Abstract: The [‘4C]2-deoxy-D-glucose (2DG) technique was employed to study the ontogeny of functional organization in the olfactory bulbs of rats from birth to 21 days postnatal. These observations were correlated with the histological maturation of the olfactory bulb laminae. In O-day pups (within 12 hr of parturition), foci of increased metabolic activity were elicited in the olfactory bulb by the odor of amyl acetate. The foci, generally poorly defined, were localized over the glomerular layer, which, in histological sections, was poorly differentiated. In suckling pups injected with 2DG, a single focus characteristically was observed in the main olfactory bulb near the medial border of the accessory olfactory bulb. In this region, a well differentiated complex of glomeruli was observed in the histological sections. During the ensuing 21 days postnatal, the focal patterns of 2DG uptake in animals exposed to amyl acetate odor progressed through a series of changes, each of which could be related to parallel stages of development in the histology of the bulb. Particularly striking were the establishment of sharply defined 2DG foci and the formation of distinct individual olfactory glomeruli by the end of the 1st week. Generally, by 15 days postnatal, the adult patterns of 2DG uptake and histological lamination were established. The modified glomerular complex also exhibited focal 2DG uptake beginning on day 0, but these were better defined than those associated with the glomeruli of the main olfactory bulb. This observation correlated with the more advanced histological differentiation of this specialized region. These data suggest that the modified glomerular complex may mature earlier than other regions of the olfactory bulb. This earlier maturation may reflect the importance of the modified glomerular region for processing odor cues relevant to suckling behavior in neonatal rats. Taken together, these results provide evidence for several successive changes in the functional organization of the developing olfactory system of neonatal rats. The neural substrates of olfactory function in the neonatal rat are not well understood. Behavioral studies generally agree upon the critical role of olfaction during the perinatal period of development (Blass and Teicher, I We would like to thank Dr. John S. Kauer for valuable discussions and development of the computer-assisted reflectance densitometry program, Dolores Montoya and Janina Casby for their excellent technical assistance, and Kathleen Kiley for secretarial assistance. This research was supported in part by National Institute of Neurological and Communicative Disorders and Stroke Grant F32-NS06159 to C. A. G., National Science Foundation Grant BNS-78-16545 to G. M. S., and National Institutes of Health Grant NS-10174 to William F. Collins. 1744 1980; Teicher and Blass, 1976, 1978; Leon, 1974). Although olfactory function can be demonstrated in the neonate, acuity is low (Rudy and Cheatle, 1977; Alberts and May, 1980a, b). In electrophysiological studies, spontaneous EEG activity has not been observed in the rat olfactory bulb prior to 3 days postnatal (Salas et al., 1969), although single unit analyses report spontaneous mitral cell activity within 12 hr postnatal (Math and Davrainville, 1980a, b) . ’ To whom correspondence should be addressed at Section of Neuroanatomy, Yale University School of Medicine, 333 Cedar Street, New

Abstract: Large Amounts of cholecystokinin-octapeptide (CCK) are present in the rat caudatoputamen. The peptide occurs in axons and nerve endings but not in perikarya. The origin of CCK in the caudatoputamen was investigated with the use of immunocytochemistry and a radioimmunoassay specific for CCK. Although a small amount of CCK (approximately 30 percent) originates in the amygdaloid complex, the bulk of the peptide (approximately 70 percent) occurs in processes of neurons located ventral to the caudatoputamen, that is, the claustrum or the piriform cortex. The claustrum and piriform cortex receive inputs from various cortical areas and the olfactory system, respectively, and may process information and relay it to the caudatoputamen. Thus CCK may by the transmitter in the final common pathway linking various cortical areas and the olfactory system to the caudatoputamen.

Abstract: Following an olfactory bulb lesion in guinea pig (2 to 3 days), neuronal degeneration occurs in several olfactory-bulb-related areas, primarily in the piriform cortex. The degenerating neurons, which are argyrophilic, are also found in the posterolateral cortical amygdaloid nucleus and the ventrolateral entorhinal cortex. It is suggested that the neurons degenerate because of a transneuronal effect due to a sudden loss of afferent input from the the olfactory bulb, although a retrograde effect acting in concert with transneuronal factors cannot be excluded. Terminal degeneration can be identified in several areas outside the olfactory bulb projection area, and is interpreted as degeneration in the axons of the degenerating cortical neurons. Such terminal degeneration, which is best seen 3 to 4 days postoperatively, has been identified in part of the basolateral amygdaloid complex, in the basomedial amygdaloid nucleus, and in the temporal parts of the fascia dentata of the hippocampal formation. Terminal degeneration has also been observed in the deep layers of the anterior olfactory nucleus, the olfactory tubercle, the nucleus of the lateral olfactory tract, and the anterior amygdaloid area. All these projections, apparently, represent the second link in two-neuron pathways, where mitral or tufted cells in the olfactory bulb make up the first neuron. This interpretation was confirmed in control experiments in which areas of argyrophilic neurons coincided with the location of retrogradely labeled neurons following injection of flurorescent substances into several of the abovementioned areas of terminal degeneration.

Abstract: Previous in vivo studies have shown that beta-alanine is incorporated specifically into the dipeptide L-carnosine (beta-alanyl-L-histidine). In the present study, we administered beta-[3H]alanine to the nasal cavity of hamsters and used biochemical analyses to identify the radioactively labeled compounds in the olfactory epithelium and olfactory bulb and autoradiography to demonstrate the localization and transport of the label in the primary afferents of the olfactory system. The olfactory epithelium and lamina propria were labeled intensely 6 hr after intranasal beta-[3H]alanine administration. At this survival time, 61% of the radioactivity in the olfactory epithelium was present in the carnosine fraction, while 37% of the label remained in the beta-alanine fraction. After 24-hr and 4-day survival periods, greater than 82% of the radioactivity was present in the carnosine fraction, and the olfactory receptors and bundles of axons were labeled preferentially. The olfactory nerve and glomerular layers of the main olfactory bulb were labeled intensely at 6 and 24 hr after beta-[3H]alanine administration; much less label was present in these layers at 4 days survival. At all three of these survival times, greater than 84% of the radioactivity in the olfactory bulb was present in the carnosine fraction. No label was present in the olfactory epithelium or bulb 18 days after beta-[3H]alanine administration. While the autoradiographic labeling over the structures of the accessory olfactory system was consistently less intense than that over the main olfactory system structures, the patterns of labeling were similar over the four survival times. Intranasal alpha-[3H]alanine administration resulted in some labeling in the primary afferent fibers, but the labeling did not have the specificity nor the same time course over the four survival times that was observed after beta-[3H]alanine administration. The results are consistent with the hypothesis that carnosine is a neurotransmitter or neuromodulator in the olfactory neurons. The results also suggest that carnosine may play a similar role in the vomeronasal neurons.

Abstract: The primary sensory neurons in the olfactory and vomeronasal mucosae develop outside the neuraxis from ectodermal placodes, and their axons enter the central nervous system (CNS) during embryonic life, to terminate in the olfactory and accessory olfactory bulbs. The sensory neurons are unique in that they are produced and differentiate continuously from a stem cell in the sensory epithelium, throughout the life of the animal. After loss of sensory neurons following injury, the stem cell is able to increase its rate of division and replace the lost neurons. Sensory neurons thus formed during adult life, in the normal animal or after injury, possess another important and unique property: they are able to grow axons which can re-enter the CNS. Once in the CNS they can re-establish synaptic contact with central neurons. Such regenerative growth can result in re-establishment of connections between sensory mucosa and olfactory bulb in the adult animal, and a consequent recovery of olfactory function after injury to the pathway. However, a 'normal' pattern of connections is not always re-established, and olfactory axons may regenerate into areas of the CNS which they never enter during normal development. The special qualities which allow olfactory axons to re-enter the CNS are not known. Current work is aimed at examining more closely the interface where the peripheral nerve meets the CNS. Preliminary results suggest that this interface may be hard to define: the olfactory nerves themselves, although classically regarded as peripheral nerves, possess some features of central tracts, since their glia contain the astrocyte-specific protein GFAP, and resemble astrocytes in fine structure.

Abstract: 1. Electrophysiological responses were obtained from the peripheral olfactory system of the American eel,Anguilla rostrata, using three different recording methods: averaged multiunit activity from the olfactory mucosa (MNR), averaged multiunit activity from bundles of olfactory nerve axons (NTR), and the underwater electro-olfactogram (EOG). 2. For each of the three techniques, response magnitude increased exponentially with logarithmic increase in stimulus concentration, denoting a power function (Figs. 2, 3). 3. Thresholds forl-glutamine, determined from NTR, MNR, and EOG recordings, were 10−9.6±0.3mol/l, 10−8.0±0.2mol/l and 10−7.8±0.2 mol/l, respectively. The difference between the NTR and the EOG and MNR thresholds was significant while the difference between EOG and MNR thresholds was not (Table 2). 4. Gamma, the reciprocal of the power function exponent, which is the number of log steps of concentration necessary to produce a tenfold increase in response magnitude, was 10.3±0.4 for the NTR, 6.5±0.4 for the MNR, and 5.3±0.2 for the EOG. The difference between the NTR gamma and the EOG and MNR gammas was significant while the difference between the EOG and MNR gammas was not (Table 2). 5. There was a significant correlation between the relative stimulus effectiveness for 11 amino acids determined with each of the three methods (Fig. 4). 6. An amino acid with 5 or 6 carbon atoms, a linear side chain, and an unsubstituted hydrogen and amino group in the alpha position was generally a highly effective olfactory stimulus. 7. Esterification of the primary carboxyl group ofl-alanine did not result in a loss of stimulatory effectiveness, indicating that a charged carboxyl group may not be necessary for maximal stimulation.

Abstract: Development of the vomeronasal organ in the golden hamster was chronologically examined by light and electron microscopy. This organ was embryologically derived from the olfactory placode and appeared as a tubular structure of the neuroepithelium on the medial wall of the nasal pit on either side at 11 days of gestation. At 12 days of gestation, this organ was completely separated from the nasal cavity and encircled by the immature vomeronasal cartilage. At 13 days of gestation, within the organ, the respiratory epithelium became easily distinguishable from the sensory epithelium. At 14 days of gestation the venous sinus and Jacobson's glands appeared, and this organ was equipped with all the histological components until birth. This organ began to communicate with the nasal cavity at 2 days after birth. The sensoly epithelium of this organ consisted of undifferentiated cells in the early fetal life. These stem cells were gradually differentiated into sensory and supporting cells. These cells were rather slowly maturated in their fine structure. For example, only some sensory cells became first provided with microvilli on their free surface at 8 days after birth. Even at 10 days after birth, some sensory cells were still devoid of microvilli and undifferentiated cells were sometimes observed in the sensory epithelium as well. Therefore, the olfactory function in the early postnatal life seems to be solely ascribed to the olfactory epithelium under these morphodifferentiation though the vomeronasal organ might be related with some kind of olfaction after this period.

Abstract: Mice were trained to discriminate between scented and unscented air. After olfactory bulbs were removed, discrimination was lost, but returned with the formation of synaptic connections between regenerated primary olfactory neurons and the cortex of the forebrain. The acquisition of a second olfactory-mediated task by long-term bulbectomized mice and controls was indistinguishable. The results emphasize the plasticity of the nervous system, correlate the presence of neural connections between olfactory mucosa and forebrain with the recovery of olfactory function, suggest that olfactory-mediated memory resides at least in part outside the olfactory bulbs, and demonstrate that the bulbs are not required for the acquisition of olfactory tasks.

Abstract: The development of the olfactory epithelium in 7-, 8-, 9-, 10- and 11-week-old human fetuses was studied by electron microscopy. The differentiation of the receptor and supporting cells, and formation of the Bowman glands and the olfactory nerve were observed. In 7-week-old fetuses develop the peripheral processes with the olfactory knobs lacking hairs, as well as the central processes with the growth cones. The olfactory knob with hairs was first found in 9-week-old fetuses, their number progressively increasing starting from the 10th week. The completely differentiated olfactory cells were found by the 11th week. They are suggested to be capable to carry out the olfactory function.

Abstract: Two experiments were conducted to determine (a) whether male garter snakes (Thamnophis sirtalis) require a functional vomeronasal or olfactory system to return to previously preferred shelter locations and (b) the sensory modalities used by snakes to aggregate in the absence of previously deposited chemical cues. In Experiment 1, snakes with vomeronasal nerve lesions did not return to previously preferred shelter locations when tested individually. However, when tested with a group that included "control" animals, they returned to previously preferred shelters. The shelter-selection behavior of snakes with olfactory nerve lesions improved postoperatively, whereas the behavior of animals with sham lesions was unchanged. In Experiment 2, snakes were tested for aggregation in aquaria in which the substrate and other contents were cleaned between trials. After blindfolding or after olfactory nerve cuts, snakes aggregated at normal levels. When the snakes' vomeronasal ducts were sutured closed, aggregation scores were significantly depressed, although two of the three groups with vomeronasal duct sutures did aggregate just above chance levels. These studies indicate that use of chemical signals by garter snakes in shelter selection and aggregation is mediated by the vomeronasal system and that neither the olfactory nor the visual system is critical for these behaviors.

Abstract: We examined the effect of heating on electrical activity of neurons in the guinea pig olfactory cortex slice. At the control temperature (37° C) the potential evoked by stimulation of the lateral olfactory tract consisted of an initial spike (IS) potential and a negative (N) potential. The IS potential is considered to be presynaptic and the other transsynaptic.

Abstract: Vertebrate olfactory and gustatory receptors are necessarily exposed to the fluid which contains their relevant chemosensory environment. In terrestrial mammals, the nasal airways serve as protecti...

Abstract: Freeze-fracture data on antennal olfactory and labellar gustatory sensilla of the blowfly Calliphora vicina were compared with those of vertebrate olfactory organs

Abstract: The anatomy, physiology and function of the olfactory system are reviewed, as are the normal effects of olfactory stimulation. It is speculated that olfaction may have important but unobtrusive effects on human behavior.

Abstract: Evidence has mounted that kainic acid (KA), a powerful neuroexcitatory and neurotoxic agent, acts at a specific class of receptors distinct from those mediating the excitatory actions of glutamate1–3. This has prompted a search for the endogenous ligand for the KA-specific receptors. Recently, Ruck et al.4 reported that the naturally occurring folic acid derivative methyltetrahydrofolate (MTHF) is a potent and specific competitor for KA-binding sites in rat cerebellar membranes, having one-tenth the binding activity of KA at these sites. They suggested that MTHF may be the endogenous KA receptor ligand. Olney et al.5 found that injections of various folates—MTHF, folic acid (pteroyl-L-glutamic acid, PGA), or folinic acid (formyltetrahydrofolate, FTHF)—into rat amygdala and striatum produced KA-like seizures and associated brain damage at sites distant from the site of injection. However, these folates did not mimic the direct neurotoxic effects of KA at the injection site. Furthermore, Roberts et al.6 reported that MTHF injected into rat cerebellum produced slower and less complete neuronal degeneration than did KA and, unlike KA and glutamate, did not increase cerebellar cyclic GMP levels. In light of the contradictory results from these binding, histological and biochemical studies, we have tested the electrophysiological equivalency of KA and the folates in rat olfactory cortex slices. KA is a potent agonist at the receptors of the terminal synapses of the lateral olfactory tract (LOT); in fact, the natural transmitter at this synapse appears to act at a KA-preferring receptor7. Also, olfactory cortex is extremely sensitive to the neurotoxic action of KA8. We report here that MTHF, FTHF and PGA had little or no effect on LOT-stimulated field potentials even at millimolar concentrations, whereas KA exhibited excitatory effects at concentrations as low as 5×10−7 M. It therefore seems unlikely that MTHF or the other folates are endogenous ligands for the KA receptor in olfactory cortex.