A GABAergic Feedback Shapes Dopaminergic Input on the Drosophila Mushroom Body to Promote Appetitive Long-Term Memory.

Memory consolidation is a crucial step for long-term memory (LTM) storage. However, we still lack a clear picture of how memory consolidation is regulated at the neuronal circuit level. Here, we took advantage of the well-described anatomy of the Drosophila olfactory memory center, the mushroom body (MB), to address this question in the context of appetitive LTM. The MB lobes, which are made by the fascicled axons of the MB intrinsic neurons, are organized into discrete anatomical modules, each covered by the terminals of a defined type of dopaminergic neuron (DAN) and the dendrites of a corresponding type of MB output neuron (MBON). We previously revealed the essential role of one DAN, the MP1 neuron, in the formation of appetitive LTM. The MP1 neuron is anatomically matched to the GABAergic MBON MVP2, which has been attributed feedforward inhibitory functions recently. Here, we used behavior experiments and in vivo imaging to challenge the existence of MP1-MVP2 synapses and investigate their role in appetitive LTM consolidation. We show that MP1 and MVP2 neurons form an anatomically and functionally recurrent circuit, which features a feedback inhibition that regulates consolidation of appetitive memory. This circuit involves two opposite type 1 and type 2 dopamine receptors in MVP2 neurons and the metabotropic GABAB-R1 receptor in MP1 neurons. We propose that this dual-receptor feedback supports a bidirectional self-regulation of MP1 input to the MB. This mechanism displays striking similarities with the mammalian reward system, in which modulation of the dopaminergic signal is primarily assigned to inhibitory neurons.

Pavlowsky A ，Schor J ，Plaçais PY ，Preat T ... -  《-》

Reward signal in a recurrent circuit drives appetitive long-term memory formation.

Ichinose T ，Aso Y ，Yamagata N ，Abe A ，Rubin GM ，Tanimoto H ... -  《eLife》

A single GABAergic neuron mediates feedback of odor-evoked signals in the mushroom body of larval Drosophila.

Masuda-Nakagawa LM ，Ito K ，Awasaki T ，O'Kane CJ ... -  《Frontiers in Neural Circuits》

Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach.

Perisse E ，Owald D ，Barnstedt O ，Talbot CB ，Huetteroth W ，Waddell S ... -  《-》

Neural circuit mechanisms linking courtship and reward in Drosophila males.

Courtship has evolved to achieve reproductive success in animal species. However, whether courtship itself has a positive value remains unclear. In the present work, we report that courtship is innately rewarding and can induce the expression of appetitive short-term memory (STM) and long-term memory (LTM) in Drosophila melanogaster males. Activation of male-specific P1 neurons is sufficient to mimic courtship-induced preference and memory performance. Surprisingly, P1 neurons functionally connect to a large proportion of dopaminergic neurons (DANs) in the protocerebral anterior medial (PAM) cluster. The acquisition of STM and LTM depends on two distinct subsets of PAM DANs that convey the courtship-reward signal to the restricted regions of the mushroom body (MB) γ and α/β lobes through two dopamine receptors, D1-like Dop1R1 and D2-like Dop2R. Furthermore, the retrieval of STM stored in the MB α'/β' lobes and LTM stored in the MB α/β lobe relies on two distinct MB output neurons. Finally, LTM consolidation requires two subsets of PAM DANs projecting to the MB α/β lobe and corresponding MB output neurons. Taken together, our findings demonstrate that courtship is a potent rewarding stimulus and reveal the underlying neural circuit mechanisms linking courtship and reward in Drosophila males.

Shen P ，Wan X ，Wu F ，Shi K ，Li J ，Gao H ，Zhao L ，Zhou C ... -  《-》