Welcome to the Littleton Lab!

We seek to elucidate the molecular and cellular mechanisms underlying neuronal communication. We investigate the molecular machines that drive synapse formation, function and plasticity by combining genetic toolkits with electrophysiology and live imaging of neuronal activity. We leverage the power and versatility of the fruitfly Drosophila melanogaster to study glutamatergic synapses at the level of single active zones in identifiable neuronal populations.

Click the video for a quick tour of our lab and to learn more about our research. You can read more in depth about our research here

Research Questions

Synaptic Transmission

We have developed a genetically-encoded fluorescent reporter that allows us to see individual synaptic vesicles fusing at synapses
  • How does vesicular trafficking control synaptic transmission and neuronal communication? How does calcium influx during an action potential initiate and regulate synaptic communication.
  • How do plasticity mechanisms interface with the core molecular machinery for synaptic vesicle trafficking and fusion to alter neuronal communication?
  • How does the active zone proteome contribute to and differentially regulate spontaneous and evoked synaptic vesicle fusion?
  • How can individual active zones formed by the same neuron show differences in output strength that vary over a 50-fold range?

Synapse Formation

  • How do release sites form between neurons and their partners? What molecular and cellular processes regulate active zone number, active zone protein content and active zone release mode?
  • How does cell-wide availability of key proteins to growing active zones over the entire neuron interface with capture and retention mechanisms for new material at individual active zones?
  • What mechanisms regulate calcium channel trafficking and abundance at single release sites?
  • How do these mechanisms differ across distinct neuronal subpopulations with unique synaptic structure, output strength and plasticity?

Disease-relevant research

Glial-neuronal signaling in Epilepsy and Neuronal Excitability

Neurological Disorders

Autism Spectrum Disorder

Lab Life

Between reading papers and performing experiments, lab members enjoy an active social scene in the lab and across MIT. See more here.