- Mg Block of Drosophila NMDA Receptors Is Required for Long-Term Memory Formation and CREB-Dependent ...
Neuron, Volume 74, Issue 5, 7 June 2012, Pages 887-898
Tomoyuki Miyashita, Yoshiaki Oda, Junjiro Horiuchi, Jerry C.P. Yin, Takako Morimoto and Minoru Saitoe
SummaryNMDA receptor (NMDAR) channels allow Ca2+ influx only during correlated activation of both pre- and postsynaptic cells; a Mg2+ block mechanism suppresses NMDAR activity when the postsynaptic cell is inactive. Although the importance of NMDARs in associative learning and long-term memory (LTM) formation has been demonstrated, the role of Mg2+ block in these processes remains unclear. Using transgenic flies expressing NMDARs defective for Mg2+ block, we found that Mg2+ block mutants are defective for LTM formation but not associative learning. We demonstrate that LTM-dependent increases in expression of synaptic genes, including homer, staufen, and activin, are abolished in flies expressing Mg2+ block defective NMDARs. Furthermore, we show that genetic and pharmacological reduction of Mg2+ block significantly increases expression of a CREB repressor isoform. Our results suggest that Mg2+ block of NMDARs functions to suppress basal expression of a CREB repressor, thus permitting CREB-dependent gene expression upon LTM induction.
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- Short- and Long-Term Memory in Drosophila Require cAMP Signaling in Distinct Neuron Types
Current Biology, Volume 19, Issue 16, 25 August 2009, Pages 1341-1350
Allison L. Blum, Wanhe Li, Mike Cressy and Josh Dubnau
A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view.
Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca2+-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in γ neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons.
Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB γ neurons, and a long-lived trace in α/β neurons.
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- Deconstructing Memory in Drosophila
Current Biology, Volume 15, Issue 17, 6 September 2005, Pages R700-R713
Carla Margulies, Tim Tully and Josh Dubnau
SummaryUnlike most organ systems, which have evolved to maintain homeostasis, the brain has been selected to sense and adapt to environmental stimuli by constantly altering interactions in a gene network that functions within a larger neural network. This unique feature of the central nervous system provides a remarkable plasticity of behavior, but also makes experimental investigations challenging. Each experimental intervention ramifies through both gene and neural networks, resulting in unpredicted and sometimes confusing phenotypic adaptations. Experimental dissection of mechanisms underlying behavioral plasticity ultimately must accomplish an integration across many levels of biological organization, including genetic pathways acting within individual neurons, neural network interactions which feed back to gene function, and phenotypic observations at the behavioral level. This dissection will be more easily accomplished for model systems such as Drosophila, which, compared with mammals, have relatively simple and manipulable nervous systems and genomes. The evolutionary conservation of behavioral phenotype and the underlying gene function ensures that much of what we learn in such model systems will be relevant to human cognition. In this essay, we have not attempted to review the entire Drosophila memory field. Instead, we have tried to discuss particular findings that provide some level of intellectual synthesis across three levels of biological organization: behavior, neural circuitry and biochemical pathways. We have attempted to use this integrative approach to evaluate distinct mechanistic hypotheses, and to propose critical experiments that will advance this field.