Parkinsonism is attributed to an imbalance in the dopaminergic-cholinergic tone to the striatum. The primary source of acetylcholine to the striatum is the tonically active cholinergic interneurons. Converging lines of evidence suggest that these neurons form a synchronized network that modulates striatal output and learning. The goal of this study is to reveal the underlying mechanisms of synchrony in this network. Preliminary evidence suggests that these neurons synchronize when bursting, and that their bursting depends on calcium-dependent potassium currents. Voltage and current clamp recording techniques in conjunction with pharmacological treatments will be used in rat striatal slices to identify the calcium channels that are coupled to these potassium currents. Calcium imaging will be used to study the distribution of these channels at the soma and proximal dendrites. Spontaneous and evoked cholinergic synaptic currents will be characterized in slices of bursting neurons. Dual recordings will be used to search for chemical and electrical synapses and to study short-term synaptic plasticity. Phase response functions and synaptic currents will be measured and used to predict network synchrony according to the theory of weakly coupled oscillators.
| Goldberg, Joshua A; Teagarden, Mark A; Foehring, Robert C et al. (2009) Nonequilibrium calcium dynamics regulate the autonomous firing pattern of rat striatal cholinergic interneurons. J Neurosci 29:8396-407 |
| Goldberg, Joshua A; Deister, Chris A; Wilson, Charles J (2007) Response properties and synchronization of rhythmically firing dendritic neurons. J Neurophysiol 97:208-19 |
| Ding, Jun; Guzman, Jaime N; Tkatch, Tatiana et al. (2006) RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. Nat Neurosci 9:832-42 |
| Wilson, Charles J; Goldberg, Joshua A (2006) Origin of the slow afterhyperpolarization and slow rhythmic bursting in striatal cholinergic interneurons. J Neurophysiol 95:196-204 |
| Goldberg, Joshua A; Wilson, Charles J (2005) Control of spontaneous firing patterns by the selective coupling of calcium currents to calcium-activated potassium currents in striatal cholinergic interneurons. J Neurosci 25:10230-8 |
