Rewarding Capacity of Optogenetically Activating a Giant GABAergic Central-Brain Interneuron in Larval Drosophila.

Larvae of the fruit fly Drosophila melanogaster are a powerful study case for understanding the neural circuits underlying behavior. Indeed, the numerical simplicity of the larval brain has permitted the reconstruction of its synaptic connectome, and genetic tools for manipulating single, identified neurons allow neural circuit function to be investigated with relative ease and precision. We focus on one of the most complex neurons in the brain of the larva (of either sex), the GABAergic anterior paired lateral neuron (APL). Using behavioral and connectomic analyses, optogenetics, Ca2+ imaging, and pharmacology, we study how APL affects associative olfactory memory. We first provide a detailed account of the structure, regional polarity, connectivity, and metamorphic development of APL, and further confirm that optogenetic activation of APL has an inhibiting effect on its main targets, the mushroom body Kenyon cells. All these findings are consistent with the previously identified function of APL in the sparsening of sensory representations. To our surprise, however, we found that optogenetically activating APL can also have a strong rewarding effect. Specifically, APL activation together with odor presentation establishes an odor-specific, appetitive, associative short-term memory, whereas naive olfactory behavior remains unaffected. An acute, systemic inhibition of dopamine synthesis as well as an ablation of the dopaminergic pPAM neurons impair reward learning through APL activation. Our findings provide a study case of complex circuit function in a numerically simple brain, and suggest a previously unrecognized capacity of central-brain GABAergic neurons to engage in dopaminergic reinforcement.SIGNIFICANCE STATEMENT The single, identified giant anterior paired lateral (APL) neuron is one of the most complex neurons in the insect brain. It is GABAergic and contributes to the sparsening of neuronal activity in the mushroom body, the memory center of insects. We provide the most detailed account yet of the structure of APL in larval Drosophila as a neurogenetically accessible study case. We further reveal that, contrary to expectations, the experimental activation of APL can exert a rewarding effect, likely via dopaminergic reward pathways. The present study both provides an example of unexpected circuit complexity in a numerically simple brain, and reports an unexpected effect of activity in central-brain GABAergic circuits.

Spatial distribution of the full-length members of the Grg family during embryonic neurogenesis reveals a "Grg-mediated repression map" in the mouse telencephalon.

The full-length members of the Groucho/Transducin-like Enhancer of split gene family, namely Grg1-4, encode nuclear corepressors that act either directly, via interaction with transcription factors, or indirectly by modifying histone acetylation or chromatin structure. In this work we describe a detailed expression analysis of Grg1-4 family members during embryonic neurogenesis in the developing murine telencephalon. Grg1-4 presented a unique, complex yet overlapping expression pattern; Grg1 and Grg3 were mainly detected in the proliferative zones of the telencephalon, Grg2 mainly in the subpallium and finally, Grg4 mainly in the subpallial post mitotic neurons. In addition, comparative analysis of the expression of Grg1-4 revealed that, at these stages, distinct telencephalic progenitor domains or structures are characterized by the presence of different combinations of Grg repressors, thus forming a "Grg-mediated repression map".