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Science 20 December 1996:
Vol. 274. no. 5295, pp. 2104 - 2107
DOI: 10.1126/science.274.5295.2104
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Reports

Associative Learning Disrupted by Impaired Gs Signaling in Drosophila Mushroom Bodies

John B. Connolly, * Ian J. H. Roberts, J. Douglas Armstrong, Kim Kaiser, Michael Forte, Tim Tully, Cahir J. O'Kane

Disruptions in mushroom body (MB) or central complex (CC) brain structures impair Drosophila associative olfactory learning. Perturbations in adenosine 3',5' monophosphate signaling also disrupt learning. To integrate these observations, expression of a constitutively activated stimulatory heterotrimeric guanosine triphosphate-binding protein alpha  subunit (Galpha s*) was targeted to these brain structures. The ability to associate odors with electroshock was abolished when Galpha s* was targeted to MB, but not CC, structures, whereas sensorimotor responses to these stimuli remained normal. Expression of Galpha s* did not affect gross MB morphology, and wild-type Galpha s expression did not affect learning. Thus, olfactory learning depends on regulated Gs signaling in Drosophila MBs.

J. B. Connolly, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA, and Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
I. J. H. Roberts and C. J. O'Kane. Department of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
J. D. Armstrong and K. Kaiser, Division of Molecular Genetics, Institute of Biomedical and Life Sciences, Pontecorvo Building, University of Glasgow, Glasgow, G11 6NU, UK.
M. Forte, Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, 3181 Southwestern Sam Jackson Park Road, Portland, OR 97201, USA.
T. Tully, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
*   To whom correspondence should be addressed. E-mail: connollj{at}cshl.org

Associative learning can be analyzed on biochemical, neuroanatomical, and behavioral levels. Perturbations in adenosine 3',5' monophosphate (cAMP) signaling affect learning in Aplysia, Drosophila, and mice (1-3). Gene disruptions of dunce (cAMP phosphodiesterase II), rutabaga [type I adenylyl cyclase (AC)], and the DC0 catalytic and RI regulatory subunits of cAMP-dependent protein kinase (PKA) impair olfactory learning in flies (2, 3). Neuroanatomically, Dunce, Rutabaga, and DC0 proteins are expressed throughout the brain but are expressed at elevated levels in the MBs (3, 4). Chemical ablation of the MBs, as well as mutations disrupting either MB or CC structures, produce defective olfactory learning (5, 6). No functional data, however, indicate that cAMP signaling within the MBs or CC mediates this type of learning.

To explore this notion, we restricted disruption of the cAMP pathway to the MBs or CC and examined the effects on olfactory learning. We used the P-GAL4 enhancer trap system to target expression of Galpha s transgenes within the brain (7-9). Upon receptor activation, Galpha s binds guanosine triphosphate (GTP) and becomes activated, effecting AC stimulation (10). The GTPase activity of Galpha s hydrolyzes GTP to guanosine diphosphate (GDP), deactivating Galpha s. The Gln215 rightarrow  Leu215 (Q215L) mutation in Drosophila Galpha s impairs this GTPase activity and results in a form of Galpha s (Galpha s*), which constitutively activates AC (9, 10). Transgenic flies capable of expressing either wild-type Galpha s (Galpha sWT) or Galpha s* under the control of the GAL4-responsive upstream activating sequence (UAS) were generated (11). Expression of these transgenes was driven by selected P-GAL4 insertions that demonstrated prominent expression in the MBs or CC (12).

To examine associative learning in these flies, a Pavlovian olfactory conditioning assay was used (13). In that procedure, flies are trained by exposure to electroshock paired with one odor [octanol (OCT) or methylcyclohexanol (MCH)] and subsequent exposure to a second odor without electroshock. Immediately after training, learning is measured by forcing flies to choose between the two odors used during training. No preference between odors results in a performance index (PI) of zero (no learning), as is the case for naive flies. Avoidance of the odor previously paired with electroshock, however, yields a PI > 0 (with a score of 100 indicating maximal learning).

When Galpha s* was expressed in MBs by each of three P-GAL4 insertions (238Y, C309, and C747), learning was completely abolished (Fig. 1, A through C). When a fourth MB-expressing P-GAL4 insertion (201Y) was used, expression of Galpha s* reduced learning by sim 50% (Fig. 1D). In contrast, expression of wild-type Galpha s in each of these four P-GAL4 lines had no effect on learning (Fig. 1, A through D). Thus, learning deficits resulted from the Q215L mutation constitutively activating Galpha s* and not simply from misregulation of endogenous signaling by Galpha s overexpression (9).


Fig. 1. Associative learning is disrupted by expression of activated but not wild-type Galpha s. All behavioral experiments were performed blind with respect to genotype. Flies of the Canton-S strain served as a wild-type control for the calibration of teaching machines. Potential genetic background effects dictated that the appropriate controls were those for which flies with either the P-GAL4 or UAS-Galpha s insertions were heterozygous. After assays of associative learning, PIs were calculated as described in (25). Bars represent mean PIs ± SEMs; numbers above each bar indicate number of PIs per group. In (A) through (D) (mushroom bodies), the symbols below the bars are as follows: + represents a Canton-S chromosome, G* represents an insertion of UAS-Galpha s*, G1 represents UAS-Galpha sWT1, G2 represents UAS-Galpha sWT2, and P represents the P-GAL4 insertion [insertion numbers are specified in boxes above (A) through (D)]. Hence, only P/G* flies expressed Galpha s*. For each of the P-GAL4 lines 238Y, C309, C747, and 201Y, a one-way analysis of variance (ANOVA) of PIs from all genotypes revealed significant differences. For each P-GAL4 insertion, P/G* was compared with both P/+ and G*/+, P/G1 was compared with both P/+ and G1/+, P/G2 was compared with both P/+ and G2/+, and P/G* was also compared with both P/G1 and P/G2, producing a total of eight planned pairwise comparisons. To maintain an error rate of alpha  = 0.05 in the experiment, the critical P value was adjusted to alpha  = 0.006 (26). In each case, an asterisk above any group indicates significant differences from all other groups (except in 238Y, where P/G2 was significantly different from P/+ but not from G2/+). In (E) and (F) (central complex), the symbols below the bars are as defined in (A) through (D). For each of the P-GAL4 lines C232 and OK348, PIs from all groups were subjected to a one-way ANOVA, and P/G* was compared with P/+ and G*/+, producing two planned pairwise comparisons. To maintain an error rate of alpha  = 0.05 in the experiment, the critical P value was adjusted to alpha  = 0.025 (26). In both cases, no significant differences were detected. [View Larger Versions of these Images (41K GIF file)]

In these four learning-impaired lines, olfactory responses to OCT and MCH were normal. Likewise, responses to electroshock were normal (Table 1). This demonstrates that expression of Galpha s* did not affect naive sensorimotor responses to electroshock or odors. Thus, all MB P-GAL4 lines expressing Galpha s*, which showed normal sensorimotor responses, showed learning defects (14). When Galpha s* was expressed in the ellipsoid body or fan-shaped body of the CC (with the use of P-GAL4 C232 or OK348, respectively) (Fig. 2, E and F), learning was unaffected (Fig. 1, E and F). This suggests that such perturbation of Gs signaling in the CC is insufficient to disrupt olfactory learning (15).

Table 1. Olfactory acuity and shock reactivity are normal in P-GAL4 lines expressing Galpha s* in the MBs. Symbols in the left-hand column are as defined in the legend of Fig. 1. In each case, n = 8, except n = 6 for G*/+ in the 238Y MCH 10-2 experiment. Olfactory acuity tests with odors at the concentrations used during training and testing (100 dilution) and at 10-2 dilutions were performed, and PIs were calculated as described in (25). For each P-GAL4 line, PIs from four genotypes (+/+, G*/+, P/+, and P/G*) and four odor levels (OCT 100, OCT 10-2, MCH 100, and MCH 10-2) were subjected to a two-way ANOVA, with genotype and odor level as main effects and genotype × odor level as the interaction term. For each P-GAL4 insertion, P/G* was compared with P/+ and G*/+ heterozygous controls at each of the four odor levels, producing a total of eight pairwise planned comparisons. To maintain an error rate of alpha  = 0.05 in the experiment, the critical P value was adjusted to alpha  = 0.006 (26). In no case were significant differences detected. Shock reactivity tests to the training voltage (60 V) and to 20 V were performed as described in (28). For each P-GAL4 line, PIs from four genotypes (+/+, G*/+, P/+, and P/G*) and two shock groups (60 and 20 V) were subjected to a two-way ANOVA, with genotype and shock group as main effects and genotype × shock group as the interaction term. For each P-GAL4 insertion, P/G* was compared with P/+ and G*/+ heterozygous controls for both shock groups, producing a total of four pairwise planned comparisons. To maintain an error rate of alpha  = 0.05 in the experiment, the critical P value was adjusted to alpha  = 0.013 (26). In no case were significant differences detected.

Lines and genotypes Olfactory acuity
OCT dilution
 MCH dilution
 Shock reactivity
100 10-2 100 10-2 60 V 20 V
201 Y
+/+ 66  ±  5 44  ±  8 62  ±  5 35  ±  5 93  ±  2 59  ±  6
G*/+ 69  ±  4 40  ±  8 70  ±  4 40  ±  7 87  ±  2 48  ±  8
P/+ 70  ±  5 37  ±  5 67  ±  3 30  ±  5 89  ±  1 49  ±  9
P/G* 61  ±  6 44  ±  7 70  ±  6 32  ±  5 86  ±  2 46  ±  6
238Y
+/+ 53  ±  4 28  ±  3 63  ±  3 22  ±  2 84  ±  3 25  ±  6
G*/+ 58  ±  5 28  ±  3 68  ±  4 28  ±  2 75  ±  2 24  ±  4
P/+ 63  ±  4 29  ±  4 71  ±  5 24  ±  3 77  ±  5 31  ±  5
P/G* 64  ±  5 17  ±  8 67  ±  4 21  ±  4 73  ±  3 25  ±  8
C309
+/+ 64  ±  4 32  ±  7 58  ±  4 26  ±  4 84  ±  3 32  ±  7
G*/+ 61  ±  3 29  ±  4 63  ±  3 21  ±  3 75  ±  2 26  ±  3
P/+ 65  ±  4 32  ±  5 67  ±  4 25  ±  4 72  ±  4 31  ±  5
P/G* 62  ±  3 32  ±  8 66  ±  5 27  ±  5 66  ±  6 25  ±  6
C747
+/+ 53  ±  4 28  ±  3 63  ±  3 22  ±  2 84  ±  3 25  ±  6
G*/+ 60  ±  5 27  ±  3 70  ±  3 26  ±  5 73  ±  3 22  ±  4
P/+ 59  ±  4 28  ±  5 71  ±  4 30  ±  4 77  ±  3 24  ±  4
P/G* 54  ±  2 35  ±  3 76  ±  3 28  ±  2 68  ±  3 21  ±  4

Fig. 2. P-GAL4 expression patterns in adult brains. In all cases, brains were examined as whole mounts. In panel i in (A) through (D) and in (E) and (F), brains from P-GAL4 lines crossed to UAS-GFPB1 (GFP81, green fluorescent protein, insertion B1) were examined under fluorescence microscopy (26). In panels ii and iii in (A) through (D), GAL4-dependent beta -Gal expression patterns were visualized immunohistochemically (17). In (G) and (H), brains were stained with X-Gal (5-bromo-4-chloro-3-indol-beta -D-galactosidase) (20). In panels showing mushroom bodies, (A) shows line 238Y, (B) shows line C309, (C) shows line C747, and (D) shows line 201Y. In panel i of (A), ol indicates optic lobes and tg indicates the thoracic ganglion. The predominant site of expression in lines 238Y, C309, C747, and 201Y was in the MBs. All lines labeled small neuronal subsets in the thoracic ganglion. Panel ii of (A) through (D) shows a three-dimensional confocal reconstruction from a frontal aspect. For clarity, the Kenyon cell body layer of each pattern has been excluded. In lines 238Y, C309, and C747, the alpha , beta , and gamma  lobes (labeled) of the MBs stained strongly, except that C309 showed less in the core regions of the alpha  and beta  lobes (17). In line 201Y, the MB gamma  lobe was extensively stained, but only narrow core elements of the alpha  and beta  lobes showed staining. All lines in (A) through (D) also stained in the pars intercerebralis (p). In line 238Y, a small number of extrinsic neurons arborizing in the gamma  lobe and neurons spanning the optic lobes, which sent large horizontal tracts to the contralateral lobe and branches to the lateral protocerebrum, were revealed. CC neurons innervating narrow layers of the fan-shaped body and noduli, and a small number of antennal lobe (al) afferents, were weakly stained. In line C309, several classes of optic lobe neurons, a small set of antennal lobe local interneurons, and CC neurons (a subset of the ellipsoid body and fan-shaped body) stained weakly. In line C747, antennal lobe local interneurons were labeled. CC neurons with arbors in the protocerebral bridge, superior arch of the fan-shaped body, ellipsoid body, and noduli stained, which did not appear to overlap with those of 238Y and C309. Large numbers of optic lobe neurons stained, with dense regions of arborization in the medulla. In line 201Y, two lateral neurons resembling MB feedback interneurons were labeled. Panel iii of (A) through (D) shows the MB Kenyon cell body (k) layer. Line 238Y expressed beta -Gal in Kenyon cell bodies. Line C747 (12, 17) stained more strongly a subset of Kenyon cells similar to those of C309. Line 201Y showed weak expression in a diffuse subset of cell bodies. In panels showing the central complex, (E) shows line C232 (18). GFP was detected in cell bodies (ce) and the neuropil (e) of the ellipsoid body. (F) shows line OK348. GFP was detected in cell bodies (not shown) and the neuropil (f) of the fan-shaped body. In panels showing gross morphology (20), brains from lines C309/UAS-lacZ (G) and C309/UAS-lacZ/UAS-Galpha s* (H) are shown. Scale bar in panel i of (A), 50 µm (applies to all i panels); in panel ii of (A), 20 µm (applies to all ii and iii panels); in (E), 50 µm [also applies to (F)]; and in (G), 50 µm [also applies to (H)]. [View Larger Version of this Image (116K GIF file)]

The expression patterns of MB P-GAL4 lines were examined with confocal microscopy after immunolocalization of expression of the GAL4-driven beta -galactosidase (beta -Gal) reporter gene (16-18) (Fig. 2, A through D). In lines 238Y, C309, and C747, where learning was abolished with Galpha s* expression, extensive expression in all MB lobes was evident. In line 201Y, which yielded a partial learning defect with Galpha s* expression, the gamma  lobe stained extensively, whereas only narrow core elements of the alpha  and beta  lobes were labeled (17, 18). All MB-expressing lines showed GAL4 activity elsewhere in the brain. Optic lobe structural mutants learn normally, which suggests that Galpha s* expression in the optic lobes did not affect learning (5). Within the central brain, the MBs and pars intercerebralis were the only common regions of expression in all learning-impaired lines. Although we cannot exclude a role for the pars intercerebralis in olfactory learning, this structure has not been implicated previously in the process. By contrast, chemical ablation of the MBs is sufficient to abolish olfactory learning (6, 15).

Pan-neural expression of Galpha s* during development produced neither lethality nor overt behavioral phenotypes, which suggests that perturbation of Gs signaling did not significantly affect basic neuronal function (19). Furthermore, gross morphology appeared normal when Galpha s* and beta -Gal were coexpressed in the MBs (20) (Fig. 2, G and H). These data suggest that the abolition of learning did not result from maldevelopment of underlying structures. Admittedly, more subtle, undetected changes in MB structure might contribute to learning defects, but chemical ablation experiments show that >96% of MBs must be absent to produce PIs below 20 (6). In contrast, PIs of zero were obtained here with no detectable effect on MB morphology.

We have presented in vivo evidence that associative olfactory learning in Drosophila requires regulated Gs signaling within MB neurons. MB expression of Galpha s* can abolish associative learning, whereas null alleles of dunce and rutabaga exhibit only partial impairments. The dunce and rutabaga mutations affect only one class of phosphodiesterase or AC, respectively. In flies, three ACs, in addition to Rutabaga, have been identified (21). In mammals, Galpha s stimulates all ACs to some degree (22). Thus, disruption of all AC regulation by Galpha s* expression could have more drastic effects on signaling than removal of one form of AC (as in rutabaga) or cyclic nucleotide phosphodiesterase (as in dunce). Alternatively, activation of PKA-dependent phosphorylation through Galpha s* expression could impede modulatory changes in shared substrates or cellular systems by kinases other than PKA. Another possibility is that Galpha s could exert signaling effects other than through the cAMP pathway, such as through direct modulation of channels (23). In such a scenario, Galpha s* expression might also produce learning deficits greater than those observed in dunce or rutabaga mutants. Further analyses of Gs signaling in Drosophila should clarify these issues.

REFERENCES AND NOTES

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  20. The P-GAL4 C309 line was crossed to UAS-lacZ and UAS-lacZ;UAS-Galpha s* lines. Brains from the resultant progeny were dissected, and beta -Gal activity was detected as described [ S. T. Sweeney, K. Broadie, J. Keane, H. Niemann, C. J. O'Kane, Neuron 14, 341 (1995) [Medline]].
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  29. We thank K. Moffat, J. Keane, K. Störtkuhl, R. Greenspan, M. Yang, G. Boulianne, and A. Brand for reagents. Supported by grants from the Wellcome Trust and the Science and Engineering Research Council (GR/F94989) (to C.J.O'K.), the Human Frontiers Science program (to C.J.O'K., K.K., and M.F.), and NIH grant HD 32245 (to T.T.).

3 June 1996; accepted 21 October 1996


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   Abstract »    Full Text »    PDF »
Differential microarray analysis of Drosophila mushroom body transcripts using chemical ablation.
M. Kobayashi, L. Michaut, A. Ino, K. Honjo, T. Nakajima, Y. Maruyama, H. Mochizuki, M. Ando, I. Ghangrekar, K. Takahashi, et al. (2006)
PNAS 103, 14417-14422
   Abstract »    Full Text »    PDF »
Context and occasion setting in Drosophila visual learning..
B. Brembs and J. Wiener (2006)
Learn. Mem. 13, 618-628
   Abstract »    Full Text »    PDF »
Behavioral Responses to Odorants in Drosophila Require Nervous System Expression of the {beta} Integrin Gene Myospheroid.
P. Bhandari, J. W. Gargano, M. M. Goddeeris, and M. S. Grotewiel (2006)
Chem Senses 31, 627-639
   Abstract »    Full Text »    PDF »
Roles for Drosophila mushroom body neurons in olfactory learning and memory.
D.-B. G. Akalal, C. F. Wilson, L. Zong, N. K. Tanaka, K. Ito, and R. L. Davis (2006)
Learn. Mem. 13, 659-668
   Abstract »    Full Text »    PDF »
Gsalpha is involved in sugar perception in Drosophila melanogaster..
K. Ueno, S. Kohatsu, C. Clay, M. Forte, K. Isono, and Y. Kidokoro (2006)
J. Neurosci. 26, 6143-6152
   Abstract »    Full Text »    PDF »
Drosophila Eph receptor guides specific axon branches of mushroom body neurons.
M. Boyle, A. Nighorn, and J. B. Thomas (2006)
Development 133, 1845-1854
   Abstract »    Full Text »    PDF »
Steroid hormone-dependent transformation of polyhomeotic mutant neurons in the Drosophila brain.
J. Wang, C.-H. J. Lee, S. Lin, and T. Lee (2006)
Development 133, 1231-1240
   Abstract »    Full Text »    PDF »
Cholinergic Synaptic Transmission in Adult Drosophila Kenyon Cells In Situ.
H. Gu and D. K. O'Dowd (2006)
J. Neurosci. 26, 265-272
   Abstract »    Full Text »    PDF »
Stereotypic and random patterns of connectivity in the larval mushroom body calyx of Drosophila.
L. M. Masuda-Nakagawa, N. K. Tanaka, and C. J. O'Kane (2005)
PNAS 102, 19027-19032
   Abstract »    Full Text »    PDF »
Inaugural Article: Functional analysis of fruitless gene expression by transgenic manipulations of Drosophila courtship.
A. Villella, S. L. Ferri, J. D. Krystal, and J. C. Hall (2005)
PNAS 102, 16550-16557
   Abstract »    Full Text »    PDF »
An Aplysia Type 4 Phosphodiesterase Homolog Localizes at the Presynaptic Terminals of Aplysia Neuron and Regulates Synaptic Facilitation.
H. Park, J.-A Lee, C. Lee, M.-J. Kim, D.-J. Chang, H. Kim, S.-H. Lee, Y.-S. Lee, and B.-K. Kaang (2005)
J. Neurosci. 25, 9037-9045
   Abstract »    Full Text »    PDF »
Induction of cAMP Response Element-Binding Protein-Dependent Medium-Term Memory by Appetitive Gustatory Reinforcement in Drosophila Larvae.
K. Honjo and K. Furukubo-Tokunaga (2005)
J. Neurosci. 25, 7905-7913
   Abstract »    Full Text »    PDF »
Experiential Effects of Appetitive and Nonappetitive Odors on Feeding Behavior in the Blowfly, Phormia regina: A Putative Role for Tyramine in Appetite Regulation.
T. Nisimura, A. Seto, K. Nakamura, M. Miyama, T. Nagao, S. Tamotsu, R. Yamaoka, and M. Ozaki (2005)
J. Neurosci. 25, 7507-7516
   Abstract »    Full Text »    PDF »
Drosophila Mushroom Body Kenyon Cells Generate Spontaneous Calcium Transients Mediated by PLTX-Sensitive Calcium Channels.
S. A. Jiang, J. M. Campusano, H. Su, and D. K. O'Dowd (2005)
J Neurophysiol 94, 491-500
   Abstract »    Full Text »    PDF »
Requirement of Cul3 for Axonal Arborization and Dendritic Elaboration in Drosophila Mushroom Body Neurons.
S. Zhu, R. Perez, M. Pan, and T. Lee (2005)
J. Neurosci. 25, 4189-4197
   Abstract »    Full Text »    PDF »
Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila.
N. Agrawal, J. Pallos, N. Slepko, B. L. Apostol, L. Bodai, L.-W. Chang, A.-S. Chiang, L. M. Thompson, and J. L. Marsh (2005)
PNAS 102, 3777-3781
   Abstract »    Full Text »    PDF »
An Increased Receptive Field of Olfactory Receptor Or43a in the Antennal Lobe of Drosophila Reduces Benzaldehyde-driven Avoidance Behavior.
K. F. Stortkuhl, R. Kettler, S. Fischer, and B. T. Hovemann (2005)
Chem Senses 30, 81-87
   Abstract »    Full Text »    PDF »
Drosophila Short Neuropeptide F Regulates Food Intake and Body Size.
K.-S. Lee, K.-H. You, J.-K. Choo, Y.-M. Han, and K. Yu (2004)
J. Biol. Chem. 279, 50781-50789
   Abstract »    Full Text »    PDF »
Plasticity in the Olfactory System: Lessons for the Neurobiology of Memory.
D. A. Wilson, A. R. Best, and R. M. Sullivan (2004)
Neuroscientist 10, 513-524
   Abstract »    PDF »
Stereotyped Odor-Evoked Activity in the Mushroom Body of Drosophila Revealed by Green Fluorescent Protein-Based Ca2+ Imaging.
Y. Wang, H.-F. Guo, T. A. Pologruto, F. Hannan, I. Hakker, K. Svoboda, and Y. Zhong (2004)
J. Neurosci. 24, 6507-6514
   Abstract »    Full Text »    PDF »
Learning and Memory Deficits Upon TAU Accumulation in Drosophila Mushroom Body Neurons.
A. Mershin, E. Pavlopoulos, O. Fitch, B. C. Braden, D. V. Nanopoulos, and E. M.C. Skoulakis (2004)
Learn. Mem. 11, 277-287
   Abstract »    Full Text »    PDF »
Dissecting the pathological effects of human A{beta}40 and A{beta}42 in Drosophila: A potential model for Alzheimer's disease.
K. Iijima, H.-P. Liu, A.-S. Chiang, S. A. Hearn, M. Konsolaki, and Y. Zhong (2004)
PNAS 101, 6623-6628
   Abstract »    Full Text »    PDF »
TARGETing "When" and "Where".
Y. Wang and Y. Zhong (2004)
Sci. STKE 2004, pe5
   Abstract »    Full Text »    PDF »
Molecular and Comparative Genetics of Mental Retardation.
J. K. Inlow and L. L. Restifo (2004)
Genetics 166, 835-881
   Abstract »    Full Text »    PDF »
Pharmacogenetic rescue in time and space of the rutabaga memory impairment by using Gene-Switch.
Z. Mao, G. Roman, L. Zong, and R. L. Davis (2004)
PNAS 101, 198-203
   Abstract »    Full Text »    PDF »
Motor output reflects the linear superposition of visual and olfactory inputs in Drosophila.
M. A. Frye and M. H. Dickinson (2004)
J. Exp. Biol. 207, 123-131
   Abstract »    Full Text »    PDF »
Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila.
M. Schwaerzel, M. Monastirioti, H. Scholz, F. Friggi-Grelin, S. Birman, and M. Heisenberg (2003)
J. Neurosci. 23, 10495-10502
   Abstract »    Full Text »    PDF »
Fast Synaptic Currents in Drosophila Mushroom Body Kenyon Cells Are Mediated by {alpha}-Bungarotoxin-Sensitive Nicotinic Acetylcholine Receptors and Picrotoxin-Sensitive GABA Receptors.
H. Su and D. K. O'Dowd (2003)
J. Neurosci. 23, 9246-9253
   Abstract »    Full Text »    PDF »
Development of the Drosophila mushroom bodies: elaboration, remodeling and spatial organization of dendrites in the calyx.
S. Zhu, A.-S. Chiang, and T. Lee (2003)
Development 130, 2603-2610
   Abstract »    Full Text »    PDF »
Mutation and Activation of Galpha s Similarly Alters Pre- and Postsynaptic Mechanisms Modulating Neurotransmission.
R. B. Renden and K. Broadie (2003)
J Neurophysiol 89, 2620-2638
   Abstract »    Full Text »    PDF »
Embryonic and larval development of the Drosophila mushroom bodies: concentric layer subdivisions and the role of fasciclin II.
M. Kurusu, T. Awasaki, L. M. Masuda-Nakagawa, H. Kawauchi, K. Ito, and K. Furukubo-Tokunaga (2003)
Development 129, 409-419
   Abstract »    Full Text »    PDF »
Working memory and fear conditioning.
R. M. Carter, C. Hofstotter, N. Tsuchiya, and C. Koch (2003)
PNAS 100, 1399-1404
   Abstract »    Full Text »    PDF »
Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila.
Y. H. Belgacem and J.-R. Martin (2002)
PNAS 99, 15154-15158
   Abstract »    Full Text »    PDF »
Functional Dissection of Neuroanatomical Loci Regulating Ethanol Sensitivity in Drosophila.
A. R. Rodan, J. A. Kiger Jr, and U. Heberlein (2002)
J. Neurosci. 22, 9490-9501
   Abstract »    Full Text »    PDF »
Conditional disruption of synaptic transmission induces male-male courtship behavior in Drosophila.
T. Kitamoto (2002)
PNAS 99, 13232-13237
   Abstract »    Full Text »    PDF »
Electrophysiological Analysis of Synaptic Transmission in Central Neurons of Drosophila Larvae.
J. Rohrbough and K. Broadie (2002)
J Neurophysiol 88, 847-860
   Abstract »    Full Text »    PDF »
Choice Behavior of Drosophila Facing Contradictory Visual Cues.
S. Tang and A. Guo (2001)
Science 294, 1543-1547
   Abstract »    Full Text »    PDF »
Conditional Rescue of Olfactory Learning and Memory Defects in Mutants of the 14-3-3zeta Gene leonardo.
N. Philip, S. F. Acevedo, and E. M. C. Skoulakis (2001)
J. Neurosci. 21, 8417-8425
   Abstract »    Full Text »    PDF »
Genetic Analysis of the Drosophila Gs{{alpha}} Gene.
W. J. Wolfgang, A. Hoskote, I. J. H. Roberts, S. Jackson, and M. Forte (2001)
Genetics 158, 1189-1201
   Abstract »    Full Text »    PDF »
Foraging Behaviour in Drosophila Larvae: Mushroom Body Ablation.
K. A. Osborne, J. S. de Belle, and M. B. Sokolowski (2001)
Chem Senses 26, 223-230
   Abstract »    Full Text »    PDF »
High Ethanol Consumption and Low Sensitivity to Ethanol-Induced Sedation in Protein Kinase A-Mutant Mice.
T. E. Thiele, B. Willis, J. Stadler, J. G. Reynolds, I. L. Bernstein, and G. S. McKnight (2000)
J. Neurosci. 20, RC75
   Abstract »    Full Text »    PDF »
The Genetic Variant Voila1 Causes Gustatory Defects during Drosophila Development.
M. Balakireva, N. Gendre, R. F. Stocker, and J.-F. Ferveur (2000)
J. Neurosci. 20, 3425-3433
   Abstract »    Full Text »    PDF »
Localization of a Short-Term Memory in Drosophila.
T. Zars, M. Fischer, R. Schulz, and M. Heisenberg (2000)
Science 288, 672-675
   Abstract »    Full Text »
Tissue-Specific Expression of a Type I Adenylyl Cyclase Rescues the rutabaga Mutant Memory Defect: In Search of the Engram.
T. Zars, R. Wolf, R. Davis, and M. Heisenberg (2000)
Learn. Mem. 7, 18-31
   Abstract »    Full Text »
Developmental Expression of an amn+ Transgene Rescues the Mutant Memory Defect of amnesiac Adults.
J. DeZazzo, S. Xia, J. Christensen, K. Velinzon, and T. Tully (1999)
J. Neurosci. 19, 8740-8746
   Abstract »    Full Text »    PDF »
OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons.
K. M. Campbell, L. de Lecea, D. M. Severynse, M. G. Caron, M. J. McGrath, S. B. Sparber, L.-Y. Sun, and F. H. Burton (1999)
J. Neurosci. 19, 5044-5053
   Abstract »    Full Text »    PDF »
Mapping of the Anatomical Circuit of CaM Kinase-Dependent Courtship Conditioning in Drosophila.
M.-l. A. Joiner and L. C. Griffith (1999)
Learn. Mem. 6, 177-192
   Abstract »    Full Text »
Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast.
T Lee, A Lee, and L Luo (1999)
Development 126, 4065-4076
   Abstract »    PDF »
loco encodes an RGS protein required for Drosophila glial differentiation.
S Granderath, A Stollewerk, S Greig, C. Goodman, C. O'Kane, and C Klambt (1999)
Development 126, 1781-1791
   Abstract »    PDF »
The Steroid Hormone 20-Hydroxyecdysone Enhances Neurite Growth of Drosophila Mushroom Body Neurons Isolated during Metamorphosis.
R. Kraft, R. B. Levine, and L. L. Restifo (1998)
J. Neurosci. 18, 8886-8899
   Abstract »    Full Text »    PDF »
A Novel Octopamine Receptor with Preferential Expression in Drosophila Mushroom Bodies.
K.-A. Han, N. S. Millar, and R. L. Davis (1998)
J. Neurosci. 18, 3650-3658
   Abstract »    Full Text »    PDF »
What Do the Mushroom Bodies Do for the Insect Brain? An Introduction.
M. Heisenberg (1998)
Learn. Mem. 5, 1-10
   Full Text »
Evolution, Discovery, and Interpretations of Arthropod Mushroom Bodies.
N. J. Strausfeld, L. Hansen, Y. Li, R. S. Gomez, and K. Ito (1998)
Learn. Mem. 5, 11-37
   Abstract »    Full Text »
The Organization of Extrinsic Neurons and Their Implications in the Functional Roles of the Mushroom Bodies in Drosophila melanogaster Meigen.
K. Ito, K. Suzuki, P. Estes, M. Ramaswami, D. Yamamoto, and N. J. Strausfeld (1998)
Learn. Mem. 5, 52-77
   Abstract »    Full Text »
Metamorphosis of the Mushroom Bodies; Large-Scale Rearrangements of the Neural Substrates for Associative Learning and Memory in Drosophila.
J. D. Armstrong, J. S. de Belle, Z. Wang, and K. Kaiser (1998)
Learn. Mem. 5, 102-114
   Abstract »    Full Text »
Dopamine and Mushroom Bodies in Drosophila: Experience-Dependent and -Independent Aspects of Sexual Behavior.
W. S. Neckameyer (1998)
Learn. Mem. 5, 157-165
   Abstract »    Full Text »
Drosophila Mushroom Bodies Are Dispensable for Visual, Tactile, and Motor Learning.
R. Wolf, T. Wittig, L. Liu, G. Wustmann, D. Eyding, and M. Heisenberg (1998)
Learn. Mem. 5, 166-178
   Abstract »    Full Text »
Mushroom Bodies Suppress Locomotor Activity in Drosophila melanogaster.
J.-R. Martin, R. Ernst, and M. Heisenberg (1998)
Learn. Mem. 5, 179-191
   Abstract »    Full Text »
Defective Learning in Mutants of the Drosophila Gene for a Regulatory Subunit of cAMP-Dependent Protein Kinase.
S. F. Goodwin, M. Del Vecchio, K. Velinzon, C. Hogel, S. R. H. Russell, T. Tully, and K. Kaiser (1997)
J. Neurosci. 17, 8817-8827
   Abstract »    Full Text »    PDF »
An activating mutation in a Caenorhabditis elegans Gs protein induces neural degeneration..
H C Korswagen, J H Park, Y Ohshima, and R H Plasterk (1997)
Genes & Dev. 11, 1493-1503
   Abstract »    PDF »
A Return to Genetic Dissection of Memory in Drosophila.
T. Tully, G. Bolwig, J. Christensen, J. Connolly, M. DelVecchio, J. DeZazzo, J. Dubnau, C. Jones, S. Pinto, M. Regulski, et al. (1996)
Cold Spring Harb Symp Quant Biol 61, 207-218
   Abstract »    PDF »
The Role of Drosophila Mushroom Body Signaling in Olfactory Memory.
S. E. McGuire, P. T. Le, and R. L. Davis (2001)
Science 293, 1330-1333
   Abstract »    Full Text »    PDF »
Type II cAMP-dependent Protein Kinase-deficient Drosophila Are Viable but Show Developmental, Circadian, and Drug Response Phenotypes.
S. K. Park, S. A. Sedore, C. Cronmiller, and J. Hirsh (2000)
J. Biol. Chem. 275, 20588-20596
   Abstract »    Full Text »    PDF »


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