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The distribution and morphology of opioid peptide immunoreactive neurons in the cerebral cortex of rats.

Pharmacological and biochemical evidence has implied that a widespread opioid peptide system exists within the cerebral cortex to mediate a variety of opiate effects. However, immunocytochemical detection of opioid peptides in the cortex has been limited. Using antisera to enkephalin and bovine adrenal medullary peptide, both fragments of proenkephalin, and an antiserum to dynorphin A, a fragment of prodynorphin, we now describe the regional and laminar distribution of a widespread population of olfactory cortical and neocortical cell bodies and fibers with opioid immunoreactivity in rats. Neurons stained with each antiserum are distributed bimodally in layers II and III and V and VI of neocortex as well as in layers II and III of olfactory cortex. The widespread distribution and heterogeneous morphology of cortical cells containing proenkephalin and dynorphin-A immunoreactivity suggest that opioid peptide-containing neurons may influence the functioning of local, commissural, and projection neurons in rat cerebral cortex.

Animals↗

Neurogranin in the development of the rat telencephalon.

We have used a novel antibody to map the distribution of the protein kinase C substrate protein RC3/neurogranin during the development of the rat telencephalon. Neurogranin appearance in the rat brain is biphasic: it shows an early stage of anatomically restricted, low-intensity expression, and a juvenile stage of anatomically widespread, high-intensity expression. Most of the structures that express neurogranin during development conserve it in the adult stage. Neurogranin expression starts on embryonic day 18 in two different sites-the amygdalar primordium and in the piriform cortex-and is confined to these structures until the first postnatal day (P1). On P1, neurogranin expression increases dramatically in intensity, and appears in the olfactory cortex, isocortex, subiculum and hippocampus. In the striatum, expression starts on P1 and extends to the caudoputamen and parts of the globus pallidus and septum. Particularly complex patterns of labelling can be seen in the amygdala and cerebral cortex. Cortical layers showing early expression are the presumptive layers 4 and 5 in the somatosensory cortex, and layers 2 and 5 in the anterior cingulate and agranular insular cortices. Immunoreactivity is found mostly in cell bodies during the early and juvenile stages, but by the end of the first postnatal week it starts being more apparent in the neuropil. This phenomenon probably reflects the intracellular translocation of neurogranin to distal parts of the dendrites and dendritic spines. This process culminates by the end of the second postnatal week, when the adult pattern is reached. According to the timing and anatomy of its distribution, expression of neurogranin seems to be independently regulated in each telencephalic region by specific signalling mechanisms. It is proposed, on this basis, that neurogranin could be implicated in neuronal differentiation and synaptogenesis during telencephalic development.

Aging↗

The prenatal development of the anterior commissure in hamsters: pioneer fibers lead the way.

The prenatal development of the anterior commissure (AC) was studied in 130 hamster embryos with ages varying from E12 to E16 (E1 = day of conception and E16 = P1 = day of birth) by use of carbocyanine crystals (DiI, DiA and/or DiO) implanted into different rostrocaudal segments of the paleocortex. On E12 and E13, many AC axons were seen with tortuous trajectories pointing towards the midline (precrossing stage). On E13.5 and E14, most AC fibers abutted the midsagittal plane, led by a few pioneer axons that grew as far as 500 microns ahead into the opposite hemisphere (crossing stage). Pioneers were present in most brains at these ages irrespective of the rostrocaudal position of the carbocyanine crystal. Somata of pioneer axons could be identified by retrograde labelling. They were characteristically immature neurons, located either in the olfactory peduncle or in the superficial layers of the olfactory cortex. On E14.5 and E15, pioneers and followers were seen close to the targets and on E15.5 and E16 interstitial budding occurred, and arborization started within the olfactory peduncle and the paleocortex (postcrossing stage). If the existence of pioneer fibers represents something more than a stochastic phenomenon, their appearance in the developing AC may reflect the operation of signals at the midline and/or in the contralateral hemisphere that either accelerate the growth of pioneers, or decelerate the growth of followers.

Animals↗

[Electrophysiological analysis of the spectrum of the fibers of the lateral olfactory tract in rats in vitro].

Total action potentials (AP) of lateral olfactory tract (LOT) have been studied on 200 um sections of olfactory cortex of rat brain. Over-threshold stimulation of a proximal end of LOT was accompanied by five waves at descending phase of AP. The increase in stimulation frequency from 1 to 3 to 10 Hz led to a decrease in amplitudes of all LOT AP components. The data obtained suggest that the composition of LOT fibers is heterogeneous.

Action Potentials↗

Multisensory processing via early cortical stages: Connections of the primary auditory cortical field with other sensory systems.

It is still a popular view that primary sensory cortices are unimodal, but recent physiological studies have shown that under certain behavioral conditions primary sensory cortices can also be activated by multiple other modalities. Here, we investigate the anatomical substrate, which may underlie multisensory processes at the level of the primary auditory cortex (field AI), and which may, in turn, enable AI to influence other sensory systems. We approached this issue by means of the axonal transport of the sensitive bidirectional neuronal tracer fluorescein-labeled dextran which was injected into AI of Mongolian gerbils (Meriones unguiculatus). Of the total number of retrogradely labeled cell bodies (i.e. cells of origin of direct projections to AI) found in non-auditory sensory and multisensory brain areas, approximately 40% were in cortical areas and 60% in subcortical structures. Of the cell bodies in the cortical areas about 82% were located in multisensory cortex, viz., the dorsoposterior and ventroposterior, posterior parietal cortex, the claustrum, and the endopiriform nucleus, 10% were located in the primary somatosensory cortex (hindlimb and trunk region), and 8% in secondary visual cortex. The cortical regions with retrogradely labeled cells also contained anterogradely labeled axons and their terminations, i.e. they are also target areas of direct projections from AI. In addition, the primary olfactory cortex was identified as a target area of projections from AI. The laminar pattern of corticocortical connections suggests that AI receives primarily cortical feedback-type inputs and projects in a feedforward manner to its target areas. Of the labeled cell bodies in the subcortical structures, approximately 90% were located in multisensory thalamic, 4% in visual thalamic, and 6% in multisensory lower brainstem structures. At subcortical levels, we observed a similar correspondence of retrogradely labeled cells and anterogradely labeled axons and terminals in visual (posterior limitans thalamic nucleus) and multisensory thalamic nuclei (dorsal and medial division of the medial geniculate body, suprageniculate nucleus, posterior thalamic cell group, zona incerta), and in the multisensory nucleus of the brachium of the inferior colliculus. Retrograde, but not anterograde, labeling was found in the multisensory pontine reticular formation, particularly in the reticulotegmental nucleus of the pons. Conversely, anterograde, but no retrograde, labeling was found in the visual laterodorsal and lateroposterior thalamic nuclei, in the multisensory peripeduncular, posterior intralaminar, and reticular thalamic nuclei, as well as in the multisensory superior and pericentral inferior colliculi (including cuneiform and sagulum nucleus), pontine nuclei, and periaqueductal gray. Our study supports the notion that AI is not merely involved in the analysis of auditory stimulus properties but also in processing of other sensory and multisensory information. Since AI is directly connected to other primary sensory cortices (viz. the somatosensory and olfactory ones) multisensory information is probably also processed in these cortices. This suggests more generally, that primary sensory cortices may not be unimodal.

Afferent Pathways↗

Odor processing in the frog olfactory system.

In the frog, unitary electrophysiological recordings have been extensively used to investigate odor processing along the olfactory pathways. From the responses of primary second-order neurons, neuroreceptor and mitral cells, odor stimuli could be classified in qualitative groups, revealing that neuronal discriminative mechanisms are partly based on the structure of odor molecule. In the olfactory bulb, thanks both to the anatomical convergence of primary afferences and intrinsic network properties, mitral cells have been demonstrated to gain in odor discrimination and detection power abilities. GABAergic bulbar interneurons were found to be involved in the control of mitral cell excitability, adjusting response thresholds and duration and promoting a progressive increase of burst discharges with stimulus concentration. Otherwise, dopamine was observed to shunt off mitral cell spontaneous activity without altering their odor responsivity properties. Dopamine was demonstrated to act through D2 receptors. Matching anatomical and electrophysiological data, D2 receptors are assumed to be localized on mitral cells. The frog olfactory cortex neurons, silent at rest, could be segregated in two functional groups basing on their odor response properties. The first group shared most intensity coding properties with mitral cells while showing a lower discriminative power, similar to that of neuroreceptor cells. By contrast, the second group provided only minimal intensity coding and, basing on its high discrimination power, was assumed to be mainly devoted to odor discrimination. Thus, along the olfactory pathways, intensity and quality odor parameters which are simultaneously encoded by a neuroreceptor or mitral cell, become specified by two distinct populations in the cortex.

Animals↗

The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis.

The origin and termination of fibers to the mediodorsal thalamic nucleus, especially those to the medial, magnocellular part of the nucleus (MDm), have been studied using anterograde and retrograde axonal tracing methods, as well as electrophysiological recording. The results indicate that in addition to its well-known connections to and from the prefrontal cortex, MDm receives fibers from many parts of the basal forebrain, including the ventral pallidum and other parts of the substantia innominata, the amygdaloid complex, the primary olfactory cortex, entorhinal and perirhinal cortex, and the cortex at the pole of the temporal lobe. Lighter projections arise in the subiculum, the ventral insula, and the superior and inferior temporal gyri. The cells that project to MDm tend to be large, polymorphic neurons. Throughout most of the basal forebrain they are diffusely distributed through several nuclei or cortical layers, without obvious relation to nuclear or laminar boundaries. The major exception to this is in the ventral pallidum, where there is a dense concentration of cells that project to MDm. The lateral part of the mediodorsal nucleus (MDl) receives few if any fibers from the basal forebrain and temporal lobe, but is innervated by several brainstem structures, especially the superior colliculus, the substantia nigra, the medial vestibular nucleus, and the midbrain tegmental fields. In MDm, the fibers are distributed in irregular patches. Three-dimensional analysis indicates that these patches are often clustered into separate bands or columns at different anteroposterior levels. In addition, the strongest projections from the three major regions that innervate MDm are organized in a complex three-dimensional pattern. First, the fibers from the amygdaloid nuclei terminate most heavily (but not exclusively) in the rostral third of MDm. The parvicellular accessory basal amygdaloid nucleus and the amygdalohippocampal area project principally to the dorsal part of the nucleus. The parvicellular basal nucleus and the periamygdaloid cortex project to the ventromedial quadrant of MDm; and the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the lateral nucleus all project to the ventrolateral quadrant. Second, the substantia innominata projects preferentially to the caudal part of MDm. The medial part of the substantia innominata, especially the ventral pallidum, innervates the dorsomedial quadrant, while more caudal and lateral areas of this region project ventrolaterally. Third, the projections arising from the entorhinal and other temporal cortical areas terminate primarily in the mid-rostrocaudal level of MDm.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Binding of gamma-aminobutyric acid and taurine to synaptosomal fractions of regions of the feline CNS.

The "binding" of 3H-gamma-aminobutyric acid (3H-GABA) and 14C-taurine (7 X 10(-5) M) to synaptosomal fractions of the feline CNS was studied using differential centrifugation and double-isotope methods. Of the regions examined, the "binding" of GABA (in nmole/mg protein) occurred to the greatest extent, in cerebral cortex, olfactory bulb, and colliculi and, to a lesser extent, in caudate nucleus, corona radiata, and fornix. Distribution ratios revealed that GABA binding was greater in the cerebral cortex than in caudate nucleus, brain stem, spinal cord, and white matter regions. The binding of taurine (in nmole/mg protein) was lowest in cerebral cortex and highest in brain stem and spinal gray regions. Distribution ratios for taurine indicated that its accumulation was similar in all CNS regions studied, except for slightly higher values for cerebellar cortex and fornix. These results indicated that preferential binding of both GABA and taurine exists among regions of the feline CNS.

Aminobutyrates↗

Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18.

The detailed microanatomical study of the human cerebral cortex began in 1899 with the experiments of Santiago Ramón y Cajal, who applied the Golgi method to define the structure of the visual, motor, auditory and olfactory cortex. In the first article of this series, he described a special type of interneuron in the visual cortex capable of exerting its influence in the vertical dimension. These neurons are now more commonly referred to as double-bouquet cells (DBCs). The DBCs are readily distinguished owing to their characteristic axons that give rise to tightly interwoven bundles of long, vertically oriented axonal collaterals resembling a horsetail (DBC horsetail). Nevertheless, the most striking characteristic of these neurons is that they are so numerous and regularly distributed that the DBC horsetails form a microcolumnar structure. In addition, DBCs establish hundreds of inhibitory synapses within a very narrow column of cortical tissue. These features have generated considerable interest in DBCs over recent years, principally among those researchers interested in the analysis of cortical circuits. In the present chapter, we shall discuss the morphology, synaptic connections and neurochemical features of DBCs that have been defined through the study of these cells in different cortical areas and species. We will mainly consider the immunocytochemical studies of DBCs that have been carried out in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see that there are important differences in the morphology, number and distribution of DBC horsetails between areas 17 and 18 in the primate. This suggests important differences in the microcolumnar organization between these areas, the functional significance of which awaits detailed correlative physiological and microanatomical studies.

Animals↗

High levels of ascorbic acid, not glutathione, in the CNS of anoxia-tolerant reptiles contrasted with levels in anoxia-intolerant species.

Ascorbic acid and glutathione (GSH) are antioxidants and free radical scavengers that provide the first line of defense against oxidative damage in the CNS. Using HPLC with electrochemical detection, we determined tissue contents of these antioxidants in brain and spinal cord in species with varying abilities to tolerate anoxia, including anoxia-tolerant pond and box turtles, moderately tolerant garter snakes, anoxia-intolerant clawed frogs (Xenopus laevis), and intolerant Long-Evans hooded rats. These data were compared with ascorbate and GSH levels in selected regions of guinea pig CNS, human cortex, and values from the literature. Ascorbate levels in turtles were typically 100% higher than those in rat. Cortex, olfactory bulb, and dorsal ventricular ridge had the highest content in turtle, 5-6 mumol g-1 of tissue wet weight, which was twice that in rat cortex (2.82 +/- 0.05 mumol g-1) and threefold greater than in guinea pig cortex (1.71 +/- 0.03 mumol g-1). Regionally distinct levels (2-4 mumol g-1) were found in turtle cerebellum, optic lobe, brainstem, and spinal cord, with a decreasing anterior-to-posterior gradient. Ascorbate was lowest in white matter (optic nerve) in each species. Snake cortex and brainstem had significantly higher ascorbate levels than in rat or guinea pig, although other regions had comparable or lower levels. Frog ascorbate was generally in an intermediate range between that in rat and guinea pig. In contrast to ascorbate, GSH levels in anoxia-tolerant turtles, 2-3 mumol g-1 of tissue wet weight, were similar to those in mammalian or amphibian brain, with no consistent pattern associated with anoxia tolerance. GSH levels in pond turtle CNS were significantly higher (by 10-20%) than in rat for several regions but were generally lower than in guinea pig or frog. GSH in box turtle and snake CNS were the same or lower than in rat or guinea pig. The distribution GSH in the CNS also had a decreasing anterior-to-posterior gradient but with less variability than ascorbate: levels were similar in optic nerve, brainstem, and spinal cord. The paradoxically high levels of ascorbate in turtle brain, which has a lower rate of oxidative metabolism than mammalian, suggest that ascorbate is an essential cerebral antioxidant. High levels may have evolved to protect cells from oxidative damage when aerobic metabolism resumes after a hypoxic dive.

Adaptation, Physiological↗

Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study.

Neuropathological studies of 10 confirmed cases of Alzheimer's disease (AD) revealed increased numbers of neurofibrillary tangles and neuritic plaques in olfactory cortex compared to other brain regions. This was most evident when AD tissues were compared to tissues from seven gender- and age-matched controls. In the AD cases, examination of other brain regions which receive olfactory projections also revealed high concentrations of neuritic plaques and neurofibrillary tangles. These data also confirm previous observations that neurofibrillary tangle formation is more prevalent than neuritic plaque formation in AD. This is the first quantitative neuropathological study that demonstrates significant damage to various components of the central olfactory apparatus in AD. Our data suggest that damage to these areas may be related to the behavioral, emotional, and cognitive abnormalities commonly observed in affected patients. The use of antemortem evaluation of the olfactory system as a diagnostic tool for AD is discussed.

Aged↗

Passive perception of odors and semantic circuits.

The sense of smell has been traditionally assumed to be different from other sensory modalities in that odors are encoded perceptually, without a semantic component. Recent findings of improved odor memory upon encoding with verbal cues question this view. Furthermore, familiar odors are easier to remember and discriminate than are unfamiliar ones, and odor familiarity is reported to predict odor naming. To investigate whether familiar odors are processed by different cerebral structures than those that process unfamiliar odors, (15)O H(2)O-positron emission tomography (PET) measurements of cerebral blood flow were carried out in 14 healthy men. The task was passive, birhinal, smelling of familiar odors (FAM), unfamiliar odors (uFAM), and odorless air (AIR). Significant activations (P < 0.05) were calculated using the contrasts FAM-AIR, uFAM-AIR, and FAM-uFAM, and deactivations running these contrasts in the opposite direction. In relation to AIR, both FAM and uFAM activated amygdala, piriform cortex, and parts of anterior cingulate cortex. FAM activated, in addition, left frontal cortex (Brodmann's areas 44,45,47), left parietal cortex incorporating precuneus, and right parahippocampus. Clusters covering parahippocampus and precuneus were observed also in FAM-uFAM. The activation of left frontal cortex and right parahippocampus was positively correlated with familiarity ratings. Smelling of familiar but not unfamiliar odorants seems to engage cerebral circuits mediating memory and language functions, in addition to the engagement of olfactory cortex. Already the most elemental form of odor processing, passive perception thus seems to engage semantic circuits. This is achieved by the ability of odorants to immediately elicit associations and judgments of odor characteristics.

Adult↗

AMPA autoreceptors drive correlated spiking in olfactory bulb glomeruli.

Information processing in the brain may rely on temporal correlations in spike activity between neurons. Within the olfactory bulb, correlated spiking in output mitral cells could affect the odor code by either binding or amplifying signals from individual odorant receptors. We examined the timing of spike trains in mitral cells of rat olfactory bulb slices. Depolarization of mitral cell pairs elicited spikes that were correlated on a rapid timescale (< or =10 ms) for cells whose primary dendrites projected to the same glomerulus. Correlated spiking was driven by a novel mechanism that depended on electrical coupling at mitral cell primary dendrites; the specific synchronizing signal was a coupled depolarization ( approximately 20 ms) that was mediated by dendritic AMPA autoreceptors. We suggest that glomerulus-specific correlated spiking in mitral cells helps to preserve the fidelity of odor signals that are delivered to the olfactory cortex.

Action Potentials↗

Synaptophysin and synaptoporin expression in the developing rat olfactory system.

The expressions of two closely related synaptic vesicle antigens synaptophysin and synaptoporin were examined in the olfactory system of the adult rat and during pre- and postnatal development. In the adult, immunocytochemistry showed that the continuously regenerating olfactory receptor neurons (primary neurons) produce both synaptophysin and synaptoporin which were localized in the cell bodies of the receptor neurons in the olfactory epithelium, their dendrites, axonal processes in the olfactory nerve and their terminals in the olfactory bulb glomeruli. Furthermore, ultrastructural analysis revealed synaptophysin- and synaptoporin-immunoreactivities associated with synaptic vesicles in most olfactory receptor axonal terminals impinging on dendrites of the mitral and tufted neurons (secondary neurons in the olfactory bulb circuitry) in the olfactory glomeruli. In like manner, tufted neurons, granule and periglomerular neurons (interneurons in the olfactory bulb circuitry) express both synaptophysin and synaptoporin. In contrast, mitral neurons expressed only the synaptophysin antigen which was likewise associated with mitral axonal terminals in their target the olfactory cortex. The patterns of synaptophysin and synaptoporin expressions in mitral neurons (synaptophysin only) and tufted neurons (synaptophysin and synaptoporin) were similar in prenatal, postnatal and adult rats as revealed by immunocytochemistry and in situ hybridization. However, the biosynthesis of synaptophysin and synaptoporin by granule and periglomerular neurons, olfactory bulb interneurons, occurred mainly postnatally.

Animals↗

Low and moderate doses of ethanol produce distinct patterns of cerebral metabolic changes in rats.

The quantitative autoradiographic 2-[14C]deoxyglucose method was used to measure the effects of the acute administration of ethanol on local rates of glucose utilization in male Sprague-Dawley rats. Rates of glucose utilization were measured 10 min after the intraperitoneal administration of 0.00, 0.25, 0.50, and 1.00 g/kg ethanol. The acute administration of the lowest dose of ethanol (0.25 g/kg) significantly increased rates of cerebral metabolism, as compared with vehicle-treated controls, in structures of the mesocorticolimbic and nigrostriatal dopaminergic systems. Among the affected regions were the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, caudate, ventral tegmental area, and substantia nigra. Acute administration of 0.50 g/kg ethanol resulted in similar trends in increased functional activity; however, significant increases were limited to the somatosensory cortex, posterior nucleus accumbens, and the CA3 region of the hippocampus. In contrast, the administration of 1.00 g/kg ethanol produced widespread decreases in rates of glucose utilization in brain regions involved in processing of sensory and motor information, as well as in portions of the limbic system. These data indicate that the effects of acute ethanol administration on functional activity as reflected by rates of glucose utilization are dose-dependent. These cerebral metabolic effects parallel the dose-dependent effects of ethanol on motor behavior, with stimulatory effects generally observed at lower doses and depressive effects at higher doses. Moreover, each of the doses studied produced alterations in functional activity in a unique subset of structures. This suggests that different neuroanatomical circuits mediate the effects of each dose.

Alcoholic Intoxication↗

Comparative aspects of forebrain organization in the ray-finned fishes: touchstones or not?

The comparative interpretation of forebrain organization of the ray-finned fishes presents a number of challenges. The telencephalon develops by an eversion process, and much of its surface is ventricular rather than pial. A topological map of the ventricular surface shows that the area ventralis (presumed subpallium) is bordered dorsally by the dorsomedial (DM) zone of the area dorsalis, which is, in turn, bordered by the olfactory-recipient dorsoposterior (DP) zone of the area dorsalis. Within the diencephalon small dorsal and ventral thalami and a large group of migrated nuclei assigned to the posterior tuberculum (but of uncertain status) are present. Both the dorsal thalamus and the migrated nuclei of the posterior tuberculum project to the telencephalon. A review of the known connections of the four major zones of the area dorsalis together with their topological positions leads to the following tentative interpretations. Zone DP is homologous to the primary olfactory cortex. There is not enough information concerning the dorsodorsal zone (DD) to speculate on its comparative relationships. Zone DM is a limbic-like area lying between the subpallium and the olfactory pallium and is possibly homologous to the pallial amygdala. The dorsolateral zone (DL) displays a pattern of connectivity with the cerebellum and the optic tectum suggesting a possible homology with non-olfactory, non-limbic pallial areas. Caveats are raised concerning the above interpretations of DM and DL. One or both of them may have evolved independently of the telencephalic zones in tetrapods and may thus represent examples of homoplasy.

Animals↗

The Projections of Mitral Cells from Small Local Regions of the Olfactory Bulb: An Anterograde Tracing Study Using PHA-L (Phaseolus vulgaris Leucoagglutinin).

Numerous anatomical and electrophysiological studies have demonstrated a lack of simple point-to-point topographical relationships between the olfactory bulb and primary olfactory projection areas. They reveal instead, a complex pattern of divergence and convergence. Furthermore, several authors reported that a single mitral cell could project onto different widely spaced cortical regions of the olfactory cortex. In the present study, we attempted to label the projections of a few mitral cells so close together so that they might be assumed to be connected to the same glomerulus, and to determine if these cells had similar patterns of axonal projections. For this purpose small Phaseolus vulgaris leucoagglutinin (PHA-L) injections were performed in the olfactory bulb of adult rats. We found that labelling two to five mitral cells, lying close together in the mitral cell layer, resulted in well-delineated patches of labelled fibres in the cortex. The number of patches was not related to the number of labelled mitral cells but the fibre density in each patch increased with the number of PHA-L filled somata in the olfactory bulb. We conclude that mitral cells lying close together in the mitral cell layer have similar patterns of axonal projections. Functional implications of such an organization in olfactory coding is discussed.

Journal Article↗

Early onset of the rat olfactory bulb projections.

Using the fluorescent carbocyanine tracer DiI, we examined in detail the early development of the projections emanating from the rat olfactory bulb. The study commenced at embryonic day 13 when the first fibres can be detected and ended at embryonic day 20, when all major fibre systems have been established. The first axons arising from the prospective olfactory bulb area are seen at embryonic day 13. Labelled fibres are provided with elaborate axonal growth cones advancing through the ventrolateral part of the telencephalic vesicle. At embryonic day 14, while the main fibre tract has not developed much further, some isolated fibres are located quite distally from the prospective olfactory bulb. These early fibres apparently course within a narrow cell-free space that extends caudally along the ventrolateral part of the telencephalic vesicle. At embryonic day 15, a number of labelled fibres form a compact bundle, corresponding to the lateral olfactory tract, that ultimately reaches the prospective primary olfactory cortex. The fibres do not stop growing, but continue to extend caudally at embryonic day 17. The results of this study provide new information on the development of axonal tracts in the olfactory system. We show that the olfactory tract projection develops earlier than the morphological appearance of the olfactory bulbs. This suggests that the early development of olfactory projections might not depend on the arrival of the olfactory epithelium axons and thus, could be governed by factors intrinsic to the neurons and/or cues present in the target environment.

Animals↗