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Striatal cholinergic interneurons Drive GABA release from dopamine terminals
Alexandra B Nelson1, Nora Hammack2, Cindy F Yang3
1The Gladstone Institutes, San Francisco, CA, 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron
|March 12, 2014
Summary
Striatal cholinergic interneurons co-opt dopamine terminals to release GABA, inhibiting output neurons. This action-potential-independent pathway is crucial for motor control and learning.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Neuropharmacology
Background:
- Striatal cholinergic interneurons play key roles in motor control, learning, and plasticity.
- Synchronous activation of these interneurons elicits inhibitory currents in projection neurons, but the underlying mechanism is unclear.
Purpose of the Study:
- To elucidate the mechanism by which striatal cholinergic interneurons mediate inhibitory synaptic currents in dorsal striatal projection neurons.
Main Methods:
- Optogenetics and whole-cell recordings in brain slices.
- Pharmacological manipulation including vesicular monoamine transport inhibitors and 6-hydroxydopamine treatment.
- Ablation of striatal fast-spiking interneurons.
Main Results:
- A significant component of the inhibitory response was action-potential-independent and mediated by nicotinic receptors.
- The GABAergic currents were unaffected by fast-spiking interneuron ablation.
- These currents were significantly reduced by dopamine terminal destruction or vesicular monoamine transport inhibition, indicating dopamine terminals as the source of GABA release.
Conclusions:
- Striatal cholinergic interneurons utilize dopamine terminals to release GABA, providing a rapid inhibitory control mechanism for striatal output neurons.
- This pathway offers novel insights into the interplay between cholinergic and dopaminergic systems in striatal function.
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