Alan J Nighorn
- Department Head, Neuroscience
- University Distinguished Professor
- Professor, Neuroscience
- Professor, Molecular and Cellular Biology
- Professor, Entomology / Insect Science - GIDP
- Professor, Neuroscience - GIDP
- Professor, BIO5 Institute
- Ph.D. Cell Biology
- Baylor College of Medicine, Houston, Texas, United States
- University Distinguished Professor
- University of Arizona, Summer 2016
- 5 star faculty award finalist
- The honors college, Spring 2015 (Award Finalist)
- 5 Star Faculty Award Finalist
- Honors College, Spring 2013 (Award Finalist)
No activities entered.
Honors PreceptorshipNSCS 491H (Spring 2018)
Molecular/Cell Bio of NeuronsNROS 310 (Spring 2018)
PreceptorshipNSCS 491 (Spring 2018)
Special Topics in ScienceHNRS 195I (Spring 2018)
Cellular NeurophysiologyNROS 307 (Fall 2017)
Honors PreceptorshipNSCS 491H (Fall 2017)
Honors ThesisNSCS 498H (Fall 2017)
Methods in NeuroscienceNSCS 315B (Fall 2017)
Molecular Mech Learning/MemoryNROS 412 (Fall 2017)
PreceptorshipNSCS 491 (Fall 2017)
ThesisBIOC 910 (Summer I 2017)
Honors PreceptorshipNSCS 491H (Spring 2017)
Honors ThesisNSCS 498H (Spring 2017)
Molecular/Cell Bio of NeuronsNROS 310 (Spring 2017)
PreceptorshipNSCS 491 (Spring 2017)
Cellular NeurophysiologyNROS 307 (Fall 2016)
Honors PreceptorshipNSCS 491H (Fall 2016)
Honors ThesisNSCS 498H (Fall 2016)
Independent StudyNSCS 399 (Fall 2016)
Molecular Mech Learning/MemoryNROS 412 (Fall 2016)
PreceptorshipNSCS 491 (Fall 2016)
Special Topics in ScienceHNRS 195I (Fall 2016)
ResearchBIOC 900 (Summer I 2016)
- Gage, S., & Nighorn, A. (2014). The role of nitric oxide in memory is modulated by diurnal time. Front Syst Neurosci, 8, 59.More infoDate: 04/11/2014; doi: 10.3389/fnsys.2014.00059
- Dacks, A. M., Reale, V., Yeli, P. i., Zhang, W., Dacks, J. B., Nighorn, A. J., & Evans, P. D. (2013). A Characterization of the Manduca sexta Serotonin Receptors in the Context of Olfactory Neuromodulation. PLoS ONE, 8(7).More infoPMID: 23922709;PMCID: PMC3726668;Abstract: Neuromodulation, the alteration of individual neuron response properties, has dramatic consequences for neural network function and is a phenomenon observed across all brain regions and taxa. However, the mechanisms underlying neuromodulation are made complex by the diversity of neuromodulatory receptors expressed within a neural network. In this study we begin to examine the receptor basis for serotonergic neuromodulation in the antennal lobe of Manduca sexta. To this end we cloned all four known insect serotonin receptor types from Manduca (the Ms5HTRs). We used phylogenetic analyses to classify the Ms5HTRs and to establish their relationships to other insect serotonin receptors, other insect amine receptors and the vertebrate serotonin receptors. Pharmacological assays demonstrated that each Ms5HTR was selective for serotonin over other endogenous amines and that serotonin had a similar potency at all four Ms5HTRs. The pharmacological assays also identified several agonists and antagonists of the different Ms5HTRs. Finally, we found that the Ms5HT1A receptor was expressed in a subpopulation of GABAergic local interneurons suggesting that the Ms5HTRs are likely expressed heterogeneously within the antennal lobe based on functional neuronal subtype. © 2013 Dacks et al.
- Gage, S. L., Daly, K. C., & Nighorn, A. (2013). Nitric oxide affects short-term olfactory memory in the antennal lobe of manduca sexta. Journal of Experimental Biology, 216(17), 3294-3300.More infoPMID: 23685973;PMCID: PMC3737371;Abstract: Nitric oxide (NO) is thought to play an important neuromodulatory role in olfaction. We are using the hawkmoth Manduca sexta to investigate the function of NO signaling in the antennal lobe (AL; the primary olfactory network in invertebrates). We have found previously that NO is present at baseline levels, dramatically increases in response to odor stimulation, and alters the electrophysiology of AL neurons. It is unclear, however, how these effects contribute to common features of olfactory systems such as olfactory learning and memory, odor detection and odor discrimination. In this study, we used chemical detection and a behavioral approach to further examine the function of NO in the AL. We found that basal levels of NO fluctuate with the daily light cycle, being higher during the nocturnal active period. NO also appears to be necessary for short-term olfactory memory. NO does not appear to affect odor detection, odor discrimination between dissimilar odorants, or learning acquisition. These findings suggest a modulatory role for NO in the timing of olfactory-guided behaviors. © 2013. Published by The Company of Biologists Ltd.
- Dacks, A. M., Riffell, J. A., Martin, J. P., Gage, S. L., & Nighorn, A. J. (2012). Olfactory modulation by dopamine in the context of aversive learning. Journal of Neurophysiology, 108(2), 539-550.More infoPMID: 22552185;PMCID: PMC3404788;Abstract: The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. © 2012 the American Physiological Society.
- Higgins, M., Miller, M., & Nighorn, A. (2012). Nitric oxide has differential effects on currents in different subsets of Manduca sexta Antennal lobe neurons. PLoS ONE, 7(8).More infoPMID: 22880032;PMCID: PMC3411793;Abstract: Nitric oxide has been shown to regulate many biological systems including olfaction. In the moth olfactory system nitric oxide is produced in the antennal lobe in response to odor stimulation and has complex effects on the activity of both projection neurons and local interneurons. To examine the cell autonomous effects of nitric oxide on these cells, we used patch-clamp recording in conjunction with pharmacological manipulation of nitric oxide to test the hypothesis that nitric oxide differentially regulates the channel properties of these different antennal lobe neuron subsets. We found that nitric oxide caused increasing inward currents in a subset of projection neurons while the effects on local neurons were variable but consistent within identifiable morphological subtypes. © 2012 Higgins et al.
- Oland, L., Mallory, H., Gibson, N., Hayashi, J., Nighorn, A., & Tolbert, L. (2012). Direct and glia-mediated effects of GABA on development of central olfactory neurons. Neuron Glia Biol, 7(2-4), 143-161.
- Dacks, A. M., & Nighorn, A. J. (2011). The organization of the antennal lobe correlates not only with phylogenetic relationship, but also life history: A basal hymenopteran as exemplar. Chemical Senses, 36(2), 209-220.More infoPMID: 21059697;PMCID: PMC3105589;Abstract: The structure of the brain is a consequence of selective pressures and the ancestral brain structures modified by those pressures. The Hymenoptera are one of the most behaviorally complex insect orders, and the olfactory system of honeybees (one of the most derived members) has been extensively studied. To understand the context in which the olfactory system of the Hymenoptera evolved, we performed a variety of immunocytochemical and anatomical labeling techniques on the antennal lobes (ALs) of one of its most primitive members, the sawflies, to provide a comparison between the honeybee and other insect model species. The olfactory receptor neurons project from the antennae to fill the entire glomerular volume but do not form distinct tracts as in the honeybee. Labeling of projection neurons revealed 5 output tracts similar to those in moths and immunolabeling for several transmitters revealed distinct populations of local interneurons and centrifugal neurons that were also similar to moths. There were, however, no histaminergic or dopaminergic AL neurons. The similarities between sawflies and moths suggest that along with the great radiation and increased complexity of behavioral repertoire of the Hymenoptera, there were extensive modifications of AL structure. © The Author 2010. Published by Oxford University Press. All rights reserved.
- Dacks, A. M., Reisenman, C. E., Paulk, A. C., & Nighorn, A. J. (2010). Histamine-immunoreactive local neurons in the antennal lobes of the hymenoptera. Journal of Comparative Neurology, 518(15), 2917-2933.More infoPMID: 20533353;PMCID: PMC2886666;Abstract: Neural networks receive input that is transformed before being sent as output to higher centers of processing. These transformations are often mediated by local interneurons (LNs) that influence output based on activity across the network. In primary olfactory centers, the LNs that mediate these lateral interactions are extremely diverse. For instance, the antennal lobes (ALs) of bumblebees possess both γ-aminobutyric acid (GABA)-and histamine-immunoreactive (HA-ir) LNs, and both are neurotransmitters associated with fast forms of inhibition. Although the GABAergic network of the AL has been extensively studied, we sought to examine the anatomical features of the HA-ir LNs in relation to the other cellular elements of the bumblebee AL. As a population, HA-ir LNs densely innervate the glomerular core and sparsely arborize in the outer glomerular rind, overlapping with the terminals of olfactory receptor neurons. Individual fills of HA-ir LNs revealed heavy arborization of the outer ring of a single "principal" glomerulus and sparse arborization in the core of other glomeruli. In contrast, projection neurons and GABA-immunoreactive LNs project throughout the glomerular volume. To provide insight into the selective pressures that resulted in the evolution of HA-ir LNs, we determined the phylogenetic distribution of HA-ir LNs in the AL. HA-ir LNs were present in all but the most basal hymenopteran examined, although there were significant morphological differences between major groups within the Hymenoptera. The ALs of other insect taxa examined lacked HA-ir LNs, suggesting that this population of LNs arose within the Hymenoptera and underwent extensive morphological modification. © 2010 Wiley-Liss, Inc.
- Dacks, A. M., Green, D. S., Root, C. M., Nighorn, A. J., & Wang, J. W. (2009). Serotonin modulates olfactory processing in the antennal lobe of drosophila. Journal of Neurogenetics, 23(4), 366-377.More infoPMID: 19863268;PMCID: PMC2850205;Abstract: Sensory systems must be able to extract features of environmental cues within the context of the different physiological states of the organism and often temper their activity in a state-dependent manner via the process of neuromodulation. We examined the effects of the neuromodulator serotonin on a well-characterized sensory circuit, the antennal lobe of Drosophila melanogaster, using two-photon microscopy and the genetically expressed calcium indicator, G-CaMP. Serotonin enhances sensitivity of the antennal lobe output projection neurons in an odor-specific manner. For odorants that sparsely activate the antennal lobe, serotonin enhances projection neuron responses and causes an offset of the projection neuron tuning curve, most likely by increasing projection neuron sensitivity. However, for an odorant that evokes a broad activation pattern, serotonin enhances projection neuron responses in some, but not all, glomeruli. Further, serotonin enhances the responses of inhibitory local interneurons, resulting in a reduction of neurotransmitter release from the olfactory sensory neurons via GABAB receptor-dependent presynaptic inhibition, which may be a mechanism underlying the odorant-specific modulation of projection neuron responses. Our data suggest that the complexity of serotonin modulation in the antennal lobe accommodates coding stability in a glomerular pattern and flexible projection neuron sensitivity under different physiological conditions. © 2009 Informa UK Ltd All rights reserved.
- Coate, T. M., Swanson, T. L., Proctor, T. M., Nighorn, A. J., & Copenhaver, P. F. (2007). Eph receptor expression defines midline boundaries for ephrin-positive migratory neurons in the enteric nervous system of Manduca sexta. Journal of Comparative Neurology, 502(2), 175-191.More infoPMID: 17348007;PMCID: PMC1828045;Abstract: Eph receptor tyrosine kinases and their ephrin ligands participate in the control of neuronal growth and migration in a variety of contexts, but the mechanisms by which they guide neuronal motility are still incompletely understood. By using the enteric nervous system (ENS) of the tobacco hornworm Manduca sexta as a model system, we have explored whether Manduca ephrin (MsEphrin; a GPI-linked ligand) and its Eph receptor (MsEph) might regulate the migration and outgrowth of enteric neurons. During formation of the Manduca ENS, an identified set of ∼300 neurons (EP cells) populates the enteric plexus of the midgut by migrating along a specific set of muscle bands forming on the gut, but the neurons strictly avoid adjacent interband regions. By determining the mRNA and protein expression patterns for MsEphrin and the MsEph receptor and by examining their endogenous binding patterns within the ENS, we have demonstrated that the ligand and its receptor are distributed in a complementary manner: MsEphrin is expressed exclusively by the migratory EP cells, whereas the MsEph receptor is expressed by midline interband cells that are normally inhibitory to migration. Notably, MsEphrin could be detected on the filopodial processes of the EP cells that extended up to but not across the midline cells expressing the MsEph receptor. These results suggest a model whereby MsEphrin-dependent signaling regulates the response of migrating neurons to a midline inhibitory boundary, defined by the expression of MsEph receptors in the developing ENS. © 2007 Wiley-Liss, Inc.
- Settembrini, B. P., Coronel, M. F., Nowicki, S., Nighorn, A. J., & Villar, M. J. (2007). Distribution and characterization of nitric oxide synthase in the nervous system of Triatoma infestans (Insecta: Heteroptera). Cell and Tissue Research, 328(2), 421-430.More infoPMID: 17235602;PMCID: PMC1868425;Abstract: The biochemical characterization of nitric oxide synthase (NOS) and its distribution in the central nervous system (CNS) were studied in the heteropteran bug Triatoma infestans. NOS-like immunoreactivity was found in the brain, subesophageal ganglion, and thoracic ganglia by using immunocytochemistry. In the protocerebrum, NOS-immunoreactive (IR) somata were detected in the anterior, lateral, and posterior soma rinds. In the optic lobe, numerous immunostained somata were observed at the level of the first optic chiasma, around the lobula, and in the proximal optic lobe. In the deutocerebrum, NOS-IR perikarya were mainly observed in the lateral soma rind, surrounding the sensory glomeruli, and a few cell bodies were seen in association with the antennal mechanosensory and motor neuropil. No immunostaining could be detected in the antennal nerve. The subesophageal and prothoracic ganglia contained scattered immunostained cell bodies. NOS-IR somata were present in all the neuromeres of the posterior ganglion. Western blotting showed that a universal NOS antiserum recognized a band at 134 kDa, in agreement with the expected molecular weight of the protein. Analysis of the kinetics of nitric oxide production revealed a fully active enzyme in tissue samples of the CNS of T. infestans. © 2007 Springer-Verlag.
- Vidovic, M., Nighorn, A., Koblar, S., & Maleszka, R. (2007). Eph receptor and ephrin signaling in developing and adult brain of the honeybee (Apis mellifera). Developmental Neurobiology, 67(2), 233-251.More infoPMID: 17443785;PMCID: PMC2084376;Abstract: Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain development are well established. Their involvement in the modulation of mammalian synaptic structure and physiology is also emerging. However, less is known of their effects on brain development and their function in adult invertebrate nervous systems. Here, we report on the characterization of Eph receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their role in learning and memory. In situ hybridization for mRNA expression showed a uniform distribution of expression of both genes across the developing pupal and adult brain. However, in situ labeling with Fc fusion proteins indicated that the AmEphR and Amephrin proteins were differentially localized to cell body regions in the mushroom bodies and the developing neuropiles of the antennal and optic lobes. In adults, AmEphR protein was localized to regions of synaptic contacts in optic lobes, in the glomeruli of antennal lobes, and in the medial lobe of the mushroom body. The latter two regions are involved in olfactory learning and memory in the honeybee. Injections of EphR-Fc and ephrin-Fc proteins into the brains of adult bees, 1 h before olfactory conditioning of the proboscis extension reflex, significantly reduced memory 24 h later. Experimental amnesia in the group injected with ephrin-Fc was apparent 1 h post-training. Experimental amnesia was also induced by post-training injections with ephrin-Fc suggesting a role in recall. This is the first demonstration that Eph molecules function to regulate the formation of memory in insects. © 2006 Wiley Periodicals, Inc.
- Wilson, C. H., Christensen, T. A., & Nighorn, A. J. (2007). Inhibition of nitric oxide and soluble guanylyl cyclase signaling affects olfactory neuron activity in the moth, Manduca sexta. Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology, 193(7), 715-728.More infoPMID: 17551736;PMCID: PMC2629079;Abstract: Nitric oxide is emerging as an important modulator of many physiological processes including olfaction, yet the function of this gas in the processing of olfactory information remains poorly understood. In the antennal lobe of the moth, Manduca sexta, nitric oxide is produced in response to odor stimulation, and many interneurons express soluble guanylyl cyclase, a well-characterized nitric oxide target. We used intracellular recording and staining coupled with pharmacological manipulation of nitric oxide and soluble guanylyl cyclase to test the hypothesis that nitric oxide modulates odor responsiveness in olfactory interneurons through soluble guanylyl cyclase-dependent pathways. Nitric oxide synthase inhibition resulted in pronounced effects on the resting level of firing and the responses to odor stimulation in most interneurons. Effects ranged from bursting to strong attenuation of activity and were often accompanied by membrane depolarization coupled with a change in input resistance. Blocking nitric oxide activation of soluble guanylyl cyclase signaling mimicked the effects of nitric oxide synthase inhibitors in a subset of olfactory neurons, while other cells were differentially affected by this treatment. Together, these results suggest that nitric oxide is required for proper olfactory function, and likely acts through soluble guanylyl cyclase-dependent and -independent mechanisms in different subsets of neurons. © 2007 Springer-Verlag.
- Boyle, M., Nighorn, A., & Thomas, J. B. (2006). Drosophila Eph receptor guides specific axon branches of mushroom body neurons. Development, 133(9), 1845-1854.More infoPMID: 16613832;PMCID: PMC1794001;Abstract: The conserved Eph receptors and their Ephrin ligands regulate a number of developmental processes, including axon guidance. In contrast to the large vertebrate Eph/Ephrin family, Drosophila has a single Eph receptor and a single Ephrin ligand, both of which are expressed within the developing nervous system. Here, we show that Eph and Ephrin can act as a functional receptor-ligand pair in vivo. Surprisingly, and in contrast to previous results using RNA-interference techniques, embryos completely lacking Eph function show no obvious axon guidance defects. However, Eph/Ephrin signaling is required for proper development of the mushroom body. In wild type, mushroom body neurons bifurcate and extend distinct branches to different target areas. In Eph mutants, these neurons bifurcate normally, but in many cases the dorsal branch fails to project to its appropriate target area. Thus, Eph/Ephrin signaling acts to guide a subset of mushroom body branches to their correct synaptic targets.
- Dacks, A. M., Dacks, J. B., Christensen, T. A., & Nighorn, A. J. (2006). The cloning of one putative octopamine receptor and two putative serotonin receptors from the tobacco hawkmoth, Manduca sexta. Insect Biochemistry and Molecular Biology, 36(9), 741-747.More infoPMID: 16935223;PMCID: PMC1794002;Abstract: Serotonin and octopamine (OA) are biogenic amines that are active throughout the nervous systems of insects, affecting sensory processing, information coding and behavior. As an initial step towards understanding the modulatory roles of these amines in olfactory processing we cloned two putative serotonin receptors (Ms5HT1A and Ms5HT1B) and one putative OA (MsOAR) receptor from the moth Manduca sexta. Ms5HT1A and Ms5HT1B were both similar to 5HT1-type receptors but differed from each other in their N-terminus and 3rd cytoplasmic loop. Ms5HT1A was nearly identical to a serotonin receptor from Heliothis virescens and Ms5HT1B was almost identical to a serotonin receptor from Bombyx mori. The sequences for homologs of Ms5HT1A from B. mori and Ms5HT1B from H. virescens were also obtained, suggesting that the Lepidoptera likely have at least two serotonin receptors. The MsOAR shares significant sequence homology with pharmacologically characterized OA receptors, but less similarity to putative OA/tyramine receptors from the moths B. mori and H. virescens. Using the MsOAR sequence, fragments encoding putative OA receptors were obtained from B. mori and H. virescens, suggesting that MsOAR is the first OA receptor cloned from a lepidopteran. © 2006 Elsevier Ltd. All rights reserved.
- Mammen, A., Simpson, P. J., Nighorn, A., Imanishi, Y., Palczewski, K., Ronnett, G. V., & Moon, C. (2005). Erratum: Hippocalcin in the olfactory epithelium: A mediator of second messenger signaling (Biochemical Biophysical Research Communications (2004) 322 (1131-1139) DOI: 10.1016/j.bbrc.2004.07.123). Biochemical and Biophysical Research Communications, 326(3), 695-.
- Collmann, C., Carlsson, M. A., Hansson, B. S., & Nighorn, A. (2004). Odorant-evoked nitric oxide signals in the antennal lobe of Manduca sexta. Journal of Neuroscience, 24(27), 6070-6077.More infoPMID: 15240798;PMCID: PMC1794326;Abstract: The gaseous signaling molecule nitric oxide (NO) can affect the activities of neurons and neural networks in many different systems. The strong expression of NO synthase (NOS) in the primary synaptic neuropil (the antennal lobe in insects and the olfactory bulb in vertebrates) of the olfactory system of most organisms, and the unique spheroidal geometry of olfactory glomeruli in those neuropils, have led to suggestions that NO signaling is important for processing olfactory information. No direct evidence exists, however, that NO signals are produced in olfactory glomeruli. We investigated the production of NO in the antennal lobe of the moth, Manduca sexta, by using immunocytochemistry and real-time optical imaging with a NO-sensitive fluorescent marker, diaminofluorescein diacetate. We confirmed that NOS was expressed in the axons of olfactory receptor neurons projecting to all glomeruli. Soluble guanylyl cyclase, the best characterized target of NO, was found in a subset of postsynaptic antennal lobe neurons that included projection neurons, a small number of GABA-immunoreactive neurons, and a serotonin-immunoreactive neuron. We found that odorant stimulation evoked NO signals that were reproducible and spatially focused. Different odorants evoked spatially distinct patterns of NO production. Increased concentrations of pheromone and plant odorants caused increases in peak signal intensity. Increased concentrations of plant odorants also evoked a dramatic increase in signal area. The results of these experiments show clearly that odorant stimulation can evoke NO production in the olfactory system. The NO signals produced are likely to play an important role in processing olfactory information.
- Mamman, A., Simpson, J. P., Nighorn, A., Imanishi, Y., Palczewski, K., Ronnett, G. V., & Moon, C. (2004). Hippocalcin in the olfactory epithelium: A mediator of second messenger signaling. Biochemical and Biophysical Research Communications, 322(4), 1131-1139.More infoPMID: 15336960;Abstract: Intracellular Ca 2+ plays an important role in a variety of second messenger cascades. The function of Ca 2+ is mediated, in part, by Ca 2+-binding proteins such as calmodulin, calretinin, calbindin, neurocalcin, recoverin, and visinin-like proteins (VILIPs). These proteins are highly expressed in rat olfactory receptor neurons (ORNs) and are localized to distinct intracellular regions. In the present study, we have identified another Ca 2+-binding protein, hippocalcin, in the rat olfactory epithelium (OE). Olfactory/brain hippocalcin shows high sequence homology with hippocalcins expressed in mice and humans. Hippocalcin was predominantly localized to the olfactory cilia, the site of the initial events of olfactory signal transduction, and was found to regulate the activity of ciliary adenylate cyclases (ACs) and particulate guanylyl cyclases (GCs) in a Ca 2+-dependent manner. These data indicate that hippocalcin is expressed in rat ORNs, and is likely to regulate second messenger cascades in a Ca 2+-dependent manner. © 2004 Elsevier Inc. All rights reserved.
- Schachtner, J., Huetteroth, W., Nighorn, A., & Honegger, H. (2004). Copper/Zinc Superoxide Dismutase-Like Immunoreactivity in the Metamorphosing Brain of the Sphinx Moth Manduca sexta. Journal of Comparative Neurology, 469(1), 141-152.More infoPMID: 14689479;Abstract: Cu/Zn superoxide dismutase (SOD) is part of the defense mechanism that protects cells from being damaged by reactive oxygen species. During metamorphosis of the nervous system, neurons undergo various fates, which are all coupled to high metabolic activities, such as proliferation, differentiation, pathfinding, and synaptogenesis. We describe the pattern of SOD immunoreactivity of identified neurons and neuron groups in the brain of Manduca sexta from the late larva through metamorphosis into adult. We focused on neurons of the developing antennal lobes, the optic lobes, and the central brain. Our results indicate the transient expression of SOD during phases in which the neurons develop their final adult identities. Our data also suggest that the SOD immunoreactivity may be used as an indicator for the period in which developing neurons form their synapses. We also observed SOD immunoreactivity within nitric oxide-sensitive cells as characterized by immunolabeling against 3′5′-cyclic guanosine monophosphate and soluble guanylyl cyclase, a novel finding in insects. © 2003 Wiley-Liss, Inc.
- Kaneko, M., & Nighorn, A. (2003). Interaxonal Eph-Ephrin Signaling May Mediate Sorting of Olfactory Sensory Axons in Manduca sexta. Journal of Neuroscience, 23(37), 11523-11538.More infoPMID: 14684856;Abstract: We have investigated possible roles of the Eph family receptor tyrosine kinases and their ligand ephrins in the developing primary olfactory nerve pathway in the moth Manduca sexta. The Manduca homologs of the Eph receptor (MsEph) and ephrin ligand (MsEphrin) are most closely related to Drosophila Eph and ephrin, respectively. In situ labeling with Fc-fusion probes, in which IgG Fc was linked to the extracellular domain of MsEph (Eph-Fc) or MsEphrin (ephrin-Fc), reveals that both Eph receptors and ephrins are expressed on axons of olfactory receptor cells (ORCs) during their ingrowth to the primary center, the antennal lobe (AL). Interestingly, Eph receptors and ephrins are differentially distributed among identifiable glomeruli such that glomeruliwith high receptor staining show little or no ligand staining, and vice versa, suggesting a complementary Eph-ephrin expression by subsets of ORC axons innervating a particular set of glomeruli. In contrast, neither Eph receptors nor ephrins are detectable in intrinsic components of the AL. In vitro, ephrin-Fc and Eph-Fc, when present homogeneously in the substratum, inhibit neurite outgrowth from olfactory epithelial explants. Moreover, in patterned substratum, neurites growing on the standard substratum turn or stop after encountering the test substratum containing ephrin-Fc. These in vitro observations indicate that MsEphrin can act as an inhibitor/repulsive cue for ORC axons. Based on results from in situ and in vitro experiments, we hypothesize that Eph receptors and ephrins mediate axon sorting and fasciculation through repulsive axon-axon interactions.
- Morton, D. B., & Nighorn, A. (2003). MsGC-II, a receptor guanylyl cyclase isolated from the CNS of Manduca sexta that is inhibited by calcium. Journal of Neurochemistry, 84(2), 363-372.More infoPMID: 12558998;Abstract: We describe the cloning of a receptor guanylyl cyclase, MsGC-II, from the CNS of the insect Manduca sexta. Sequence comparisons with other receptor guanylyl cyclases show that MsGC-II is most similar to a predicted guanylyl cyclase in the Drosophila genome and to vertebrate retinal guanylyl cyclases. When expressed in COS-7 cells, MsGC-II exhibited a low level of basal activity that was nearly abolished in the presence of 10 μM calcium. Incubation with either a mammalian guanylyl cyclase-activating protein or Drosophila frequenin resulted in only mild stimulation of activity, whereas incubation of COS-7 cells expressing MsGC-II with a variety of Manduca tissue extracts failed to stimulate enzyme activity above basal levels. Analysis of the tissue distribution of MsGC-II revealed that it is nervous system specific. In the adult, MsGC-II is present in neurons in the optic lobes, antennal lobes and cellular cortex, but it is most highly expressed in subsets of intrinsic mushroom body neurons. Thus, MsGC-II appears to be a neural-specific receptor guanylyl cyclase whose activity may be regulated either directly or indirectly by calcium.
- Kumar, D. V., Nighorn, A., & A., P. (2002). Role of Nova-1 in regulating α2N, a novel glycine receptor splice variant, in developing spinal cord neurons. Journal of Neurobiology, 52(2), 156-165.More infoPMID: 12124753;Abstract: Inhibitory glycine receptor (GlyR) subunits undergo developmental regulation, but the molecular mechanisms of GlyR regulation in developing neurons are little understood. Using RT-PCR, we investigated the regulation of GlyR α-subunit splice forms during the development of the spinal cord of the rat. Experiments to compare the amounts of mRNA for two known splice variants of the GlyR α2 subunit, α2A and α2B, in the developing rat spinal cord revealed the presence of an additional, novel variant that lacked any exon 3, herein named "α2N." Examination of the RNA from spinal cords of different-aged rats showed a dramatic down-regulation of α2N during prenatal development: α2N mRNA formed a significant portion of the α2 subunit pool at E14, but its relative level was reduced by 85% by birth and was undetectable in adults. Two proteins previously implicated in regulating the splicing of GlyR α2 pre-mRNA, the neurooncological ventral antigen-1 (Nova-1) and the brain isoform of the polypyrimidine tract binding protein (brPTB), underwent small changes over the same period that did not correlate directly with the changes in the level of α2N, calling into question their involvement in the developmental regulation of α2N. However, treatment of spinal cord neurons in culture with antisense oligonucleotides designed selectively to knock down one of three Nova-1 variants significantly altered the relative level of GlyR α2N, showing that Nova-1 isoforms can regulate GlyR α2 pre-mRNA splicing in developing neurons. These results provide evidence for a novel splice variant of the GlyR α2 subunit that undergoes dramatic developmental regulation, reveal the expression profiles of Nova-1 and brPTB in the developing spinal cord, and suggest that Nova-1 plays a role in regulating GlyR α2N in developing neurons. © 2002 Wiley Periodicals, Inc.
- Gibson, N. J., Roessler, W. R., Nighorn, A. J., Oland, L. A., Hildebrand, J. G., & Tolbert, L. P. (2001). Neuron-glia communication via nitric oxide is essential in establishing antennal-lobe structure in Manduca sexta. Developmental Biology, 240, 326-39.
- Nighorn, A., Simpson, P. J., & Morton, D. B. (2001). The novel guanylyl cyclase MsGC-I is strongly expressed in higher-order neuropils in the brain of Manduca sexta. Journal of Experimental Biology, 204(2), 305-314.More infoPMID: 11136616;Abstract: Guanylyl cyclases are usually characterized as being either soluble (sGCs) or receptor (rGCs). We have recently cloned a novel guanylyl cyclase, MsGC-I, from the developing nervous system of the hawkmoth Manduca sexta that cannot be classified as either an sGC or an rGC. MsGC-I shows highest sequence identity with receptor guanylyl cyclases throughout its catalytic and dimerization domains, but does not contain the ligand-binding, transmembrane or kinase-like domains characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C-terminal extension of 149 amino acid residues. In this paper, we report the expression of MsGC-I in the adult. Northern blots show that it is expressed preferentially in the nervous system, with high levels in the pharate adult brain and antennae. In the antennae, immunohistochemical analyses show that it is expressed in the cell bodies and dendrites, but not axons, of olfactory receptor neurons. In the brain, it is expressed in a variety of sensory neuropils including the antennal and optic lobes. It is also expressed in structures involved in higher-order processing including the mushroom bodies and central complex. This complicated expression pattern suggests that this novel guanylyl cyclase plays an important role in mediating cyclic GMP levels in the nervous system of Manduca sexta.
- Stengl, M., Zintl, R., Vente, J. D., & Nighorn, A. (2001). Localization of cGMP immunoreactivity and of soluble guanylyl cyclase in antennal sensilla of the hawkmoth Manduca sexta. Cell and Tissue Research, 304(3), 409-421.More infoPMID: 11456418;Abstract: The intracellular messenger cGMP (cyclic guanosine monophosphate) has been suggested to play a role in olfactory transduction in both invertebrates and vertebrates, but its cellular location within the olfactory system has remained elusive. We used cGMP immunocytochemistry to determine which antennal cells of the hawkmoth Manduca sexta are cGMP immunoreactive in the absence of pheromone. We then tested which antennal cells increase cGMP levels in response to nitric oxide (NO) and to long pheromonal stimuli, which the male encounters close to a calling female moth. In addition, we used in situ hybridization to determine which antennal cells express NO-sensitive soluble guanylyl cyclase. In response to long pheromonal stimuli with NO donors present, cGMP concentrations change in at least a subpopulation of pheromone-sensitive olfactory receptor neurons. These changes in cGMP concentrations in pheromone-dependent olfactory receptor neurons cannot be mimicked by the addition of NO donors in the absence of pheromone. NO stimulates sensilla chaetica type I and II, but not pheromone-sensitive trichoid sensilla, to high levels of cGMP accumulation as detected by immunocytochemistry. In situ hybridizations show that sensilla chaetica, but not sensilla trichodea, express detectable levels of mRNA coding for soluble guanylyl cyclase. These results suggest that intracellular rises in cGMP concentrations play a role in information processing in a subpopulation of pheromone-sensitive sensilla in Manduca sexta antennae, mediated by an NO-sensitive mechanism, but not an NO-dependent soluble guanylyl cyclase.
- Gibson, N. J., & Nighorn, A. (2000). Expression of nitric oxide synthase and soluble guanylyl cyclase in the developing olfactory system of Manduca sexta. Journal of Comparative Neurology, 422(2), 191-205.More infoPMID: 10842227;Abstract: The gaseous messenger nitric oxide (NO), with its ability to mediate both intercellular and intracellular communication, can play important roles in mediating cellular communication in both the development and the function of the nervous system. The authors investigated the possible role of NO signaling in the developing olfactory system (antennal lobe) of the moth Manduca sexta. NO synthase (NOS), the enzyme that generates NO, was localized by using immunocytochemistry, in situ hybridization, and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Although NADPH-d staining appears to be a poor indicator of the presence of NOS in this system, immunocytochemistry and in situ hybridization reveal that NOS is expressed in the axons of olfactory receptor neurons throughout development and in the perineurial sheath that covers the brain early in development. NOS is present in axon terminals as they form protoglomeruli, raising the possibility that NO mediates cell-cell interactions during antennal lobe development. NO-sensitive soluble guanylyl cyclase (sGC), one of the best characterized targets of NO, was localized in the developing olfactory system by using in situ hybridization and immunocytochemistry for the Manduca sexta sGCα1 subunit. The ability of the developing olfactory system to respond to exogenous NO also was examined by using cyclic guanosine monophosphate immunocytochemistry. sGC is expressed in mechanosensory neurons in the developing antenna and in many antennal lobe neurons in both the medial and lateral cell body clusters. Thus, NOS and sGC are expressed in a pattern that suggests that this signaling pathway may mediate intercellular communication during development of the olfactory system in Manduca sexta. (C) 2000 Wiley- Liss, Inc.
- Nighorn, A., Byrnes, K. A., & Morton, D. B. (1999). Identification and characterization of a novel β subunit of soluble guanylyl cyclase that is active in the absence of a second subunit and is relatively insensitive to nitric oxide. Journal of Biological Chemistry, 274(4), 2525-2531.More infoPMID: 9891024;Abstract: Previously characterized soluble guanylyl cyclases form α-β heterodimers that can be activated by the gaseous messenger, nitric oxide. In mammals, four subunits have been cloned, named α1, α2, β1, and β2. We have identified a novel soluble guanylyl cyclase isoform from the nervous system of the insect Manduca sexta that we have named M. sexta guanylyl cyclase β3 (MsGC-β3). It is most closely related to the mammalian β subunits but has several features that distinguish it from previously identified soluble cyclases. Most importantly, MsGC-β3 does not need to form heterodimers to form an active enzyme because guanylyl cyclase activity can be measured when it is expressed alone in COS-7 cells. Moreover, this activity is only weakly enhanced in the presence of the nitric oxide donor, sodium nitroprusside. Several of the amino acids in rat β1 subunits, previously identified as being important in heme binding or necessary for nitric oxide activation, are substituted with nonsimilar amino acids in MsGC- β3. There are also an additional 315 amino acids C-terminal to the catalytic domain of MsGC-β3 that have no sequence similarity to any known protein. Northern blot analysis shows that MsGC-β3 is primarily expressed in the nervous system of Manduca.
- Simpson, P. J., Nighorn, A., & Morton, D. B. (1999). Identification of a novel guanylyl cyclase that is related to receptor guanylyl cyclases, but lacks extracellular and transmembrane domains. Journal of Biological Chemistry, 274(7), 4440-4446.More infoPMID: 9933648;Abstract: We have identified a novel guanylyl cyclase, named MsGC-I, that is expressed in the nervous system of Manduca sexta. MsGC-I shows highest sequence identity with receptor guanylyl cyclases throughout its catalytic and dimerization domains but does not contain the ligand-binding, transmembrane, or kinase-like domains characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C-terminal extension of 149 amino acids that is not present in other receptor guanylyl cyclases. The sequence of MsGC-I contains no regions that show similarity to the regulatory domain of soluble guanylyl cyclases. Thus, MsGC-I appears to represent a member of a new class of guanylyl cyclases. We show that both a transcript and a protein of the sizes predicted from the MsGC-I cDNA are present in the nervous system of Manduca and that MsGC-I is expressed in a small population of neurons within the abdominal ganglia. When expressed in COS-7 cells, MsGC-I appears to exist as a soluble homodimer with high levels of basal guanylyl cyclase activity that is insensitive to stimulation by nitric oxide. Western blot analysis, however, shows that MsGC-I is localized to the particulate fraction of nervous system homogenates, suggesting that it may be membrane-associated in vivo.
- Nighorn, A., Qiu, Y., & Davis, R. L. (1994). Progress in understanding the Drosophila dnc locus. Comparative Biochemistry and Physiology -- Part B: Biochemistry and, 108(1), 1-9.More infoPMID: 8205385;Abstract: The genetic dissection of learning and memory in Drosophila is two decades old. Recently, a great deal of progress has been made towards isolating new mutants as well as towards a better understanding of the originally isolated ones. This paper reviews the recent developments in the understanding of the structure and function of the gene identified by the first and best-characterized of these mutants, the Drosophila dunce mutant. © 1994.
- Nighorn, A., Healy, M. J., & Davis, R. L. (1991). The cyclic AMP phosphodiesterase encoded by the Drosophila dunce gene is concentrated in the mushroom body neuropil. Neuron, 6(3), 455-467.More infoPMID: 1848082;Abstract: Drosophila dunce (dnc) flies are defective in learning and memory as a result of lesions in the gene that codes for a cAMP-specific phosphodiesterase (PDE). Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil - areas previously implicated in learning and memory. In situ hybridization demonstrated that dnc RNA was enriched in the mushroom body perikarya. The mushroom bodies of third instar larval brains were also stained intensely by the antibody, suggesting that the dnc PDE plays an important role in these neurons throughout their development. The role of the dnc PDE in mushroom body physiology is discussed, and a circuit model describing a possible role of the mushroom bodies in mediating olfactory learning and memory is presented.
- Nighorn, A. J. (2015, April). Circadian effects on olfactory learning. April Datablitz.
- Gage, S., & Nighorn, A. (2013, Fall). The Role of Nitric Oxide in Memory is Modulated by Circadian Time. Society for Neuroscience. San Diego, CA.
- Gage, S., & Nighorn, A. (2012, October). Nitric oxide affects short-term olfactory memory in the antennal lobe of Manduca sexta. Society for Neuroscience. New Orleans, LA.