Genome-wide transcriptional changes associated with enhanced activity in the Drosophila nervous system.
Neuronal plasticity is an important feature of the developing brain and requires neuronal circuits to reconfigure their functional connectivity depending upon activity patterns. To explore changes in neuronal function that occur downstream of altered activity, we performed an expression analysis in Drosophila mutants with acute or chronic alterations in neuronal activity. We find that seizure induction leads to an overproliferation of synaptic connections, indicating that activity-dependent neuronal rewiring occurs in Drosophila. To analyze transcriptional recoding during altered neuronal activity, we performed genome-wide DNA microarray analysis following multiple seizure induction and recovery paradigms. Approximately 250 genes implicated in cell adhesion, membrane excitability, and cellular signaling are differentially regulated, including the Kek 2 neuronal cell adhesion protein, which, as we demonstrate, functions as a regulator of synaptic growth. These data identify a collection of activity-regulated transcripts that may link changes in neuronal firing patterns to transcription-dependent modulation of brain function, including activity-dependent synaptic rewiring.
Guan
Zhuo
Z
The Picower Institute for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Saraswati
Sudipta
S
Adolfsen
Bill
B
Littleton
J Troy
JT
D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D015153:Blotting, Western / Q000379:methods; D004330:Drosophila / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D016678:Genome; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods; D008959:Models, Neurological; D009132:Muscles / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic
D029721:Drosophila Proteins; C105054:Kek2 protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger