The purpose of this project is to elucidate the function and significance of the robust electrical rhythmicity of the neurons in the inferior olive and their relation to the temporal and spatial organization of skilled movement. In this experiments, the Principal Investigator will employ multiple-microelectrode recordings of Purkinje cell complex spike activity in vivo while rats perform skilled movements with their oro-facial and limb muscles. The central working hypothesis of this project is that the muscle synergies required for coordinated movement of multiple limbs depend upon the rhythmic activity of the highly parallel projection from the inferior to the cerebellum. This activity physically and rhythmically modulates motor systems. Indeed, that damage to the inferior in humans animals permanently destroys the temporal and spatial structure of skilled movement is firmly established. Using highly controlled experimental conditions with rats, the Investigator will address the following questions: Does the olivocerebellar system organize a forepaw-tongue movement synergy? If so, how? Does the olivocerebellar system temporally organize a spatially-guided movement produced by bilateral musculature? If so, how? What relationship do the two major afferent systems of the cerebellum, the climbing and the mossy fibers, have in organizing movement? Does uncontrolled rhythmic activity within the inferior olive drive pathologically rhythmic movements, such as those seen during a myoclonic seizure?
| Turecek, Josef; Han, Victor Z; Cuzon Carlson, Verginia C et al. (2016) Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque. J Neurosci 36:6497-502 |
| Turecek, Josef; Yuen, Genevieve S; Han, Victor Z et al. (2014) NMDA receptor activation strengthens weak electrical coupling in mammalian brain. Neuron 81:1375-1388 |
| Oristaglio, J; Hyman West, S; Ghaffari, M et al. (2013) Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning. Neuroscience 248:708-18 |
| Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul et al. (2012) Consensus paper: pathological role of the cerebellum in autism. Cerebellum 11:777-807 |
| Vianney-Rodrigues, Paulo; Iancu, Ovidiu D; Welsh, John P (2011) Gamma oscillations in the auditory cortex of awake rats. Eur J Neurosci 33:119-29 |
| Welsh, John P; Han, Victor Z; Rossi, David J et al. (2011) Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence. Proc Natl Acad Sci U S A 108:10314-9 |
| Placantonakis, Dimitris G; Bukovsky, Anatoly A; Aicher, Sue A et al. (2006) Continuous electrical oscillations emerge from a coupled network: a study of the inferior olive using lentiviral knockdown of connexin36. J Neurosci 26:5008-16 |
| Welsh, John P; Yamaguchi, Hidetoshi; Zeng, Xiao-Hui et al. (2005) Normal motor learning during pharmacological prevention of Purkinje cell long-term depression. Proc Natl Acad Sci U S A 102:17166-71 |
| Welsh, John P; Ahn, Edward S; Placantonakis, Dimitris G (2005) Is autism due to brain desynchronization? Int J Dev Neurosci 23:253-63 |
| Placantonakis, Dimitris G; Bukovsky, Anatoly A; Zeng, Xiao-Hui et al. (2004) Fundamental role of inferior olive connexin 36 in muscle coherence during tremor. Proc Natl Acad Sci U S A 101:7164-9 |
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