title: Effects of Optogenetic Activation of Corticothalamic Terminals in the Motor Thalamus of Awake Monkeys.
abstract: The role of the corticothalamic projection in the ventral motor thalamus remains poorly understood. Therefore, we studied the electrophysiological responses of neurons in the basal ganglia and cerebellar receiving-territories of the motor thalamus (BGMT and CbMT, respectively) using optogenetic activation of corticothalamic projections in awake rhesus macaques. After injections of viral vectors carrying the excitatory opsins ChR2 or C1V1 into the primary motor and premotor cortices of two monkeys, we used optrodes to light activate opsin-expressing neurons in cortex or their terminals in the thalamus while simultaneously recording the extracellular activity of neurons in the vicinity of the stimulation sites. As expected, light activation of opsins in the cerebral cortex evoked robust, short-latency increases in firing of cortical neurons. In contrast, light stimulation of corticothalamic terminals induced small-amplitude, long-latency increases and/or decreases of activity in thalamic neurons. In postmortem material, opsins were found to be expressed in cell bodies and dendrites of cortical neurons and along their corticothalamic projections. At the electron microscopic level, opsin labeling was confined to unmyelinated preterminal axons and small terminals that formed asymmetric synapses with dendrites of projection neurons or GABAergic interneurons in BGMT and CbMT and with neurons in the reticular thalamic nucleus. The morphological features of the transfected terminals, along with the long latency and complex physiological responses of thalamic neurons to their activation, suggest a modulatory role of corticothalamic afferents upon the primate ventral motor thalamus.
  
  
  CONCLUSIONS
  This study provides the first analysis of the physiological effects of cortical inputs on the activity of neurons in the primate ventral motor thalamus using light activation of opsin-containing corticothalamic terminals in awake monkeys. We found that selective light activation of corticothalamic terminals in contact with distal dendrites of thalamocortical neurons and GABAergic interneurons elicits complex patterns of slowly developing excitatory and inhibitory effects in thalamic neurons of the basal ganglia- and cerebellar-receiving regions of the motor thalamus. Our observations suggest a modulatory (instead of a "driver") role of the corticothalamic system in the primate ventral motor thalamus.
authors.affiliation: Yerkes National Primate Research Center and School of Medicine, Department of Neurology, Emory University, Atlanta, Georgia 30329 agalvan@emory.edu.
authors.forename: Adriana
authors.identifier: http://orcid.org/0000-0001-9939-0130
authors.initials: A
authors.lastname: Galvan
authors.affiliation: Yerkes National Primate Research Center and.
authors.forename: Xing
authors.initials: X
authors.lastname: Hu
authors.affiliation: Yerkes National Primate Research Center and School of Medicine, Department of Neurology, Emory University, Atlanta, Georgia 30329.
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
authors.affiliation: Yerkes National Primate Research Center and School of Medicine, Department of Neurology, Emory University, Atlanta, Georgia 30329.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichmann
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D062308:Optogenetics / Q000379:methods*; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000502:physiology*; D014851:Wakefulness
keywords: C1V1; ChR2; motor cortex; motor thalamus; optogenetics; single unit recording