Presynaptic Inhibition of Gamma Lobe Neurons Is Required for Olfactory Learning in Drosophila

Abstract

The loss of heterotrimeric G(o) signaling through the expression of pertussis toxin (PTX) within either the α/β or γ lobe mushroom body neurons of Drosophila results in the impaired aversive olfactory associative memory formation. Herein, we focus on the cellular effects of G(o) signaling in the γ lobe mushroom body neurons during memory formation. Expression of PTX in the γ lobes specifically inhibits G(o) activation, leading to poor olfactory learning and an increase in odor-elicited synaptic vesicle release. In the γ lobe neurons, training decreases synaptic vesicle release elicited by the unpaired conditioned stimulus -, while leaving presynaptic activation by the paired conditioned stimulus + unchanged. PTX expression in γ lobe neurons inhibits the generation of this differential synaptic activation by conditioned stimuli after negative reinforcement. Hyperpolarization of the γ lobe neurons or the inhibition of presynaptic activity through the expression of dominant negative dynamin transgenes ameliorated the memory impairment caused by PTX, indicating that the disinhibition of these neurons by PTX was responsible for the poor memory formation. The role for γ lobe inhibition, carried out by G(o) activation, indicates that an inhibitory circuit involving these neurons plays a positive role in memory acquisition. This newly uncovered requirement for inhibition of odor-elicited activity within the γ lobes is consistent with these neurons serving as comparators during learning, perhaps as part of an odor salience modification mechanism.

Dopaminergic Modulation of cAMP Drives Nonlinear Plasticity across the Drosophila Mushroom Body Lobes

“…In addition, stimulating MP1 dopaminergic neurons innervating the heel of the γ lobe is sufficient as an aversive reinforcer [17, 29]. Finally, learning induces plasticity in synaptic vesicle release from MB γ lobes, which depends in part on Gαo signaling [44]. Our data support a critical role for the γ lobe in short-term memory.…”

Trace Conditioning in Drosophila Induces Associative Plasticity in Mushroom Body Kenyon Cells and Dopaminergic Neurons

“…This may indicate either a difference between trace conditioning (this study) and standard conditioning (published data), or a difference in other experimental parameters that may also account for inconsistencies in the published effects of odor—shock conditioning (Zhang and Roman, 2013; Boto et al, 2014; Hige et al, 2015a). …”

“…However, the CS-US coincidence detection mechanism in trace conditioning is unknown (Galili et al, 2011; Shuai et al, 2011; Dylla et al, 2013). In standard conditioning the CS-induced increase in KCs' calcium concentration coincides with the US-(dopamine)-induced second messengers, which is thought to synergistically activate the rutabaga adenylyl cyclase (Duerr and Quinn, 1982; Dudaí et al, 1983; Tomchik and Davis, 2009; Gervasi et al, 2010), and ultimately alters the strength of KC-to-MBON synapses (Dubnau et al, 2001; McGuire et al, 2001; Schwaerzel et al, 2003; Séjourné et al, 2011; Pai et al, 2013; Zhang and Roman, 2013; Aso et al, 2014b; Bouzaiane et al, 2015; Cohn et al, 2015; Hige et al, 2015a; Owald et al, 2015). This mechanism would not work for trace conditioning, because (1) at the time the US occurs, CS-induced increase in KCs' calcium concentration is back to baseline levels (Figure 2D, Supplementary Figure 2), and (2) trace conditioning does not involve the rutabaga adenylyl cyclase (Shuai et al, 2011).…”

“…In KCs, the CS-induced increase in intracellular calcium and the US-(dopamine)-induced second messengers synergistically activate an adenylyl cyclase (Duerr and Quinn, 1982; Dudaí et al, 1983; Tomchik and Davis, 2009; Gervasi et al, 2010), which alters the synaptic strength between KCs and MB output neurons (MBONs). This change in KC-to-MBON synapses is thought to encode the associative odor memory (Dubnau et al, 2001; McGuire et al, 2001; Schwaerzel et al, 2003; Séjourné et al, 2011; Pai et al, 2013; Zhang and Roman, 2013; Aso et al, 2014b; Bouzaiane et al, 2015; Cohn et al, 2015; Hige et al, 2015a; Owald et al, 2015). …”

Functional neuroanatomy of Drosophila olfactory memory formation

“…In addition, stimulated conditioning of flies with odor and thermogenetic activation of DAn revealed that neuronal plasticity, revealed through functional imaging using G-CaMP of subsequent calcium responses to odors, occurs primarily in the g MBn (Boto et al 2014). In an independent study, the presynaptic activity of g MBn was shown to be inhibited by G(o) signaling using synapto-pHluorin imaging (Zhang and Roman 2013). Moreover, expression in the g MBn of the rut AC, a coincidence detector, provides partial to complete rescue of memory immediately after conditioning, depending on the g MBn driver used (Zars et al 2000;Akalal et al 2006;Blum et al 2009;Xie et al 2013).…”