Anterior portions of the ventral thalamus are the point at which basal ganglia output from the internal globus pallidus (GPi) interacts with thalamic neurons that project to the cerebral cortex. Clinical interventions such as pallidotomy or continuous high frequency stimulation (cHFS) in GPi or the subthalamic nucleus (STN) are designed to reduce inhibitory pallidal input to these thalamic neurons and normalize their activity. It is important to determine how thalamic activity is changed by such interventions.
Specific Aims 1 and 2 of the proposed studies will determine the action of HFS in GPi on pallidal-receiving (PR) thalamic neurons in normal animals and in the MPTP-induced model of Parkinsonism. Neural activity recorded at rest and during reaching movements to targets presented randomly or in a serial reaction time task will be related to the timing and kinematics of the arm movements.
Specific Aims 3 and 4 will use similar tasks to determine the effects of HFS in STN, the major source of excitatory input to GPi. Whereas the basal ganglia provide the major inhibitory input to the PR thalamus, the major source of excitatory input comes from corticothalamic (CT) axons that originate in areas of the cerebral cortex with which the PR thalamus is reciprocally connected. Nothing is known about the signals carried by these CT axons.
In Specific Aim 5, the signals carried by corticothalamic neurons will be compared to those carried by corticobulbar/spinal cells. This will help to determine whether the corticothalamic information provides a tonic input that primarily determines the state of thalamic cells and/or whether it carries task-specific phasic information in a corticothalamic loop that is modulated by pallidal inhibitory output axons. Together, the proposed studies will provide a direct test of the assumed mechanism by which surgically-based interventions for the symptoms of Parkinson's disease act and they will determine corticothalamic activity against which pallidal inhibition is balanced at the thalamus.
| Liu, Ying; Postupna, Nadia; Falkenberg, Jon et al. (2008) High frequency deep brain stimulation: what are the therapeutic mechanisms? Neurosci Biobehav Rev 32:343-51 |
| Anderson, Marjorie E; Postupna, Nadia; Ruffo, Mark (2003) Effects of high-frequency stimulation in the internal globus pallidus on the activity of thalamic neurons in the awake monkey. J Neurophysiol 89:1150-60 |
