MRC National Institute for Medical Research, London
Science for Health
Caged GABA helps to reveal preminis
27 May 2010
In recent years the simple picture of synaptic transmission, as a one-directional flow of information from presynaptic terminal to postsynaptic dendrite, has changed. A complex set of signalling interactions that modulate ongoing synaptic transmission are now recognised. What has remained unclear is whether synaptic communication is sophisticated enough to generate rapid signals right back to the presynaptic cell.
Miniature synaptic currents (called "minis") recorded in the postsynaptic neuron arise from spontaneous release of vesicular 'packets' of neurotransmitter from the presynaptic neuron in the absence of an action potential. They are often used to measure neural connectivity but their nature and function are not well understood. It is thought that they are involved in the development and maintenance of neuronal circuits. Minis have been shown to play important roles including the regulation of postsynaptic firing, of dendritic protein synthesis and dendritic growth, and of synapse homeostasis.
In a recent report, David Ogden, now working in Paris but previously in NIMR's Division of Neurophysiology, George Papageorgiou and John Corrie of the Division of Physical Biochemistry describe a new class of miniature currents ("preminis") that originate from and are subsequently detected by the presynaptic terminals of GABAergic neurons. Preminis are much smaller in amplitude than conventional minis and in neonatal rats are present for the first 15 days or so after birth. The presence of this presynaptic feedback loop suggests that they control the transmitter release probability in growing GABAergic neurons and may play a critical role in guiding the formation of interneuron networks by enhancing neurotransmitter release at recently formed synapses.
To help establish the axonal location of preminis, the research used a reagent (DPNI-GABA) developed at NIMR by George Papageorgiou and John Corrie to mimic GABAergic transmission by releasing GABA on axon terminals with laser flash photolysis. DPNI-GABA and its widely-used excitatory neurotransmitter counterpart MNI-glutamate originate in programmes to develop 'Caged' neurotransmitters in the Divisions of Physical Biochemistry and Neurophysiology.
The research used localised flash photolytic release of GABA from a reagent (DPNI-GABA) developed in NIMR's Division of Physical Biochemistry by George Papageorgiou and John Corrie. This helped to establish the axonal location of transmitter release.
DPNI-GABA has important advantages over previous reagents for photolytic GABA release, particularly in having very limited effects on GABA receptors prior to photolysis.
John Corrie
Caged GABA
This reagent was first described in:
DPNI-GABA, a tool for investigating the properties and distribution of GABA receptors and for silencing neurons in situ. (2009)
Trigo, FF, Papageorgiou, G, Corrie, JET, and Ogden, D.
Journal of Neuroscience Methods 181: 159-169.
Original article
The research findings are published in full in:
Federico F. Trigo, Brice Bouhours, Philippe Rostaing, George Papageorgiou, John E.T. Corrie, Antoine Triller, David Ogden and Alain Marty. (2010)
Presynaptic miniature Gabaergic currents in developing interneurons.
Neuron, 66(2): 235-247. Publisher abstract
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