Role of tonically-active neurons in the control of striatal function: cellular mechanisms and behavioral correlates

1. The striatum is primarily involved in motor planning and motor learning. Human diseases involving its complex circuitry lead to movement disorders such as Parkinson's disease (PD) and Huntington's disease (HD). Moreover the striatum has been involved in processes linked to reward, cognition and drug addiction. 2. The high content of acetylcholine (ACh) found in the striatum is due to the presence of cholinergic interneurons. The intrinsic electrical and synaptic properties of these interneurons have been recently characterized. However, their functional significance is far from being fully elucidated. 3. In vivo electrophysiological experiments from behaving monkeys have identified these cholinergic interneurons as "Tonically Active Neurons" (TANs). They are activated by presentation of sensory stimuli of behavioral significance or linked to reward. 4. Experimental evidence showed that integrity of the nigrostriatal dopaminergic system is essential for TANs to express learned activity. 5. PD is known to be due to the loss of the nigrostriatal dopaminergic pathway and the ensuing imbalance between the content of dopamine and acetylcholine in the striatum. This evidence supports the hypothesis that cholinergic interneurons, or TANs, play a key role in the modulation of striatal function.