Tachykinins increase [3H]acetylcholine release in mouse striatum through multiple receptor subtypes

Area of Science:

• Neuroscience
• Neuropharmacology
• Striatal circuitry

Background:

• Tachykinins are implicated in mammalian striatal function, particularly in regulating acetylcholine release.
• Cholinergic interneurons in the striatum are key targets for neuromodulation.

Purpose of the Study:

• To investigate the role of tachykinins and their receptors in modulating mouse striatal cholinergic interneurons.
• To elucidate the specific tachykinin receptor subtypes involved in acetylcholine release.

Main Methods:

• Whole-cell patch-clamp recordings in mouse striatal slices to assess neuronal activity.
• Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) to confirm neuron identity and receptor expression.
• In vitro superfusion techniques to measure acetylcholine release, modulated by specific agonists and antagonists.

Main Results:

• Selective agonists for neurokinin-1, neurokinin-2, and neurokinin-3 receptors induced dose-dependent depolarization of cholinergic interneurons.
• [Sar9,Met(O2)11]substance P, [beta-ala8]neurokinin A(4-10), and senktide dose-dependently increased acetylcholine release.
• Phospholipase C and protein kinase C inhibitors differentially affected agonist-induced acetylcholine release, highlighting distinct signaling pathways. Neurokinin-2 receptor agonists showed a unique effect in mice.

Conclusions:

• Tachykinins significantly modulate the activity of mouse striatal cholinergic interneurons.
• Neurokinin-2 receptors play a previously unrecognized role in mouse striatal function, particularly in regulating acetylcholine release.