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Chemical signalling in the Drosophila brain: GABA, short neuropeptide F and their receptors
Stockholm University, Faculty of Science, Department of Zoology.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gamma-aminobutyric acid (GABA) and short neuropeptide F (sNPF) are widespread signalling molecules in the brain of insects. In order to understand more about the signalling and to some extent start to unravel the functional roles of these two substances, this study has examined the locations of the transmitters and their receptors in the brain of the fruit fly Drosophila melanogaster using immunocytochemistry in combination with Gal4/UAS technique. The main focus is GABA and sNPF in feeding circuits and in the olfactory system. We found both GABA receptor types in neurons in many important areas of the Drosophila brain including the antennal lobe, mushroom body and the central body complex. The metabotropic GABAB receptor (GABABR) is expressed in a pattern similar to the ionotropic GABAAR, but some distribution differences can be distinguished (paper I). The insulin producing cells contain only GABABR, whereas the GABAAR is localized on neighbouring neurons. We found that GABA regulates the production and release of insulin-like peptides via GABABRs (paper II). The roles of sNPFs in feeding and growth have previously been established, but the mechanisms behind this are unclear. We mapped the distribution of sNPF with antisera to the sNPF precursor and found the peptide in a large variety of interneurons, including the Kenyon cells of the mushroom bodies, as well as in olfactory sensory neurons that send axons to the antennal lobe (paper III). We also mapped the distribution of the sNPF receptor in larval tissues and found localization in six median neurosecretory cells that are not insulin-producing cells, in neuronal branches in the larval antennal lobe and in processes innervating the mushroom bodies (paper IV).

In summary, we have studied two different signal substances in the Drosophila brain (GABA and sNPF) in some detail. We found that these substances and their receptors are widespread, that both sNPF and GABA act in very diverse systems and that they presumably play roles in feeding, metabolism and olfaction.

Place, publisher, year, edition, pages
Stockholm: Department of Zoology, Stockholm University , 2011. , 40 p.
Keyword [en]
Insect nervous system, Drosophila, GABA, sNPF, GPCR, ion channel receptor, feeding, metabolic stress, olfaction, antennal, lobe, mushroom body
National Category
Zoology
Research subject
Functional Zoomorphology
Identifiers
URN: urn:nbn:se:su:diva-56476ISBN: 978-91-7447-291-2OAI: oai:DiVA.org:su-56476DiVA: diva2:411541
Public defence
2011-05-27, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.Available from: 2011-05-05 Created: 2011-04-18 Last updated: 2014-10-28Bibliographically approved
List of papers
1. gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter.
Open this publication in new window or tab >>gamma-Aminobutyric acid (GABA) signaling components in Drosophila: immunocytochemical localization of GABA(B) receptors in relation to the GABA(A) receptor subunit RDL and a vesicular GABA transporter.
2007 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 505, no 1, 18-31 p.Article in journal (Refereed) Published
Abstract [en]

γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in insects and is widely distributed in the central nervous system (CNS). GABA acts on ion channel receptors (GABAAR) for fast inhibitory transmission and on G-protein-coupled ones (GABABR) for slow and modulatory action. We used immunocytochemistry to map GABABR sites in the Drosophila CNS and compared the distribution with that of the GABAAR subunit RDL. To identify GABAergic synapses, we raised an antiserum to the vesicular GABA transporter (vGAT). For general GABA distribution, we utilized an antiserum to glutamic acid decarboxylase (GAD1) and a gad1-GAL4 to drive green fluorescent protein. GABABR-immunoreactive (IR) punctates were seen in specific patterns in all major neuropils of the brain. Most abundant labeling was seen in the mushroom body calyces, ellipsoid body, optic lobe neuropils, and antennal lobes. The RDL distribution is very similar to that of GABABR-IR punctates. However, the mushroom body lobes displayed RDL-IR but not GABABR-IR material, and there were subtle differences in other areas. The vGAT antiserum labeled punctates in the same areas as the GABABR and appeared to display presynaptic sites of GABAergic neurons. Various GAL4 drivers were used to analyze the relation between GABABR distribution and identified neurons in adults and larvae. Our findings suggest that slow GABA transmission is very widespread in the Drosophila CNS and that fast RDL-mediated transmission generally occurs at the same sites. J. Comp. Neurol. 505:18–31, 2007.

Keyword
insect central nervous system;inhibition;G-protein-coupled receptor;ion channel receptor;glutamic acid decarboxylase
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-19459 (URN)10.1002/cne.21472 (DOI)000250117800002 ()17729251 (PubMedID)
Available from: 2007-11-12 Created: 2007-11-12 Last updated: 2014-10-28Bibliographically approved
2. Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila
Open this publication in new window or tab >>Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila
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2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 12, e15780- p.Article in journal (Refereed) Published
Abstract [en]

Insulin-like peptides (ILPs) regulate growth, reproduction, metabolic homeostasis, life span and stress resistance in worms, flies and mammals. A set of insulin producing cells (IPCs) in the Drosophila brain that express three ILPs (DILP2, 3 and 5) have been the main focus of interest in hormonal DILP signaling. Little is, however, known about factors that regulate DILP production and release by these IPCs. Here we show that the IPCs express the metabotropic GABA(B) receptor (GBR), but not the ionotropic GABA(A) receptor subunit RDL. Diminishing the GBR expression on these cells by targeted RNA interference abbreviates life span, decreases metabolic stress resistance and alters carbohydrate and lipid metabolism at stress, but not growth in Drosophila. A direct effect of diminishing GBR on IPCs is an increase in DILP immunofluorescence in these cells, an effect that is accentuated at starvation. Knockdown of irk3, possibly part of a G protein-activated inwardly rectifying K(+) channel that may link to GBRs, phenocopies GBR knockdown in starvation experiments. Our experiments suggest that the GBR is involved in inhibitory control of DILP production and release in adult flies at metabolic stress and that this receptor mediates a GABA signal from brain interneurons that may convey nutritional signals. This is the first demonstration of a neurotransmitter that inhibits insulin signaling in its regulation of metabolism, stress and life span in an invertebrate brain.

National Category
Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-53298 (URN)10.1371/journal.pone.0015780 (DOI)000285793600039 ()21209905 (PubMedID)
Available from: 2011-01-21 Created: 2011-01-21 Last updated: 2014-10-28Bibliographically approved
3. A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions
Open this publication in new window or tab >>A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions
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2008 (English)In: BMC neuroscience (Online), ISSN 1471-2202, Vol. 9, no 1, 90-125 p.Article in journal (Refereed) Published
Abstract [en]

Background

Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS) of Drosophila in relation to other neuronal markers.

Results

There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7).

Conclusion

It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator/co-transmitter in various CNS circuits, including olfactory circuits both at the level of the first synapse and at the mushroom body output level. Some of the sNPF immunoreactive axons terminate in close proximity to neurosecretory cells producing ILPs and adipokinetic hormone, indicating that sNPF also might regulate hormone production or release.

Place, publisher, year, edition, pages
Biomed Central, 2008
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-14620 (URN)10.1186/1471-2202-9-90 (DOI)000260256900001 ()18803813 (PubMedID)
Available from: 2008-10-15 Created: 2008-10-15 Last updated: 2014-10-28Bibliographically approved
4. Distribution of short neuropeptide F and its receptorin the chemosensory and neuroendocrine systemsof larval Drosophila
Open this publication in new window or tab >>Distribution of short neuropeptide F and its receptorin the chemosensory and neuroendocrine systemsof larval Drosophila
(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-56372 (URN)
Available from: 2011-04-15 Created: 2011-04-14 Last updated: 2014-10-13

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Enell, Lina E.
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