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Bilateral lesions of the bed nucleus of the accessory olfactory tract facilitate maternal behavior in virgin female rats.

In this study the effects of electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) on the induction of maternal behavior in virgin female Wistar rats was investigated. Results demonstrate a functional role of the BOAT in the neural control of maternal behavior in virgin female rats since bilaterally BOAT lesioned (BL) animals showed significantly shorter sensitization latencies (BL = 6 days) than sham lesioned (SH = 12 days) and intact control (C = 12 days) female rats. At the same time, statistically significant differences were observed in retrieval latency between BL (5.5 days) and C (10 days) groups, but not in the SH group (8 days). In physical contact frequency, the BL group reached higher scores than SH or C group. However, bilateral BAOT lesions failed to affect other maternal patterns such as nest building quality. Thus these results indicate that the BOAT, a vomeronasal system structure, is involved in the control of maternal behavior and that BL electrolytic lesions facilitate the onset of this behavior in virgin female Wistar rats.

Amygdala↗

Vomeronasal and/or olfactory mediation of ultrasonic calling and scent marking by female golden hamsters.

The role of the olfactory and vomeronasal systems in mediating odor-stimulated ultrasonic calling, flank marking, and vaginal marking by female hamsters was investigated by selective lesions of either system. Removal of the vomeronasal organ resulted in reduced frequencies of ultrasonic calling by estrous and nonestrous females in response to conspecific odors but it had no influence on either scent marking behavior during the same tests. When tested immediately after separation from a male, ultrasonic calling was not reduced by vomeronasal removal, indicating that such surgery does not cause deficits in calling ability and that the vomeronasal organ specifically mediates odor-stimulated calling. Zinc sulfate treatment of the olfactory mucosa led to reduction in the frequency of ultrasonic calling, flank marking, and vaginal marking in response to conspecific odors. Females' ability to discover buried food was also impaired by this treatment. Thus, the stimulation of both scent marking behaviors due to the perception of conspecific odors appears to be mediated primarily by the olfactory system, whereas stimulation of ultrasonic calling is mediated by both olfactory and vomeronasal systems.

Animals↗

Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior.

A modified method of applying ZnSO4 to the olfactory mucosa is described. Treated rats experienced severe nasal congestion that cleared within 24 h; more persistent morbidity did not occur. Nonpregnant females observed with male intruders 24 h following ZnSO4 showed no alterations in behavior other than a reduction in anogenital sniffing, indicating that they were not hypoactive or irritable. In other experiments, lactating females were observed in a hole-board apparatus; 2 days posttreatment anosmia was confirmed in 80% of bilaterally ZnSO4-treated females by the absence of preference for pup odors. After bilateral but not unilateral ZnSO4 treatment, initially activity scores and nose pokes were equivalent in all groups, but later they both were lower than in controls, probably due to a more rapid habituation to the novel apparatus. We conclude that intranasal ZnSO4 by small-volume spray is a useful experimental tool.

Administration, Intranasal↗

Pathways linking the olfactory bulbs with the medial preoptic anterior hypothalamus are important for intermale aggression in mice.

Manipulations affecting olfaction, as well as bilateral lesions of the medial preoptic anterior hypothalamic (MPAH) continuum, decrease intermale aggression in mice. In the present study, unilateral removal of an olfactory bulb was combined with a contralateral lesion of the MPAH. This surgery, like bulbectomy and bilateral lesions of the MPAH, substantially decreased aggressive behavior. This surgery bilaterally destroys the ipsilateral links between the olfactory bulbs and the MPAH, and it is this disruption that presumably causes the decrease in aggression. The effect is not due to removal of an olfactory bulb combined with hypothalamic damage per se, because ipsilaterally lesioned/bulbectomized males continued to fight without decrement after surgery. These results provide compelling evidence that multisynaptic neural pathways linking the chemosensory systems of the olfactory bulbs with the rostral hypothalamus are involved in the regulation of intermale aggression in mice.

Aggression↗

Hormonal and behavioral responses of male hamsters to females and female odors: roles of olfaction, the vomeronasal system, and sexual experience.

Removal of the vomeronasal organ eliminated androgen surges in male hamsters in response to female vaginal secretions in both sexually experienced and sexually naive males; lesions of the olfactory mucosa had no effect on such responses. Both lesions led to deficits in behavioral responses to vaginal secretions. In response to interactions with estrous females, in contrast, lesions of either system alone had no influence on androgen surges in males (either sexually experienced or naive). Lesions of both systems, however, eliminated androgen surges in sexually naive males but not sexually experienced males. These dual lesions eliminated male mating behavior, while lesions of either system alone had little influence on mating. There were no significant correlations in any experiment between level of behavioral responses and degree of change in androgen levels. Thus, we conclude that the vomeronasal system mediates androgen surges in response to female odors but is not necessary for such responses to females themselves. In sexually naive males the vomeronasal and olfactory systems together are necessary for androgen responses to females. Behavioral responses were influenced by lesions and by sexual experience. Lesions of both systems increased the latency to investigate vaginal secretions, and sexual experience decreased the latency and increased the duration of investigation. Lesions and experience also influenced male sexual performance.

Androgens↗

Anterior interhemispheric approach to aneurysms of the anterior communicating artery.

A modified anterior interhemispheric approach for clipping aneurysms of the anterior communicating artery is described. This approach is preferred on anatomical grounds because the anterior circle of Willis can be fully visualized with minimal manipulation of the frontal lobes and anterior cerebral arteries. The advantages of this approach are minimal traction, reduced operative time, and preservation of the olfactory nerve.

Humans↗

Influence of temperature on slow flow in populations of regenerating axons with different elongation velocities.

The slow intra-axonal transport mechanisms may be subdivided into 4 elementary processes: (a) protein synthesis; (b) release of the slow material from the cell body; (c) transport of the molecules along the axon; and (d) deposition of the material from the moving phase into the immobile axonal constituents. These 4 components of the slow flow mechanisms are differently affected by temperature and react differently to axonal regeneration. They have been studied at temperatures ranging from 10 to 35 degrees C, in 3 different populations of regenerating C-fibers of the garfish olfactory nerve. These 3 classes of axons have very different elongation properties as determined by elongation rates ranging from a minimum of 0.3 mm/day at 14 degrees C to a maximum of 12.4 mm/day at 35 degrees C. From this study several properties of the slow intra-axonal transport mechanism can be underlined: (a) in regenerating nerves the rate of slow flow is multiplied by a factor of 3.3 as compared to the rate characteristic of an intact nerve. A similar increase was measured in every regenerating phase regardless of the specific elongation velocity of the growing axons. This accelerated rate of slow flow has been measured previously in degenerating axons detached from their perikarya: therefore the rate increase appears to be triggered by the injury rather than the needs of the neuron; (b) protein synthesis represents one of the main steps controlling axonal elongation. Neurons with the most active level of protein synthesis grow with the highest elongation velocity; (c) the somal releasing times decrease exponentially with temperature but are identical to the values measured in intact neurons; (d) finally the height of the slow flow peak decreases exponentially as a function of the distance, as seen previously in intact nerves, but a significantly larger amount of radioactivity reaches the end of the nerve. It can be concluded that slow flow is intimately linked with the regeneration process. The rate of slow flow and more specifically of Scb represents the upper limit that can be reached by the elongation velocities of regenerating fibers when all the growth conditions are maximal. When the regenerating conditions are not at their peak, the axonal elongation proceeds at velocities which can be very significantly slower than the rate of slow flow and might be determined by the level of protein synthesis in the perikarya. Axonal elongation, however, can never proceed at a rate faster than slow flow.

Animals↗

Slow flow in regenerating C-fibers.

An identical rate of slow flow was measured in 3 different populations of regenerating C-fibers which have very different growth abilities as expressed by a 6-fold difference in their elongation velocities. At 21 degrees C, this rate of slow flow is 3.5 times faster than the rate measured in intact nerves and is identical to the elongation velocity of the most rapidly regenerating fibers. Slow flow may constitute the upper limit of the elongation velocity of a regenerating axon but other factors determined by the perikaryon (such as protein synthesis) might prevent the neuron from reaching the maximal growth rate.

Animals↗

Transmission and integration of biologically meaningful olfactory information after bilateral transection of the lateral olfactory tract in the rat.

The contribution of the olfactory inputs conveyed by the lateral olfactory tract (LOT) to the central olfactory areas in the onset of behavioral and electrophysiological responses i.e. multiunit activity of mitral cells was studied in rats which were submitted to a bilateral transection of LOT. The characteristic emotional reactions elicited in sham-operated rats by biologically meaningful odorants--odors of predator or of conspecific--were no longer observed after such lesion. At the olfactory bulb level, the differential habituation of mitral cell electrical responses according to the biological meaning of the stimuli disappeared in the rats with a bilateral section of LOT. However the awaking influence of the odorants when stimulations occurred during slow wave sleep remained unchanged: all the rats were more often awakened by the odor of predator than by the other stimuli. On the other hand, an inhibitory centrifugal influence of LOT on mitral cell electrical responses was noted in rats with a unilateral transection of LOT. The results are discussed in relation to the two olfactory pathways (lateral and medial). During wakefulness, LOT seems essential to the olfactory information processing; in slow wave sleep, the medial olfactory pathways appear to mediate olfactory discrimination and to elicit adapted arousal.

Animals↗

The role of the medial olfactory pathways in olfaction: behavioral and electrophysiological data.

The role of the olfactory inputs transmitted by the medial olfactory pathways --i.e. anterior limb of the anterior commissure and medial forebrain bundle-was studied in rats submitted either to a bilateral lesion of the anterior commissure (bAC group) or to a bilateral transection of the lateral olfactory tract followed by an anterior commissure bilateral lesion (bCL group). In the bCL group, the characteristic emotional reactions usually observed in sham-operated rats to biologically meaningful odorants (odor of a predator or of conspecifics) were no longer observed; in this group, the modulation of mitral cell electrical responses according to the biological meaning of the stimuli disappeared and no habituation was noted when the stimulations were repeated: few responses appeared at random; lastly, all the stimuli tested, the odor of conspecifics excepted, did not exert an awaking influence on the sleeping rats (slow wave sleep). On the contrary, emotional reactions were always observed in the bAC group, a slight increase of reactivity to the odorants was even noted. In this group of animals, the anterior commissure bilateral lesion induced a large increase of the bulbar responses to all the odorants; the habituation of the electrical responses disappeared, a large percentage of responses being always noted even for the tenth series of stimulation; these results point out the great inhibitory influence that the anterior commissure exerts on the olfactory bulb activity. In these bAC rats almost usual awaking influences were noted, however, the odor of conspecifics became as efficient as fox odor to awake the animals. Results are discussed in relation to the functional role of the medial and lateral olfactory pathways, the integrity of both the pathways being necessary for an accurate olfactory process.

Animals↗

Expression of platelet-derived growth factor B-chain in the mature rat brain and pituitary gland.

For better understanding of the role of platelet-derived growth factor (PDGF) B-chain in the brain, the expression of PDGF B-chain was studied in the mature rat brain at both protein and mRNA levels, by assay of PDGF B-chain-related mitogenic activity, Northern blot, in situ hybridization and immunohistochemistry. It was shown that (1) mature rat brain contained substantial PDGF B-chain-related mitogenic activity, (2) significant amounts of two sizes of transcripts (3.5 kb, widely, and 2.6 kb, weakly and in narrower areas) were expressed in the brain, and (3) the transcripts were localized in ubiquitous neurons by in situ hybridization, with the strongest signal in hippocampal pyramidal cells, which distribution almost corresponded with that of the immunoreactive products. The abundant neuronal localization of the transcript and protein, as well as the neuronal expression of the receptor reported elsewhere, suggests the role of the growth factor in neuronal cells as a neuronal regulatory and/or trophic agent acting by autocrine loop or by neuron to neuron interaction. However, there was an apparent discrepancy in part, in the distribution between transcripts and immunoreactivity; that is, transcripts were expressed intensely in the intermediate pituitary lobe with only a scattered immunoreactivity, and the opposite situation was observed in the accessory olfactory nerve and posterior pituitary lobe. This might suggest that PDGF B-chain is transported or secreted in these foci.

Animals↗

Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system.

A specific form of cytochrome P450, P450 IIE1, active in ethanol oxidation, is known to be induced about 10-fold in rat liver following ethanol treatment. This isozyme of P450 participates effectively in the metabolic activation of precarcinogens, such as N-dimethylnitrosamines, and of solvents such as carbon tetrachloride and benzene. In the present investigation, two different polyclonal antisera against P450 IIE1 were used in order to map the regional distribution of this P450 form in the rat central nervous system. The presence of P450 IIE1 in various brain regions was confirmed by Western blot analysis. The P450 IIE1-immunoreactivity was heterogeneously distributed between brain areas. Neuronal cell bodies and glial cells of presumed astroglial as well as oligodendroglial identity contained immunoreactivity. All fiber tracts harbored P450 IIE1-immunoreactive glial cells as did the ependymal lining of the ventricular wall as well as small and large vessels throughout the brain. P450 IIE1-immunoreactive glial cells were present in all areas of the neocortex, in the olfactory bulb, in the piriform cortex and in several different thalamic nuclei. In the cerebellum, P450 IIE-immunoreactivity was found in all cell layers and was exclusively localized to glial cells and their processes. Staining of blood vessels was prominent in the white matter where P450 IIE1-immunoreactive glial cells were seen to have end-feet on the vessels. A subgroup of pyramidal cells of the frontal cortex showed strong P450 IIE1-immunoreactivity, as did a component of the olfactory nerve which innervates the accessory bulb. In the hippocampal region, the pyramidal cells of all subfields were P450 IIE1-immunoreactive. Some polymorphic cells of the hilus and subfield CA stained intensely with the P450 IIE1 antibodies. A high density of P450 IIE1-immunoreactivity was detected throughout the striatal complex. The immunoreactivity was localized to neuronal cell bodies as well as the neurophil. Fibers of the nigrostriatal system were strongly P450 IIE1-immunoreactive. Mechanical lesions of this pathway showed an accumulation of P450 IIE1-immunoreactivity proximal to the lesion relative to the striatum and a depletion in the reticular part of the substantia nigra, suggesting that the antigen may be transported from the striatum to the substantia nigra. In the brain stem a high density of P450 IIE-immunoreactive neurons was detected in the substantia nigra, the pontine nucleus, lateral superior olive and the nucleus of the trigeminal nerve and facial nucleus. A great number of large- to medium-sized immunoreactive neurons were situated in the central gray and in the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hypothalmic influences on the electrical activity of the olfactory pathway.

By means of evoked potentials a direct efferent connection was found to run from the posterior hypothalmus and medial forebrain bundle to primary olfactory structures (olfactory bulb, olfactory tubercle and prepyriform cortex). The pathway from the hypothalmus to the olfactory bulb follows in the lateral olfactory tract at a conduction velocity 5-10 m/sec. The olfactory tubercle functions as a relay station for the efferent fibers from various sources, running to the olfactory bulb. In animals with electrodes chronically implanted in the olfactory structures, hypothalamic stimulation gives rise to a prolonged train of hypersynchronous bursts of activity (40-50 Hz), which resemble the arousal reaction. This response is modified by transecting the cervical sympathetic trunk. By pathways still to be defined, potentials are evoked in the olfactory bulb by stimulation of the cervical sympathetic trunk and the termination of these sympathetic fibers shows a common postsynaptic neuronal pool with axons of hyopothalmic origin. Epinephrine topically applied to the olfactory mucosa induced hypersynchronous activity in olfactory structures, quite similar to that consequent to hypothalmic stimulation. These results suggest a multichanneled hypothalmic modulation of olfactory input.

Animals↗

Transport of molecules from nose to brain: transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium.

Transneuronal anterograde labeling with the conjugate wheat germ agglutinin-horseradish peroxidase (WGA-HRP) has been documented in the mammalian and immature avian visual system [6,14]. Transneuronal retrograde labeling was significant only in the chick [6]. The present study was performed to determine whether transneuronal labeling could be shown in the mammalian olfactory system, whether the phenomenon was robust in adults, and whether transneuronal retrograde transport could label several transmitter-specific centrifugal afferent projections to the olfactory bulb. In addition we wished to learn whether molecules that enter the nasal cavity can undergo transport to brain neurons. Gelfoam implants soaked with 1% WGA-HRP, surgically implanted into the nasal cavity, produced transneuronal labeling patterns that affirmed all of these questions. Transneuronal anterograde transport labeled the appropriate zones in the olfactory bulb and in all second order olfactory targets. In addition, there was transneuronal retrograde labeling of neurons in the olfactory bulb, anterior olfactory nucleus and in transmitter-specific projection neurons from the diagonal band (cholinergic), raphe (serotonergic) and locus coeruleus (noradrenergic). Transneuronal labeling was robust and consistent. The patterns of labeling indicated that transneuronal anterograde and retrograde transport occurred along known, specific circuits in the olfactory system. The present results suggest that nasal epithelial application of WGA-HRP may be a useful tool for assessing regeneration of primary olfactory neurons and the status of central circuitry following regeneration. The method should also facilitate the study of central olfactory connections after surgical or genetic lesions of the olfactory bulb. Finally, these experiments suggest the possibility that inhaled molecules including, possibly substances of abuse, may be transported to, and, possibly, influence the function of neurons in the brain, including some (diagonal band, raphe, locus coeruleus) which have extensive projections to wide areas of the CNS.

Animals↗

Current generators and properties of early components evoked in rat olfactory cortex.

Depth-profile, current-source-density (CSD) and impedance analysis were used to determine the current generators of secondary waves "a" and "b" in the response evoked in pyriform cortex (PC) of the urethane anesthetized rat following OB or LOT stimulation. Positive peaks (sinks) in the second-derivative curves of the "a" and "b" waves were localized at 50-75 and 225-250 microns deep, respectively. Cortical impedance was significantly (p less than 0.01) correlated with the cell packing density of PC layers, being maximal close to the zero dipole point of the gross evoked response; magnitude of conductivity gradients was, however, insufficient to alter the interpretation of positive and negative peaks in terms of net membrane currents. Post-tetanic and/or frequency potentiation of PC responses but not long-term potentiation were found in the majority of animals tested. Recovery of the test "b" wave was faster when using paired-shock stimulation at 3.0 Hz than at 0.3 Hz; suppression of this component following a conditioning OB volley could be overcome and the "b" wave facilitated if either a long-latency component (i.e., 65-100 msec) was present in the priming response, or if the conditioning stimulus was delivered to the mediodorsal thalamic nucleus (MDT). These results confirm and extend similar ones in other species, suggesting that following OB or LOT stimulation three successive excitatory processes take place in PC neural elements of the rat under urethane anesthesia: an initial monosynaptic excitation of distal segments of apical dendrites of layer II cells, and to a lesser extent, also of layer III neurons ("a" wave), followed by action potentials in their respective somas (PS wave); subsequently, long association axons give rise to a di or polysynaptic compound EPSP in proximal apical and possibly also, in basal pyramidal dendrites ("b" wave; early reactivation process). Finally, a "late" reactivation takes place in PC involving neurons which participated in the early reactivation process (late component). In addition, heterosynaptic facilitation of the "b" wave in the PC evoked response follows MDT conditioning stimulation.

Animals↗

Identification of immunoreactive mammalian gonadotropin-releasing hormone in the brain of metamorphic larvae of Bufo arenarum Hensel (Amphibia: Anura).

Gonadotropin-releasing hormone (GnRH) immunoreactivity in brain extracts of Bufo arenarum tadpoles were investigated by high-performance liquid chromatography, followed by radioimmunoassay analysis using two different antisera raised against different GnRH variants. Only one immunoreactive peak was identified, eluting in the same position as synthetic mammalian GnRH. This result was further confirmed by serial dilution studies using more specific mammalian GnRH antisera. Our results suggest that mammalian GnRH is most likely an endogenous peptide in the brain of the developing larvae and froglets of Bufo arenarum and quite likely it is the only GnRH variant present during those development stages. The distribution and density of cell bodies and fibers were analysed by immunocytochemical procedures. Immunoreactive cell bodies appeared in the olfactory epithelium and across the olfactory nerve at late prometamorphic larval stages. Near the metamorphic climax and in froglets, perikarya and fibers were detected in basal forebrain, preoptic and hypothalamic areas. No immunoreaction was observed at midbrain, hindbrain and spinal cord levels. This study suggests that mammalian GnRH is most likely an endogenous peptide and is probably the only GnRH variant in the brain of the developing larvae and froglets of Bufo arenarum.

Animals↗

Biodegradable mucoadhesive particulates for nasal and pulmonary antigen and DNA delivery.

Biodegradable polymer and particulate carriers have been shown to be of considerable potential for the delivery of peptides, proteins and DNA in animal models. In the context of vaccine delivery to the upper and lower respiratory tracts, the use of mucoadhesive agents offers a strategy for the facilitation of increased residence time and increased vaccine efficacy. Additional concerns addressed here include the potential of uptake of vaccine formulations by the primary olfactory nerves in the nasal cavity, effective delivery to the lung, strategies to maximise the immunopotentiation of candidate vaccine formulations, as well as the evaluation of animal models and interpretation of engendered immune responses in terms of antigen-specific antibody production. Experimental data are presented that demonstrate the potential of muco- and bioadhesive agents in combination with liposomes for intranasal (i.n.) delivery of tetanus toxoid in mice. A delivery system utilising chitosan for the formulation of microspheres by the spray-drying method is described and assessed for intranasal vaccine delivery, and porous particles with potential for pulmonary administration are also outlined.

Administration, Intranasal↗