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PubMed2002

PAX6 in sensory development.

PAX6 function was first identified through aniridia-associated null mutations. Since then, this transcription factor, with a paired domain and a homeodomain, has become a paradigm, illustrating functional conservation in developmental pathways. The Small eye mouse and Drosophila eyeless have served as major model systems in defining the multistage roles for Pax6 in eye and olfactory system development throughout evolution. The overt phenotypic consequences of heterozygous human and mouse Pax6 mutations were initially confined to the eye, with some interesting genotype-phenotype correlations being noted. Recently, structural and functional abnormalities in the olfactory system have been identified. Alterations in brain structure have also been documented, in line with the wider forebrain and cerebellar expression of Pax6. The broad PAX6 expression pattern is controlled by a number of long-range control elements, and is reflected in the severe homozygote phenotype. Upstream regulators and a multitude of downstream targets of PAX6 have been identified, and its varied tissue-specific functions are emerging.

Amino Acid Sequence↗
PubMed1980

[Activation of afferent pathways and of control frog olfactory bulb and extracellular field potentials].

It has been recorded the extracellular field potentials of the frog's olfactory bulb produced by electrical stimulation of the commissura anterior and small branches of the olfactory nerve. The activation of the commissural system obtain a positive, long-lasting field potential generated at the soma of the granular cells. The olfactory nerve stimulation produce also a positive surface wave bath at the end of bulbar reply: this effect can be attributed to the activation of the bulbar component of commissural system at the NOA. The recognizable electrical effects of the commissural system allow to make clear the sources of the extracellular field potentials in the bulbar neuronal circuits.

Action Potentials↗
PubMed1999

Role of polysialic acid on outgrowth of rat olfactory receptor neurons.

Towards elucidating the role of polysialic acid (PSA) in developing olfactory neuron of the rat, we injected neuraminidase (endo-N) into the olfactory nerve pathway under whole embryo culture, then employed immunohistochemistry to (i) detect expression of highly sialylated neural cell adhesion molecules (NCAM-H) and (ii) identify olfactory neurons via anti-microtubule-associated protein 1B (MAP1B) antibody. Olfactory axonal outgrowth from basal lamina occurred at the 31-somite stage and reached the olfactory bulb primordium at the 42-somite stage, being coincident with the timing and expression of NCAM-H immunoreactivity. Enzymatic removal of PSA by endo-N remarkably affected developmental processes of axonal outgrowth, extension, and pathfinding, i.e. individual axons appeared to have become stuck in the mesenchyme. Results indicate that PSA is critically involved with anti-adhesion cues associated with individual axonal growth during olfactory system development.

Animals↗
PubMed1981

Connections of the olfactory bulb in the piranha (Serrasalmus nattereri).

The connections of the olfactory bulb were studied in the piranha using the Nauta and horseradish-peroxidase methods. Three olfactory tracts project to seven terminal fields in the telencephalon and one in the diencephalon, all of them bilaterally. The contralateral olfactory bulb also receives a small input. All contralateral projections decussate in the anterior commissure and are relatively weak compared to the ipsilateral projections. HRP-containing cells were found in all of the ipsilateral telencephalic aggregates receiving an olfactory tract projection; the contralateral side was free of labeled cell bodies. Although only about one fourth of the entire telencephalon receives a direct olfactory input, the high degree of differentiation of the olfactory system suggests that the piranha depends substantially on the sense of olfaction and that this species may be a good model for further studies on olfactory mechanisms.

Animals↗
PubMed1998

Medium- and long-term effects of repeated bicuculline-induced seizures in developing rats on local cerebral energy metabolism.

To assess long-term metabolic consequences of recurrent ictal events arising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i.p. injections of bicuculline for three consecutive days, starting from postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cerebral metabolic rates for glucose were measured in 74 structures at P15, P25 and in adults (P60), by the autoradiographic method using 2-D-[14C]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reduction (16-34%) of glucose consumption at P15, mainly significant in sensory, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%). Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced metabolic rates for glucose (by 7-27%) at P25, significant in 23 structures, and depicting pronounced changes in limbic, hypothalamic, sensory and white matter areas, whereas brain functional activity finally returned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older animals, the reverse was true for long-term metabolic effects, and the more immature the brain when seizures arise, the more persistent the functional consequences.

Aging↗
PubMed1993

Organization of cortical afferent input to orbitofrontal areas in the rhesus monkey.

Odorant signal processing takes place in a diverse group of primary olfactory areas which receive direct input from the olfactory bulb. Orbitofrontal cortices participate in olfactory functions, but the pathways through which they receive olfactory or other input have not been clearly defined. The retrograde tracers horseradish peroxidase and fluorescent dyes were injected in orbital cortices to study their afferent cortical connections. Labeled neurons in primary olfactory areas (prepiriform cortex, anterior olfactory nucleus and olfactory tubercle) were directed mainly to a posterior orbitofrontal region and to a lesser extent the neighboring caudal part of area 13. There was no evidence of direct projections from primary olfactory areas to the rostral parts of area 13, or to areas 12 or 11. Most labeled neurons in primary olfactory areas were directed to agranular cortices, fewer projected to dysgranular areas, and there was no evidence that any reached granular cortices. The areas which received the most robust olfactory projections showed the lowest degree of laminar organization among prefrontal cortices. Early processing in the olfactory system thus takes place in areas which differ sharply on structural grounds from "early" eulaminate post-Rolandic sensory cortices. In addition to olfactory cortical projections, numerous labeled neurons in transitional (limbic) cortices were directed to orbital areas, and fewer but still substantial numbers of afferent neurons were found in eulaminate cortices. Unlike post-Rolandic unimodal sensory areas, which seems to be committed to the processing of input from one sensory modality via sequential and/or parallel pathways, caudal orbital areas received highly distributed input from primary olfactory areas, and in addition, from gustatory, visual, auditory and somatosensory areas. The structural and connectional features of olfactory recipient orbital cortices thus differ markedly from those observed in other sensory association areas and suggest a mode of processing adapted early in cortical evolution.

Animals↗
PubMed1987

Induction and maintenance of epileptiform activity in the rabbit olfactory bulb depends on centrifugal input.

A technique of cryogenic blockade was used in waking rabbits to produce complete and reversible isolation of the olfactory bulb from the rest of the brain. During cooling of the olfactory peduncle epileptiform activity occurred spontaneously in the pyriform cortex in 3 out of 20 sessions, but never in the bulb. Following removal of the cryoblockade, during the seizure state, epileptiform discharges appeared simultaneously in the bulb and pyriform cortex. In the control state, without cooling of the peduncle, epileptiform activity could be evoked in the bulb and cortex by intense electrical stimulation of either the bulb or the lateral olfactory tract. During the cryoblockade, however, intense stimulation of the bulb failed to evoke seizure-like discharges. The results demonstrate a dependency on more central olfactory structures for the induction and maintenance of epileptiform activity in the olfactory bulb.

Animals↗
PubMed1992

Long-lasting excitation of protocerebral bilateral neurons in the pheromone-processing pathways of the male moth Bombyx mori.

Intracellular recording and staining with Lucifer yellow were used to characterize the responses and structure of pheromone-processing bilateral neurons in the protocerebrum of the brain of the male silkworm moth Bombyx mori. Numerous olfactory bilateral neurons innervated a particular neuropil region lateral to the central body, the lateral accessory lobe (LAL). The LALs are linked to each other by bilateral neurons with arborizations in each LAL. The LAL appears to be important for collecting the olfactory information from both sides of the brain. Many of the bilateral neurons showed a characteristic long-lasting excitation (LLE) that outlasted the olfactory stimuli (1.5 s). In some preparations, the LLE lasted more than 20 s and the firing gradually decreased to the background level.

Animals↗
PubMed1980

Double and triple labeling of neurons with fluorescent substances; the study of collateral pathways in the ascending raphe system.

A retrograde labeling procedure utilizing fluorescent substances (Granular Blue, Nuclear Yellow and propidium iodide) was used to establish the presence of branching axons in the ascending raphe system of young rats. After injections in septum, medial thalamus and olfactory cortex, the number of double-labeled cells in various combinations was found to be relatively large in the dorsal raphe nucleus, whereas triple-labeled cells occurred more rarely. Each class of neurons, i.e. single-, double- and triple-labeled, were shown to have a predominant distribution within specific parts of the nucleus.

Animals↗
PubMed1994

Intrabulbar associational system in the rat olfactory bulb comprises cholecystokinin-containing tufted cells that synapse onto the dendrites of GABAergic granule cells.

The intrabulbar associational system (IAS) originates from tufted cells whose axons terminate in the internal plexiform layer (IPL) on the opposite side of the same olfactory bulb. The postsynaptic targets of the IAS are unknown. Subpopulations of tufted cells contain different neuropeptides and transmitters but it is not known if tufted cells forming the IAS are homogeneous with respect to neurotransmitters. Therefore, the goals of the present study were to identify the postsynaptic targets of the IAS and to determine the major transmitter in this intrabulbar circuit. Biocytin anterograde tracing revealed that the axons of superficially situated tufted cells coursed directly to the IPL where they turned abruptly to run ventrally and dorsally to terminate in the IPL on the opposite side of the olfactory bulb. WGAapoHRP-Au retrograde tracing combined with immunohistochemistry for CCK revealed that all tufted cells retrogradely labeled by WGAapoHRP-Au injection in the IPL were immunoreactive for CCK. Anterograde transport of biocytin combined with postembedding immunocytochemical gold-labeling for GABA demonstrated that labeled IAS axons terminate predominantly, if not exclusively, on GABAergic granule cell dendrites in the IPL. These results confirm that the IAS arises from tufted cells and is topographically organized. We further demonstrate that tufted cells forming the IAS use the neuropeptide CCK as a transmitter. In addition, we show that the postsynaptic targets of the CCKergic IAS are the dendrites of GABAergic granule cells coursing through the IPL toward the EPL. As CCK is generally an excitatory neuropeptide, we suggest that the IAS functions to excite topographically discrete populations of granule cells. This action may lead to inhibition of equally discrete populations of mitral/tufted cells. Thus, the IAS may be an intrabulbar inhibitory circuit that coordinates topographically organized neural networks in the olfactory bulb.

Animals↗
PubMed1994

Neuroanatomical pathways linking vision and olfaction in mammals.

Retinal projections to several telencephalic structures have been demonstrated in a wide range of mammalian species following intraocular injections of tritiated amino acids and cholera toxin subunit-B conjugated to horseradish peroxidase. Since these regions are also innervated by olfactory fibers, we investigated the distribution of convergent projections using simultaneous injections of different anterograde tracers in the eye and olfactory bulbs. Convergent projections from the retina and from the olfactory bulbs were observed in the piriform cortex, olfactory tubercle, the cortical region of the medial amygdala, lateral hypothalamus, and the bed nucleus of the stria terminalis. A few retinal fibers also invade the nucleus of the lateral olfactory tract, the bed nucleus of the accessory olfactory bulb and the diagonal band of Broca. Injections of retrograde tracers in the medial amygdala, the bed nucleus or the lateral hypothalamus shows that the visuo-olfactory convergence mainly involves projections originating from the accessory olfactory bulb, and to a lesser extent from the ventromedial region of the main olfactory bulb. Fewer than 20 retinotelencephalic ganglion cells were identified in the retina, mainly located contralateral to the injection site. Ganglion cells were medium sized and possessed two long slender opposing dendrites. These retinal and olfactory projections could provide an anatomical substrate for the modulation of gonadotropin hormone levels and the olfactory influence on light mediated rhythms related to reproductive physiology.

Animals↗
PubMed1993

Morphological and quantitative evaluation of olfactory bulb development in Xenopus after olfactory placode transplantation.

We found previously that the number of olfactory axons is correlated with the number of mitral/tufted cells (output neurons of the olfactory bulb) during normal larval development. To examine the significance of this quantitative relationship, we evaluated the effects of transplanting an extra olfactory placode on the development of the larval olfactory bulb. We found that the transplanted tissue retained the normal, pseudostratified, columnar appearance and had the same cell types as normal olfactory epithelium, and the olfactory bulbs had the same laminar organization as control bulbs. With gross examination of the olfactory bulb, the side innervated by the transplant appeared slightly larger than the contralateral side in animals analyzed at a young larval stage (stage 50) and in 2 of the 9 animals examined at late larval stages (57/58). Tissue sections and area measurements, however, revealed that the volume of the olfactory bulbs in animals with a transplant was not significantly different from control values. Our quantitative analysis also showed that in stage-50 animals with a transplant, the total number of olfactory axons (in nerves from the transplanted and host olfactory organs) appeared to be greater than in control animals, but not to a statistically significant level. The number of mitral/tufted cells was not different from controls. In animals examined at stage 57/58, there was no difference from controls in either the total number of olfactory axons, total number of mitral/tufted cells, or convergence ratio of olfactory axons onto mitral/tufted cells. Thus, in the late-stage larvae, the quantitative relationship between olfactory axons and mitral/tufted cells was not altered by the experimental manipulation. These results suggest that the olfactory bulb can regulate the number of afferent fibers.

Animals↗