GABAergic innervation and learning: the APL hypothesis

Luigi Prisco1, Philipp Ranft1, Gaia Tavosanis2

1 Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), 53127 Bonn (DE)
2 Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), 53127 Bonn (DE), LIMES institut, University of Bonn

In insects as in mammals, the neurotransmitter γ-amino-butyric acid (GABA) plays important roles in many cognitive processes, including learning and memory. The Drosophila anterior paired lateral (APL) neurons are two GABAergic neurons innervating the entire ipsilateral mushroom body, the olfactory memory centre of the fly brain. Odour exposure causes APL depolarization, and inhibition of the latter impairs the mushroom body´s typical sparse odour representation as well as the ability of the fly to discriminate between similar odours. Notably, reduction of GABA synthesis via APL enhances the ability of the fly to form memory, opening a series of questions regarding the neuron´s role in olfactory input processing and learning. We suggest a role of the APL neuron as odour-responses normalizer at the calyx, the mushroom body´s main input region. Using 2-photon in vivo Ca2+ imaging we show that APL responds with different levels of activity to different odours. Odours that generate a strong response in the second order neurons delivering information to the calyx lead to a stronger inhibition by APL, thus normalizing the strength of the input signal to the Mushroom Body neurons. We propose that this step is essential for the generation of a unique and sparse odour code in the mushroom body.