Emptage Group | Synaptic Pharmacology

(01865) 271599
nigel.emptage@pharm.ox.ac.uk

We are interested in synaptic transmission. We wish to understand the way in which synapses behave when functioning normally but also how they change during memory formation or when struck by diseases such as Schizophrenia or Alzheimer’s.

A hippocampal pyramidal neurone expressing eGFP, imaged using two-photon microscopy.

The questions we ask are made possible by our experimental approach the central tenet of which is that we visualise functioning synapses in living tissue both in vitro and in vivo. In some instances we structurally monitor the synapse and in others we use optical reporters to reveal activity, such as the release or consequence of neurotransmitter release. This approach has proven to be key in generating a number of well cited publications including characterization of intracellular Ca²⁺stores in pre- (Emptage 2001 Neuron) and post- synaptic compartments (Emptage 1999 Neuron), the first demonstration of optical quantal analysis following LTP (Emptage 2003 Neuron), visualization of silent synapse unmasking (Emptage 2006 Neuron), and a description of presynaptic NMDA receptors in the hippocampus (McGuinness 2010 Neuron). Most recently we have reported how activity-dependent fusion of lysosomes with the neuronal membrane is critical for maintaining synaptic structure, a result with far reaching ramifications.

The execution of imaging able to achieve single-synapse resolution requires specialist instrumentation, some of which we develop ‘in house’. The group’s imaging facilities include confocal and two-photon microscopes, microfiber deep-brain imaging technology (a project conducted in collaboration with Tomas Cizmar’s group, Dundee), total internal reflection microscopy (a collaboration with Cairn Instruments Ltd.) and light-sheet microscopy (a collaboration with the Kishan Dholakia’s group, St Andrews and M-Squared Biophtonics group).