ABSTRACT
BACKGROUND: 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. RESULTS: 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 Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma 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. CONCLUSIONS: Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.
Subject(s)
Adenylyl Cyclases/physiology , Cyclic AMP/physiology , Drosophila Proteins/physiology , Drosophila melanogaster/physiology , Memory/physiology , Mushroom Bodies/physiology , Neurons/physiology , Second Messenger Systems/physiology , Adenylyl Cyclases/deficiency , Adenylyl Cyclases/genetics , Animals , Animals, Genetically Modified , Avoidance Learning/physiology , Conditioning, Classical/physiology , Drosophila Proteins/deficiency , Drosophila Proteins/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Female , Gene Knockout Techniques , Genetic Complementation Test , Male , Memory, Short-Term/physiology , Mushroom Bodies/cytology , Neurons/classification , Point Mutation , Recombinant Fusion Proteins/physiology , Retention, Psychology/physiology , Smell/physiologyABSTRACT
4-Aryl-substituted N-thiolated beta-lactams are a new family of antibacterial agents possessing unique structure-activity profiles and a mode of action. Unlike traditional beta-lactam antibiotics, which require highly polar enzyme-binding groups, these lactams bear hydrophobic groups on their side chains. In this study, we examine the effect that increasing hydrophobicity, through fluorine substitution in the C(4) aryl ring, has on the antibacterial properties.