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PubMed2007

Temporal target restriction of olfactory receptor neurons by Semaphorin-1a/PlexinA-mediated axon-axon interactions.

Axon-axon interactions have been implicated in neural circuit assembly, but the underlying mechanisms are poorly understood. Here, we show that in the Drosophila antennal lobe, early-arriving axons of olfactory receptor neurons (ORNs) from the antenna are required for the proper targeting of late-arriving ORN axons from the maxillary palp (MP). Semaphorin-1a is required for targeting of all MP but only half of the antennal ORN classes examined. Sema-1a acts nonautonomously to control ORN axon-axon interactions, in contrast to its cell-autonomous function in olfactory projection neurons. Phenotypic and genetic interaction analyses implicate PlexinA as the Sema-1a receptor in ORN targeting. Sema-1a on antennal ORN axons is required for correct targeting of MP axons within the antennal lobe, while interactions amongst MP axons facilitate their entry into the antennal lobe. We propose that Sema-1a/PlexinA-mediated repulsion provides a mechanism by which early-arriving ORN axons constrain the target choices of late-arriving axons.

Animals↗

PubMed2005

Impaired male sexual behavior in activin receptor type II knockout mice.

Integration of multiple hormonal and neuronal signaling pathways in the medial preoptic area (mPOA) is required for elicitation of male sexual behavior in most vertebrates. Perturbation of nitric oxide synthase (NOS) activity in the mPOA causes significant defects in male sexual behavior. Although activins and their signaling components are highly expressed throughout the brain, including the mPOA, their functional significance in the central nervous system (CNS) is unknown. Here, we demonstrate a neurophysiologic role for activin signaling in male reproductive behavior. Adult activin receptor type II null (Acvr2-/-) male mice display multiple reproductive behavioral deficits, including delayed initiation of copulation, reduced mount, and intromission frequencies, and increased mount, intromission, and ejaculation latencies. These behavioral defects in the adult mice are independent of gonadotropin-releasing hormone (GnRH) homeostasis or mating-induced changes in luteinizing hormone (LH) and testosterone levels. The impairment in behavior can be correlated to the nitric oxide content in the CNS because Acvr2-/- males have decreased NOS activity in the mPOA but not the rest of the hypothalamus or cortex. Olfactory acuity tests confirmed that Acvr2-/- mice have no defects in general odor or pheromone recognition. In addition, motor functions are not impaired and the mutants demonstrate normal neuromuscular coordination and balance. Furthermore, the penile histology in mutant mice appears normal, with no significant differences in the expression of penile differentiation marker genes compared with controls, suggesting the observed behavioral phenotypes are not due to structural defects in the penis. Our studies identify a previously unrecognized role of activin signaling in male sexual behavior and suggest that activins and/or related family members are upstream regulators of NOS activity within the mPOA of the forebrain.

Activin Receptors, Type II↗

PubMed1993

Convergence of olfactory and nasotrigeminal inputs and possible trigeminal contributions to olfactory responses in the rat thalamus.

To elucidate the role of trigeminal input on the olfactory system, field-evoked potentials were measured following electrical stimulation of the nasociliary branch of the trigeminal nerve in the olfactory-related structures in the rat brain. Significant potential changes were recorded in the mediodorsal nucleus of the thalamus and the lateral hypothalamic area. In the mediodorsal nucleus of the thalamus, the neurons responding to olfactory bulb electrical stimulation also responded to trigeminal nerve stimulation. Single neuronal responses of mediodorsal thalamic neurons following odorant stimulation were enhanced by blockade of the trigeminal nerve with procaine. These results suggest that olfactory and trigeminal pathways converge on the same neural elements within the mediodorsal nucleus of the thalamus and that the trigeminal input may modulate olfactory input in this nucleus.

Animals↗

PubMed2003

Cortical and striatal expression of tyrosine hydroxylase mRNA in neonatal and adult mice.

1. Elucidating the mechanisms underlying regulation of the dopamine (DA) phenotype during development and in adult animals was a major focus of many of the students and postdoctoral fellows in the Laboratory of Dr Donald Reis. In one series of studies, expression of tyrosine hydroxylase (TH), the first enzyme in the DA biosynthetic pathway, was induced in primary cultures prepared from the cortical anlage of embryonic day 13 (E13)-E17 rat embryos. On the basis of these data, the current studies investigated whether under appropriate conditions TH expression might occur in forebrain regions that do not normally contain DA neurons. 2. A transgenic mouse strain harboring a 9-kb TH promoter/EGFP (enhanced green fluorescent protein) reporter construct was analyzed as adults for coexpression of the fluorescent reporter and the endogenous gene, the latter using a sensitive nonradioactive in situ hybridization procedure. The latter procedure was also used to determine the development of neonatal cortical endogenous TH expression. 3. Cortical and striatal cells containing TH mRNA were observed at postnatal day 5 (P5), but not P2, increased in number at P7 and were found in adults. Many cells in the cortex and striatum coexpressed TH mRNA and EGFP, but TH protein was not detected in these brain regions indicating independent transcriptional and translational regulation of TH expression. Overlapping expression of the two transcriptional indicators and TH protein in olfactory bulb occurred only in those DA neurons that receive afferent stimulation from receptor cells. 4. These findings suggest that partial DAergic differentiation may occur in some cortical and striatal cells, but that full expression of the phenotype requires synaptic activation or activity-dependent release of an as-yet unidentified factor(s).

Animals↗

PubMed2001

Glucagon-like immunoreactivity in the forebrain and pituitary of the teleost, Clarias batrachus (Linn.).

The organization of glucagon-like immunoreactivity (GLI) in the olfactory system, forebrain, and pituitary was investigated in the teleost Clarias batrachus. Weak to moderate GLI was seen in some olfactory receptor neurons and basal cells of the olfactory epithelium. Intense GLI was seen in the olfactory nerve fascicles that ran caudally to the bulb, spread over in the olfactory nerve layer, and profusely branched in the glomerular layer to form tufts organized as spherical neuropils; some of the immunoreactive fibers seem to closely enfold the mitral cells. In the inner cell layer of the bulb, some granule cells were intensely immunoreactive. Although there were thick fascicles of immunoreactive fibers in the medial olfactory tracts (MOT), the lateral olfactory tracts were generally devoid of immunoreactivity. Immunoreactive fibers in the medial olfactory tract penetrated into the telencephalon from its rostral pole and entered into the area ventralis telencephali/pars ventralis where the compact fiber bundles loosen somewhat and course dorsocaudally into the area ventralis telencephali/pars supracommissuralis just above the anterior commissure. While some immunoreactive fibers decussated in the anterior commissure, fine fibers were seen in the commissure of Goldstein. Isolated immunoreactive fibers of the medial olfactory tract were traced laterally into the area dorsalis telencephali/pars lateralis ventralis and mediodorsally into the area dorsalis telencephali/pars medialis. However, a major component of the MOT continued dorsocaudally into the thalamus and terminated in the habenula. Two immunoreactive neuronal groups and some isolated cells were seen in the periventricular region of the thalamus. Although nucleus preopticus showed no immunoreactivity, some neurons of the nucleus lateralis tuberis displayed moderate GLI. Several immunoreactive cells were seen in the pars intermedia of the pituitary gland; few were encountered in the rostral pars distalis and proximal pars distalis. Immunoreactive fibers were seen throughout the pituitary gland.

Animals↗

PubMed1992

Mating behavior induces selective expression of Fos protein within the chemosensory pathways of the male Syrian hamster brain.

The effect of mating behavior on the expression of Fos protein was analyzed within the chemosensory pathways of the male Syrian hamster brain. Following a single mating test, the number of Fos-immunoreactive (Fos-ir) neurons increased within the amygdala, bed nucleus of the stria terminalis and medial preoptic area. The mating-induced pattern of Fos expression within these brain regions shows a strong correlation with the sites of lesions that eliminate or alter mating behavior. In addition, Fos expression was increased within the paraventricular nucleus of the hypothalamus. These results provide the first demonstration of a dynamic and selective pattern of neuronal activity within specific nuclei known to be essential for mating behavior in the male Syrian hamster.

Amygdala↗

PubMed1985

Topographic organization of tufted cell axonal projections in the hamster main olfactory bulb: an intrabulbar associational system.

The organization of intrinsic axonal projections of principal neurons in the main olfactory bulb (MOB) was studied in hamsters by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and fluorescent dyes. Punctate injections of either WGA-HRP or fast blue (FB) that are restricted to small sectors on one side of the MOB produce comparably restricted fields of retrograde labeling on the opposite side. Label is found predominantly in superficially situated (middle and external) tufted cells that lie near and at the border between the external plexiform and glomerular layers. Few of the deeper middle tufted, internal tufted, or mitral cells and no external tufted cells that lie in the superficial two-thirds of the glomerular layer are labeled in regions remote to the injection site. Anterograde transport of WGA-HRP from the injection site labels axons that travel dorsally and ventrally in restricted bands through the internal plexiform layer and then terminate within this layer in the punctate sector on the opposite side that contains retrogradely labeled neurons. Such reciprocal projections between opposing regions of the medial and lateral sides of the MOB are found at all rostrocaudal and dorsoventral levels. When punctate injections of FB into the MOB are paired with restricted injections of a second fluorescent tracer (nuclear yellow or diamidino yellow dihydrochloride) into the appropriate sector of pars externa (pE) of the anterior olfactory nucleus, the punctate region of remote retrogradely labeled principal neurons is embedded within a topographically restricted longitudinal wedge of retrogradely labeled mitral and tufted cells that project extrinsically to or through pE. However, extremely few of these neurons are double-retrogradely labeled. The results reveal the existence of an intrabulbar associational system in which principal neurons engage in point-to-point, reciprocal projections between opposing regions of the medial and lateral MOB. Moreover, the results indicate that this associational system largely arises from superficially situated tufted cells distinct from those that support bulbofugal projections into the topographically organized interbulbar commissural system via pE.

Animals↗

PubMed1985

Synaptic contacts of ventral striatal cells in the olfactory tubercle of the rat: correlated light and electron microscopy of anterogradely transported Phaseolus vulgaris-leucoagglutinin.

Iontophoretic injections of the plant lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into the dense cell layer of the rat olfactory tubercle (OT) resulted in transport of the substance to the polymorph layer of the OT. Light microscopy revealed that the lectin was taken up in the superficial OT exclusively by medium-sized neurons with spiny dendrites of which the majority extended into the molecular layer. PHA-L-immunoreactive elements were observed in the adjoining part of the polymorph layer in the form of filaments and puncta which the electron microscope revealed to be axons and boutons forming symmetrical synaptic contacts, almost exclusively with typical pallidal-type dendrite profiles. The results reinforce the concept that the medium-size cells of the dense cell layer of the OT represent the ventral-most part of the striatum.

Animals↗

PubMed2001

Parvalbumin-containing interneurons do not innervate granule cells in the olfactory bulb.

Combining pre-embedding parvalbumin immunostaining and post-embedding immunogold detection of GABA in the olfactory bulb, we investigated whether the parvalbumin-containing GABAergic interneurons of the external plexiform layer exclusively innervate principal cells, or whether they also establish inhibitory synapses upon GABAergic local neurons such as granule cells. Our results demonstrate that the parvalbumin-containing cells do not contact GABAergic interneurons in the neuropil of the external plexiform layer. On the contrary, their postsynaptic elements were always non-GABAergic principal cells. Although classically it has been accepted that the interneurons of the external plexiform layer could exert a disinhibitory action upon principal cells, via inhibition of GABAergic granule cells, we conclude that they exert a feedback inhibitory action directly and exclusively upon principal cells.

Animals↗

PubMedDate not supplied

Drosophila mushroom bodies are dispensable for visual, tactile, and motor learning.

A total of 18 associative learning/memory tests have been applied to Drosophila melanogaster flies lacking mushroom bodies. Only in paradigms involving chemosensory cues as conditioned stimuli have flies been found to be compromised by a block in the mushroom body pathway. Among the learning tasks not requiring these structures are a case of motor learning (yaw torque/heat), a test of the fly's spatial orientation in total darkness, conditioned courtship suppression by mated females, and nine different examples of visual learning. The latter used the reinforcers of heat, visual oscillations, mechanical shaking, or sucrose, and as conditioned stimuli, color, intensity contrast, as well as stationary and moving visual patterns. No forms of consolidated memory have been tested in mushroom body-less flies. With respect to short-term memory the mushroom bodies of Drosophila are specially required for chemosensory learning tasks, but not for associative learning and memory in general.

Animals↗

PubMed1987

Sources of presumptive glutamergic/aspartergic afferents to the rat ventral striatopallidal region.

The distribution of presumptive glutamergic and/or aspartergic neurons retrogradely labeled following injections of 3H-D-aspartate (3H-D-Asp) into the ventral striatopallidal region was compared with the distribution of neurons labeled by comparable injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The afferents labeled by 3H-D-Asp were a subset of those labeled by WGA-HRP. The major sources of afferents to the nucleus accumbens and olfactory tubercle that could be labeled by 3H-D-Asp were in the medial frontal and insular cortices; the olfactory cortex; the lateral, basolateral, and basomedial amygdaloid nuclei; and the midline nuclear complex of the thalamus. The corresponding afferents to the ventral pallidum arose in the central, medial, and basomedial amygdaloid nuclei and the midline thalamic nuclei. In addition, the nucleus of the lateral olfactory tract was moderately or heavily labeled by 3H-D-Asp injections into all three areas, and cells were labeled in the subiculum following injection in the anteromedial part of the nucleus accumbens. Conversely the ventral striatopallidal structures themselves were, at best, sparsely labeled by any of the 3H-D-Asp injections. Neurons in the substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus were labeled by WGA-HRP but not by 3H-D-Asp, except for an occasional cell in the raphe. The results indicate that 3H-D-Asp is a specific retrograde tracer and suggest that there are widespread, presumably excitatory, glutamergic and/or aspartergic inputs to the ventral striatum and pallidum.

Animals↗

PubMed2005

Hormonal and sensory inputs regulate distinct neuroblast cell cycle properties in adult cricket brain.

From invertebrates to humans, it has been demonstrated that new neurons are added to specific brain structures throughout adult life. In the house cricket, adult neurogenesis occurs in the mushroom bodies, the main sensory integrative center of the brain, often considered an analogue of vertebrate hippocampus. We have previously shown that this neurogenesis can be modulated by hormones through the polyamine pathway and by environmental conditions through sensory inputs and the nitric oxide pathway. Environment-induced neurogenesis is independent of juvenile hormone levels, so we addressed the roles of sensory inputs and hormones in the control of neuroblast proliferation. Here, by using double labelling of cells specifically in S phase (5-bromo-2'-deoxyuridine) together with labelling of mitotically active cells in any phase (proliferating cell nuclear antigen), we show that juvenile hormone acts on progenitor cell proliferation by inducing quiescent neuroblasts to enter the cell cycle, whereas sensory inputs act by shortening the cell cycle. Thus, in the adult house cricket, regulation of neuroblast proliferation by hormonal and environmental cues occurs through two independent modes of action.

Animals↗

PubMed1998

Bidirectional connections of the medial amygdaloid nucleus in the Syrian hamster brain: simultaneous anterograde and retrograde tract tracing.

In the male Syrian hamster, mating is dependent on chemosensory and hormonal stimuli, and interruption of either input prevents copulation. The medial amygdaloid nucleus (Me) is a key nodal point in the neural circuitry controlling male sexual behavior because it relays both odor and steroid cues. Me is comprised of two major subdivisions, anterior (MeA) and posterior (MeP), which have distinct, although overlapping efferent projections. The present study investigated the afferents and efferents of MeA and MeP by using combined anterograde and retrograde tract tracing. Phaseolus vulgaris-leucoagglutinin and cholera toxin B were injected by iontophoresis through a single glass micropipette and detected by immunohistochemistry. MeA has widespread connections with olfactory structures, whereas MeP is heavily interconnected with steroid-responsive brain regions. The efferent projections of MeA and MeP were similar to those reported previously for the rat and hamster. In particular, MeP projects to the posteromedial subdivision of the bed nucleus of the stria terminalis (BNST) and to the medial preoptic nucleus, whereas MeA projects to adjacent subnuclei in BNST and the preoptic area. MeA and MeP also have distinct patterns of afferent input. Furthermore, the combination of anterograde and retrograde tract tracers shows that MeA and MeP are each bidirectionally connected with each other and with limbic nuclei. These results demonstrate that subnuclei of Me are interconnected with limbic structures in hamster brain. These connections may contribute to chemosensory and hormonal integration to control male sexual behavior.

Amygdala↗

PubMed1988

Visceral cortex: integration of the mucosal senses with limbic information in the rat agranular insular cortex.

The organization of the subcortical and cortical connections of the rat agranular insular cortex was examined. Retrogradely transported dyes were used to map the agranular insular cortex efferents to brainstem visceral nuclei (the nucleus of the solitary tract and the parabrachial nucleus), to gustatory-visceral and limbic thalamic nuclei (medial ventrobasal and mediodorsal thalamus, respectively), and to association cortex (medial prefrontal and contralateral agranular insular cortex). The results revealed that a specific area within the ipsilateral agranular insular cortex projected to all of the subcortical and cortical areas listed above. This area of overlap in the agranular insular cortex stretched from the level of the genu of the corpus callosum rostrally to the crossing of the anterior commissure caudally. Anterograde projections from the medial ventrobasal and mediodorsal thalamus and from the olfactory bulb to the agranular insular cortex were mapped with wheat germ agglutinin conjugated to horseradish peroxidase. The terminal cortical projections from these areas were generally separate, except in an area where they overlap immediately medial to the rhinal fissure in the agranular insular cortex. This overlap area matched the area in the agranular insular cortex where there was an overlap of cortical efferent cells projecting to the brainstem, thalamus, and association cortex, as revealed in the retrograde tracing studies. We refer to this region of convergence in the agranular insular cortex as the visceral cortex, and suggest its involvement in the efficient integration of specific visceral sensory stimuli with correlated limbic or motivational consequences. The visceral cortex may help regulate the organism's visceral response to stress.

Animals↗

PubMed2002

Role of MAP kinase in signaling indispensable amino acid deficiency in the brain.

Deficiencies of indispensable amino acids (IAAs) appear to be sensed in the anterior piriform cortex (APC) where neurons are activated and potentiated, however, the mediating intracellular signaling mechanisms are largely unexplored. It is postulated that signaling of amino acid deficiency may share many of the same pathways seen with long-term potentiation (LTP). Phosphorylation of mitogen-activated protein kinase (pMAP kinase) has been shown to be a necessary signaling event for the genesis and maintenance of LTP. Immunoperoxidase immunohistochemistry was used to determine the number of neurons showing activation of the MAP kinase signal transduction system. Relative to rats eating a corrected diet, rats consuming threonine-devoid diet showed significantly greater pMAP kinase labeling in the APC, dorsomedial hypothalamus, and the paraventricular hypothalamic nucleus. These are areas previously associated with control of food intake. However, since the dorsomedial hypothalamus and the paraventricular hypothalamic nucleus have not previously been implicated as chemosensory areas for IAAs, phosphorylated MAP kinase expression in these areas may reflect secondary activation.

Animals↗

PubMed1983

Short-term potentiation phenomena in the rat limbic forebrain.

Several types of short-term postactivation potentiation (PAP) effect were examined in limbic forebrain pathways in the chronic rat. We tested 9 different stimulation sites and 1-3 target sites for each stimulation site. All pathways showed PAP effects following activation by single electrical pulses or pulse trains. Using exponential curve fitting procedures, we found that the decay curves could be best fitted by one, or a sum of 2-3, exponential curves. On the basis of time constants, these curves fell into 4 different categories: facilitation (tau = 80 ms), augmentation (tau = 7s), potentiation 1 (tau = 70s), and potentiation 2(tau = 6.5 min). The latter component was the one most reliably generated in the chronic preparation. Frequency facilitation (facilitation during a stimulation train) was also examined and it appeared to be based upon a mechanism similar to that underlying paired pulse facilitation. Evidence is presented that facilitation and augmentation may be based on the the same mechanism. The possibility that the remaining components involve different mechanisms is discussed.

Amygdala↗

PubMed1972

Neural associations of the frontal cortex.

Recent anatomical findings in the monkey indicate that the frontal cortex receives associative afferents from the visual, auditory, and somatosemsory areas of the cortex. The inferior parietal lobule and the inferior temporal cortex are important way-stations in these cortico-cortical afferent pathways. The olfactory system represents a fourth sensorium having access to the frontal cortex, namely, by way of substantial projections from the pirifom cortex and olfactory tubercle to the medial subdivision of the thalamic mediodorsal nucleus. Additional afferents to this nucleus originate from various fore- and midbrain structures implicated in the circuitry of the limbic system; such afferents could well be ediators of information related to the organism's internal milieu. On the efferent side, the frontal cortex is associated with the inferior parietal, temporal, cinguloparahippocampal cortex, and entorhinal area; it is the only cortical region known to project directly to the hypothalamus and hypothalamus-related structures in the paramedian midbrain tegmentum. The mosaic of origin and termination of the various connections indicates that the convexity of the frontal lobe (especially its caudal half) is reciprocally associated with the parietal and temporal cortex, while the major associations with the hippocampal mechanism originate from two separate areas, viz. the caudal orbitofrontal cortex and a region dorsal to the sulcus principalis, frontal fields from which also the major fronto-hypothalamic connections arise.

Animals↗

PubMed1986

Immunocytochemistry of GABA in the antennal lobes of the sphinx moth Manduca sexta.

We have prepared and characterized specific rabbit antisera against gamma-aminobutyric acid (GABA) coupled covalently to bovine serum albumin and keyhole-limpet hemocyanin. Using these antisera in immunocytochemical staining procedures, we have probed the antennal lobes and their afferent and efferent fiber tracts in the sphinx moth Manduca sexta for GABA-like immunoreactivity in order to map putatively GABAergic central neurons in the central antennal-sensory pathway. About 30% of the neuronal somata in the large lateral group of cell bodies in the antennal lobe are GABA-immunoreactive; cells in the medial and anterior groups of antennal-lobe cells did not exhibit GABA-like immunoreactivity. GABA-immunoreactive neurites had arborizations in all of the glomeruli in the antennal lobe. Double-labeling experiments involving tandem intracellular staining with Lucifer Yellow and immunocytochemical staining for GABA-like immunoreactivity demonstrated that at least some of the GABA-immunoreactive cells in the antennal lobe are amacrine local interneurons. Several fiber tracts that carry axons of antennal-lobe projection neurons exhibited GABA-immunoreactive fibers. Among the possibly GABA-containing projection neurons are several cells, with somata in the lateral group of the antennal lobe, that send their axons directly to the lateral protocerebrum.

Animals↗