Abstract
GABAergic neurotransmitter systems are important for many cognitive processes, including learning and memory. We identified a single neuron in each hemisphere of the Drosophila brain, the anterior paired lateral (APL) neuron, as a GABAergic neuron that broadly innervated the mushroom bodies. Reducing GABA synthesis in the APL neuron enhanced olfactory learning, suggesting that the APL neuron suppressed learning by releasing the inhibitory neurotransmitter GABA. Functional optical-imaging experiments revealed that the APL neuron responded to both odor and electric-shock stimuli that was presented to the fly with increases of intracellular calcium and released neurotransmitter. Notably, a memory trace formed in the APL neuron by pairing odor with electric shock. This trace was detected as a reduced calcium response in the APL neuron after conditioning specifically to the trained odor. These results demonstrate a mutual suppression between the GABAergic APL neuron and olfactory learning, and emphasize the functional neuroplasticity of the GABAergic system as a result of learning.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Freund, T.F. & Buzsaki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996).
Collinson, N. et al. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the α5 subunit of the GABAA receptor. J. Neurosci. 22, 5572–5580 (2002).
Harrison, J.B. et al. Immunocytochemical mapping of a C-terminus anti-peptide antibody to the GABA receptor subunit RDL in the nervous system in Drosophila melanogaster. Cell Tissue Res. 284, 269–278 (1996).
Liu, X., Krause, W.C. & Davis, R.L. GABAA receptor RDL inhibits Drosophila olfactory associative learning. Neuron 56, 1090–1102 (2007).
Yasuyama, K., Meinertzhagen, I.A. & Schürmann, F.W. Synaptic organization of the mushroom body calyx in Drosophila melanogaster. J. Comp. Neurol. 445, 211–226 (2002).
Schwaerzel, M., Heisenberg, M. & Zars, T. Extinction antagonizes olfactory memory at the subcellular level. Neuron 35, 951–960 (2002).
Jefferis, G.S. et al. Comprehensive maps of Drosophila higher olfactory centers: spatially segregated fruit and pheromone representation. Cell 128, 1187–1203 (2007).
Wong, A.M., Wang, J.W. & Axel, R. Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell 109, 229–241 (2002).
Stocker, R.F., Heimbeck, G., Gendre, N. & de Belle, J.S. Neuroblast ablation in Drosophila P[GAL4] lines reveals origins of olfactory interneurons. J. Neurobiol. 32, 443–456 (1997).
Tanaka, N.K., Tanimoto, H. & Ito, K. Neuronal assemblies of the Drosophila mushroom body. J. Comp. Neurol. 508, 711–755 (2008).
Yasuyama, K., Meinertzhagen, I.A. & Schürmann, F.W. Synaptic connections of cholinergic antennal lobe relay neurons innervating the lateral horn neuropile in the brain of Drosophila melanogaster. J. Comp. Neurol. 466, 299–315 (2003).
McGuire, S.E., Le, P.T. & Davis, R.L. The role of Drosophila mushroom body signaling in olfactory memory. Science 293, 1330–1333 (2001).
Kitamoto, T. Conditional disruption of synaptic transmission induces male-male courtship behavior in Drosophila. Proc. Natl. Acad. Sci. USA 99, 13232–13237 (2002).
Küppers, B., Sánchez-Soriano, N., Letzkus, J., Technau, G.M. & Prokop, A. In developing Drosophila neurones the production of gamma-amino butyric acid is tightly regulated downstream of glutamate decarboxylase translation and can be influenced by calcium. J. Neurochem. 84, 939–951 (2003).
Dietzl, G. et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448, 151–156 (2007).
Hanesch, U., Fischbach, K.-F. & Heisenberg, M. Neuronal architecture of the central complex in Drosophila melanogaster. Cell Tissue Res. 257, 343–366 (1989).
Acebes, A., Grosjean, Y., Everaerts, C. & Ferveur, J.F. Cholinergic control of synchronized seminal emissions in Drosophila. Curr. Biol. 14, 704–710 (2004).
Keene, A.C. et al. Diverse odor-conditioned memories require uniquely timed dorsal paired medial neuron output. Neuron 44, 521–533 (2004).
Reiff, D.F. et al. In vivo performance of genetically encoded indicators of neural activity in flies. J. Neurosci. 25, 4766–4778 (2005).
Miesenböck, G., De Angelis, D.A. & Rothman, J.E. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394, 192–195 (1998).
Yu, D., Ponomarev, A. & Davis, R.L. Altered representation of the spatial code for odors after olfactory classical conditioning; memory trace formation by synaptic recruitment. Neuron 42, 437–449 (2004).
Grünewald, B. Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera. J. Comp. Neurol. 404, 114–126 (1999).
Grünewald, B. Physiological properties and response modulations of mushroom body feedback neurons during olfactory learning in the honeybee, Apis mellifera. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 185, 565–576 (1999).
Liu, X. & Davis, R.L. Insect olfactory memory in time and space. Curr. Opin. Neurobiol. 16, 679–685 (2006).
Wang, Y., Mamiya, A., Chiang, A.S. & Zhong, Y. Imaging of an early memory trace in the Drosophila mushroom body. J. Neurosci. 28, 4368–4376 (2008).
Berry, J., Krause, W.C. & Davis, R.L. Olfactory memory traces in Drosophila. Prog. Brain Res. 169, 293–304 (2008).
Riemensperger, T., Voller, T., Stock, P., Buchner, E. & Fiala, A. Punishment prediction by dopaminergic neurons in Drosophila. Curr. Biol. 15, 1953–1960 (2005).
Yu, D., Keene, A.C., Srivatsan, A., Waddell, S. & Davis, R.L. Drosophila DPM neurons form a delayed and branch-specific memory trace after olfactory classical conditioning. Cell 123, 945–957 (2005).
Yu, D., Akalal, D.B. & Davis, R.L. Drosophila α/β mushroom body neurons form a branch-specific, long-term cellular memory trace after spaced olfactory conditioning. Neuron 52, 845–855 (2006).
Burrows, M. The Neurobiology of an Insect Brain (Oxford University Press, New York, 1996).
Chevaleyre, V. & Castillo, P.E. Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43, 871–881 (2004).
Yoshihara, M., Adolfsen, B., Galle, K.T. & Littleton, J.T. Retrograde signaling by Syt 4 induces presynaptic release and synapse-specific growth. Science 310, 858–863 (2005).
Tully, T. & Quinn, W.G. Classical conditioning and retention in normal and mutant Drosophila melanogaster. J. Comp. Physiol. [A] 157, 263–277 (1985).
Marin, E.C., Jefferis, G.S., Komiyama, T., Zhu, H. & Luo, L. Representation of the glomerular olfactory map in the Drosophila brain. Cell 109, 243–255 (2002).
Acknowledgements
We thank R. Axel, D. Reiff, G. Miesenböck, A. Ferrús and H. Nash for various fly stocks, L. Griffith for constructive suggestions, and W. Krause for assistance in functional optical imaging. This work was supported by US National Institutes of Health grant NS19904 to R.L.D. and the R. P. Doherty-Welch Chair in Science at the Baylor College of Medicine.
Author information
Authors and Affiliations
Contributions
X.L. carried out the experiments and analyzed the data. X.L. and R.L.D. designed the experiments and wrote the paper.
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figure 1 (PDF 4034 kb)
Rights and permissions
About this article
Cite this article
Liu, X., Davis, R. The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning. Nat Neurosci 12, 53–59 (2009). https://doi.org/10.1038/nn.2235
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.2235
This article is cited by
-
Multisensory learning binds neurons into a cross-modal memory engram
Nature (2023)
-
Unc13A and Unc13B contribute to the decoding of distinct sensory information in Drosophila
Nature Communications (2021)
-
Dopamine-based mechanism for transient forgetting
Nature (2021)
-
Untangling the wires: development of sparse, distributed connectivity in the mushroom body calyx
Cell and Tissue Research (2021)
-
A neural algorithm for Drosophila linear and nonlinear decision-making
Scientific Reports (2020)