other immunohistochemical markers.

Immunocytochemical techniques were used to investigate the appearance and distribution of calretinin in the olfactory system of developing and adult brown trout (Salmo trutta fario L.). The earliest calretinin-immunoreactive (CR-ir) cells were detected in the olfactory placode of 5-mm embryos. In 8-mm embryos, a CR-ir olfactory nerve was observed. The number of CR-ir olfactory receptor cells increased rapidly, and in fry and adults they were characterized by light and electron microscopy as pertaining to three morphological types of receptor cell, called microvillous, ciliated and rod-like cells or crypt cells. Comparisons of the cells labeled with CR and with more general olfactory markers (acetylated tubulin and keyhole limpet haemocyanin) in alevins and fry revealed that CR-ir cells represent only a subpopulation of olfactory receptor cells. Large cells located in the primordial mitral cell layer were the first CR-ir neuronal population of the olfactory bulbs and were observed in 7-mm embryos. These cells express high HuC/D immunoreactivity and were negative for glutamic acid decarboxylase and tyrosine hydroxylase. CR immunoreactivity diminished with development and most large cells of the mitral cell layer were CR-negative in fry. In later embryos and in alevins, CR-ir granule-like cells were observed in the olfactory bulbs. Comparisons of the terminal fields of primary olfactory fibers labeled with CR and with a more general olfactory marker in the olfactory bulbs of fry and adults revealed significant differences, with most glomeruli of the dorsomedial field receiving CR-negative olfactory fibers. These results suggest new criteria for understanding the organization of the olfactory system of the trout, and hence of teleosts. Our results also suggest that CR is involved in specific functions in the olfactory system during development.

Neurobehavioral consequences of cortical adaptation disruption during ontogeny.

Filtering of redundant or stable inputs is a critical function of all sensory pathways. Normal sensory gating can allow processing resources to be differentially devoted to changing or otherwise biologically significant stimuli. In olfaction, short-term odor habituation is mediated by a metabotropic glutamate receptor (mGluR)-mediated depression of afferent synapses in the piriform cortex. Given the role of early experience in shaping cortical function and anatomy, the present experiments examined the effects of chronic habituation disruption during development on behavior and local circuit anatomy. Rats were chronically intra-cerebrally infused with the mGluR group III antagonist (RS)-a-cyclopropyl-4-phosphonophenylglycine (CPPG) during early development. The results demonstrated that early onset mGluRIII blockade resulted in a long-lasting decrement in odor habituation compared to controls, evident for at least 2 weeks post-infusion offset. Odor investigation time in the youngest animals was correlated with cortical laminar thickness, though the long-lasting behavioral effect showed no such correlation. No changes in apical dendritic spine density in the piriform cortex were detected. Combined with previous work, these results suggest that sensory gating disruption during development can have both immediate and long-lasting effects on sensory-guided behavior.

Two types of sensory proliferation patterns underlie the formation of spatially tuned olfactory receptive fields in the cockroach Periplaneta americana.

In the cockroach Periplaneta americana, to represent pheromone source in the receptive space, axon terminals of sex pheromone-receptive olfactory sensory neurons (pSNs) are topographically organized within the primary center, the macroglomerulus, according to the peripheral locations of sex pheromone-receptive single walled (sw)-B sensilla. In this study, we sought to determine when and where pSNs emerge in the nymphal antenna. We revealed two different pSN proliferation patterns that underlie the formation of topographic organization in the macroglomerulus. In nymphal antennae, which lack sw-B sensilla, pSNs are identified in the shorter sensilla, termed sw-A sensilla. Because new sw-A sensilla emerge on the proximal antenna at every molt, topographic organization in the macroglomerulus must be formed by adding axon terminals of newly emerged pSNs to the lateral region in the macroglomerulus at each molt. At the final molt, a huge number of new sw-B sensilla appeared throughout the whole antenna. Sw-B sensilla in the proximal part of the adult antenna were newly formed during the last instar stage, whereas those located in the distal antenna were transformed from sw-A sensilla. This transformation was accompanied by an increase in the number of pSNs. Axon terminals of newborn pSNs in new sw-B sensilla were recruited to the lateral part of the macroglomerulus, whereas those of newborn pSNs in transformed sw-B sensilla were recruited to the macroglomerulus according to the sensillar location. These mechanisms enable an increase in sensitivity to sex pheromone in adulthood while retaining the topographic map formed during the postembryonic development.

The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells.

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existence of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use.