Signaling at A-Kinase Anchoring Proteins Organizes Anesthesia-Sensitive Memory inDrosophila

Abstract

The ubiquitous cAMP-protein kinase A (PKA) signaling pathway exhibits complex temporal requirements during the time course of associative memory processing. This directly raises questions about the molecular mechanisms that provide signaling specificity to this pathway. Here, we use Drosophila olfactory conditioning to show that divergent cAMP signaling is mediated by functionally distinct pools of PKA. One particular pool is organized via the PKA regulatory type II subunit at the level of A-kinase anchoring proteins (AKAPs), a family of scaffolding proteins that provides focal points of spatiotemporal signal integration. This AKAP-bound pool of PKA is acting within neurons of the mushroom bodies to support a late phase of aversive memory. The requirement for AKAP-bound PKA signaling is limited to aversive memory, but dispensable during appetitive memory. This finding suggests the existence of additional mechanisms to support divergence within the cAMP-PKA signaling pathway during memory processing. Together, our results show that subcellular organization of signaling components plays a key role in memory processing.

Rapid Consolidation to aradishand Protein Synthesis-Dependent Long-Term Memory after Single-Session Appetitive Olfactory Conditioning inDrosophila

“…The requirement for spaced training has been suggested to reflect the presence of a mechanistic threshold for LTM induction (Yin et al, 1994;Isabel et al, 2004) because a single training session, or even 10 training sessions, with no rest (massed training) does not form LTM . Two reports of appetitive conditioning in Drosophila using a two-trial massed procedure observed measurable levels of memory up to 24 h after training (Tempel et al, 1983;Schwaerzel et al, 2007), and we previously determined that flies trained with a 2 min odor exposure paired with sucrose revealed robust memory performance up to 6 h (Keene et al, 2006;Krashes et al, 2007). We therefore further investigated the perdurance of appetitive memory following our previously described single conditioning session protocol.…”

“…disrupted after a 1 min cold-shock anesthesia administered 30 min before testing (Schwaerzel et al, 2007).…”

“…Flies can also be trained with odor and a more ethologically relevant sucrose reward (Tempel et al, 1983;Schwaerzel et al, 2003Schwaerzel et al, , 2007Keene et al, 2006;Kim et al, 2007), and even in the first report, it was noted that memory after two trials of appetitive conditioning persisted longer than that after two trials of aversive conditioning (Tempel et al, 1983). We therefore sought to determine whether appetitive olfactory conditioning could form LTM and whether appetitive LTM formation shared rules and mechanisms with that of aversive LTM.…”

Distinctive Neuronal Networks and Biochemical Pathways for Appetitive and Aversive Memory inDrosophilaLarvae

“…Kenyon cells express G-protein-coupled receptors for the monoamines that represent the US reinforcing property; both OA and DA receptors are preferentially expressed in MB neurons (Han et al, 1996(Han et al, , 1998. Whereas little is known about the intracellular biochemical events triggered by the activation of these receptors, different G-protein-coupled receptors for the monoamines might trigger distinctive molecular components, such as A-kinase anchoring proteins (Lu et al, 2007;Schwaerzel et al, 2007), that may differentiate the efficacy in inducing longer-lived memory within an overlapping set of neurons.…”

Bruchpilot, A Synaptic Active Zone Protein for Anesthesia-Resistant Memory

“…Also at the molecular level, ARM and ASM can be distinguished. For instance, ASM is specifically affected in mutants with the impaired cAMP/protein kinase A (PKA) signaling pathway (e.g., rutabaga, encoding the type I adenylyl cyclase) (Dudai et al, 1988;Folkers et al, 1993;Isabel et al, 2004;Schwaerzel et al, 2007;Shuai et al, 2010). Similarly, Synapsin, a presynaptic vesicle protein essential for the regulation of the reserve pool vesicles, is preferentially required for ASM (Knapek et al, 2010).…”