Reward signal in a recurrent circuit drives appetitive long-term memory formation
- Tohoku University, Japan
- Max Planck Institute of Neurobiology, Germany
- Janelia Research Campus, Howard Hughes Medical Institute, United States
Figures
Figure 1 with 1 supplement
MBON-α1 receives inputs from MB-α1 and projects to the dendrites of PAM-α1.
(A–D) Anatomy of PAM-α1 (A, B) and MBON-α1 (C, D). Dotted line indicates α/β lobes in the mushroom body (MB) (A, C) or SMP, SIP, and SLP (superior medial, intermediate, and lateral protocerebra, …
Figure 1—figure supplement 1
MBON-α1 is neither GABAergic nor cholinergic.
Double labeling of the membrane of MBON-α1 (green) and anti-glutamic acid decarboxylase (GAD1) (A, magenta) or choline acetyltransferase (ChAT) (B, magenta). Arrowheads highlight some of the …
Figure 2 with 1 supplement
Processes of PAM-α1 and MBON-α1 intermingle each other.
(A) Double labeling of PAM-α1 and MBON-α1. PAM-α1 (magenta) and MBON-α1 (green) are visualized using R72D01-LexA and MB310C-GAL4, respectively. (B–D) Magnified substack images in SIP and SLP, …
Figure 2—figure supplement 1
Stereotyped projections of PAM-α1 and MBON-α1.
(A, C) Two additional examples of the double labeling confirm stereotypy of the projections. (B, D) Magnified substacks for the insets in (A) and (C), respectively. Scale bars, 10 µm.
Figure 3 with 1 supplement
Feedback from MBON-α1 is required for appetitive LTM formation.
(A) Diagram of the experiment. (B) Expression pattern of MB299B-GAL4. (C) Blockade of PAM-α1 does not impair STM significantly. 5-min appetitive memory was measured (n = 10, 10, 12). c: …
Figure 3—figure supplement 1
(A) Expression pattern of MB323B-GAL4.
Scale bar, 20 µm. (B) The LTM performance of MB310C/UAS-shi and MB323B/UAS-shi flies at the permissive temperature is not affected (n = 17, 16, 8, 9, 11). n.s.: p > 0.05.
Figure 4
NMDA receptors in PAM-α1 are required for appetitive LTM.
(A) The subunits of NMDA receptor are down-regulated in PAM-α1. (B, C) Knocking down NMDA receptor subunits does not impair 5-min memory (B: n = 16, 8, 13, 12, 13) but impairs 24-hr memory …
Figure 5
MBON-α1 signals reward for appetitive LTM.
(A) Activation of MBON-α1 was paired with odor presentations and 24-hr memory was measured. (B) Activation of MBON-α1 induces appetitive LTM formation (n = 16, 24, 24). Bar graphs are mean ± s.e.m. …
Figure 6 with 1 supplement
α/β KCs receive dopamine signals through DopR1 for LTM formation.
(A) Knocking down DopR1 in α/β Kenyon cells (KCs) but not in MBON-α1 impairs appetitive LTM (n = 17, 10, 11, 11, 18, 12, 7, 12, 27). (B) KC expression of DopR1 in the dumb2 mutant background fully …
Figure 6—figure supplement 1
(A) Expression pattern of MB008B-GAL4.
Scale bar, 20 µm. (B) Knocking down DopR1 in α/β KCs or MBON-α1 does not impair appetitive STM, suggesting normal sugar or odor perception of these flies (n = 7, 7, 12, 10, 10, 10, 9, 9, 22). Bar …
Figure 7 with 1 supplement
Output of α/β KCs has an essential role in the acquisition of appetitive LTM.
(A) Blockade of α/β KCs does not impair STM significantly (n = 8, 7, 7, 8, 9). (B) Blockade of α/β KCs during conditioning impairs LTM (n = 7, 7, 18, 19, 20). Bar graphs are mean ± s.e.m. *: p < …
Figure 7—figure supplement 1
Training and testing c739/UAS-shi and MB008B/UAS-shi flies at the permissive temperature do not impair appetitive LTM (n = 7, 6, 8, 9, 6).
Bar graphs are mean ± s.e.m. n.s.: p > 0.05.
Figure 8
Appetitive LTM is read out through MBON-α1.
(A) Blocking MBON-α1 during test impairs appetitive LTM retrieval (n = 20, 21, 11, 13, 20). (B) Blocking PAM-α1 during test does not significantly impair LTM retrieval (n = 7, 7, 10). Bar graphs are …
Figure 9
Dopamine release from PAM-α1 is required for appetitive LTM consolidation.
(A, C, E) Blocking PAM-α1 (A), MBON-α1 (C), or α/β−KC (E) for 1 hr immediately after conditioning impairs appetitive LTM (n = 16, 15, 22 (A); n = 15, 16, 14, 20, 34 (C); n = 9, 8, 10, 7, 15 (E)). (B,…
Figure 10 with 1 supplement
LTM specificity is compromised.
(A) Chemical structures of odorants. (B) Design of the experiment. For one group, presentation of 4-methylcyclohexanol was paired with sugar reward. The reciprocal group received sugar without odor. …
Figure 10—figure supplement 1
LTM is less specific with another pair of odors.
(A) Chemical structures of odorants. (B, C) The performance declined more sharply in STM (B: n = 20 for each) than in LTM (C: n = 20 for each) also with this odor pair. Each group was compared to …
Figure 11
Recurrent reward circuit drives appetitive LTM formation.
Feedback circuit model of appetitive LTM formation. Neuronal signal of a sugar reward mediated by PAM-α1 converges with olfactory information in the α/β KCs. The coincidental signal is read out …
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