Acetylcholine (ACh) is a transmitter essential for striatal function, and changes in striatal cholinergic drive have been implicated in the pathophysiology of movement disorders such as Parkinson's disease. The source of ACh in the striatum is large aspiny (LA) cholinergic interneurons, whose primary innervation stems from cortical and thalamic glutamatergic afferents. Ion channels targeted downstream of metabotropic glutamate receptors (mGluRs) in these cells contribute to regulation of their membrane potential and excitability, and thus to their release of ACh. TASK-3 is a member of the KCNK family of leak potassium channels known to be modulated downstream of G-protein coupled receptors, and shown by in situ hybridization to be expressed in neurons suspected to be cholinergic interneurons. In this research proposal, I use immunohistochemistry and whole cell electrophysiology to establish expression of TASK-3 channels in large aspiny cholinergic interneurons (Specific Aim 1) and show their modulation as targets downstream of mGluRs (Specific Aim 2). Finally, I confirm my findings using a mouse model in which TASK-3 is conditionally deleted (Specific Aim 3).
| Berg, Allison P; Bayliss, Douglas A (2007) Striatal cholinergic interneurons express a receptor-insensitive homomeric TASK-3-like background K+ current. J Neurophysiol 97:1546-52 |
| Berg, Allison P; Sen, Neil; Bayliss, Douglas A (2007) TrpC3/C7 and Slo2.1 are molecular targets for metabotropic glutamate receptor signaling in rat striatal cholinergic interneurons. J Neurosci 27:8845-56 |
| Torborg, Christine L; Berg, Allison P; Jeffries, Brian W et al. (2006) TASK-like conductances are present within hippocampal CA1 stratum oriens interneuron subpopulations. J Neurosci 26:7362-7 |
