Bridging behavior and physiology: Ion‐channel perspective on mushroom body‐dependent olfactory learning and memory in Drosophila

Abstract

An important body of evidence documents the differential expression of ion channels in brains, suggesting they are essential to endow particular brain structures with specific physiological properties. Because of their role in correlating inputs and outputs in neurons, modulation of voltage-dependent ion channels (VDICs) can profoundly change neuronal network dynamics and performance, and may represent a fundamental mechanism for behavioral plasticity, one that has received less attention in learning and memory studies. Revisiting three paradigmatic mutations altering olfactory learning and memory in Drosophila (dunce, leonardo, amnesiac) a link was established between each mutation and the operation of VDICs in Kenyon cells, the intrinsic neurons of the mushroom bodies (MBs). In Drosophila, MBs are essential to the emergence of olfactory associative learning and retention. Abnormal ion channel operation might underlie failures in neuronal physiology, and be crucial to understand the abnormal associative learning and retention phenotypes the mutants display. We also discuss the only case in which a mutation in an ion channel gene (shaker) has been directly linked to olfactory learning deficits. We analyze such evidence in light of recent discoveries indicating an unusual ion current profile in shaker mutant MB intrinsic neurons. We anticipate that further studies of acquisition and retention mutants will further confirm a link between such mutations and malfunction of specific ion channel mechanisms in brain structures implicated in learning and memory.

KCNQ Channels Regulate Age-Related Memory Impairment

“…This resulted in a decrease in the afterhyperpolarization (after a train of action potentials, the increase in Ca 2+ activates K + channels leading to a pronounced hyperpolarization) and caused deficits in associative memory. Kv channels have also been implicated in plasticity underlying fly memory [32]–[35] consistent with the conspicuous expression of Kv currents in mushroom body neurons [34], [36], [37]. We have extended these studies by showing dKCNQ has a role in immediate memory, STM and LTM without peripheral defects.…”

A toolbox for light control of Drosophila behaviors through Channelrhodopsin 2‐mediated photoactivation of targeted neurons

“…We further explored whether light stimulation of ChR2 can be used to activate neurons in a higher-order center of the fly brain ) the mushroom bodies, which play an important role in associative olfactory learning and memory (de Belle, 1995;Carlson, 2001;Heisenberg, 2003;Gasque et al, 2006). The Drosophila mushroom bodies contain about 5000 principal neurons ) the KCs, which give rise to axons that provide local circuits between afferents and efferents, and thus serve integrative functions.…”

Ion channels to inactivate neurons in Drosophila

“…Electrical inactivation of postsynaptic cells using DORK caused an increase in synaptic phosphorylation of T306 and concomitant reduction in T287, these changes were regulated by the PDZ-scaffolding molecule, CASK (Lu et al, 2003; Hodge et al, 2006). Activated CaMKII is known to directly bind or modulate a number of K + channels and glutamate receptors regulating neuronal excitability in a range of systems (Griffith et al, 1994; Park et al, 2001; Yao and Wu, 2001; Haghighi et al, 2003; Sun et al, 2004; Nelson et al, 2005; Gasque et al, 2006), while CASK also interacts and changes the activity of a number of synaptic ion channels and receptors (Hsueh, 2006). …”

“…Drosophila has a similar range of interacting intrinsic and synaptic plasticity mechanisms, some pre- and some post-synaptic. These have mostly been studied at glutamatergic or cholinergic synapses with conserved roles for CaMKII, PKA, CREB, potassium (K + ) channels and NMDA receptors in mechanisms of plasticity and learning between Drosophila and humans (Littleton and Ganetzky, 2000; Giese et al, 2001; Haghighi et al, 2003; Rohrbough et al, 2003; Gasque et al, 2006; Wu et al, 2007; Schmid et al, 2008; Turrigiano, 2008). …”