Smooth pursuit eye movements in primates provide an accessible example of motor behavior guided by sensory inputs. Pursuit movements are controlled by cortical representations of target motion and access some of the same higher cortical regions implicated in planning and decision making. In preliminary work we have shown that pursuit behavior is variable but surprisingly precise, that the variability has a simple structure, and that it can be attributed mainly to errors in sensory estimates of target motion parameters. The surprisingly precise relationship between eye trajectories and target motion is established over time windows of 100 ms durations. Thus, pursuit gives us a remarkable situation - a genuine primate sensory-motor behavior in which the input-output relationship is computational simple, while relevant time scales are short enough that each cell can contribute at most a few spikes. Thus, in the equation in which behavior is a function of neural activity, both sides are much simpler than might have been expected. The potentially combinatorial complexity involved in a complete analysis of the neural code itself and the connection between spike trains and behavior is dramatically simplified. We propose 1) to understand the neural codes for sensory and motor signals at multiple levels of the neural circuit for pursuit, 2) to correlate the activity of single cortical, brainstem and cerebellar neurons with the trial-to-trial variability of motor output in awake, behaving animals, and 3) to bridge the gap from what we can measure (co-variation of neural and behavioral responses in single trials) to what we want to know (architecture and signal processing in the full sensory-motor circuit). The outcome of this line of research will be an understanding of how multiple cortical and sub-cortical areas work together to generate a single kind of voluntary movement. It will have direct impact on how we understand neurological disorders of movement, and on the consequences of disruptions or enhancements of correlations between neurons. Correlations and neuronal oscillations are an important feature of normal motor function, and this project will help us to understand how to understand their malfunctions and to design behavioral therapies to mitigate their disruption in epilepsy, nystagmus, and movement disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017210-02
Application #
7120034
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Hunter, Chyren
Project Start
2005-09-15
Project End
2010-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$297,565
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lisberger, Stephen G; Medina, Javier F (2015) How and why neural and motor variation are related. Curr Opin Neurobiol 33:110-6
Joshua, M; Lisberger, S G (2015) A tale of two species: Neural integration in zebrafish and monkeys. Neuroscience 296:80-91
Ravits, John (2014) Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 262 Pt B:121-6
Joshua, Mati; Medina, Javier F; Lisberger, Stephen G (2013) Diversity of neural responses in the brainstem during smooth pursuit eye movements constrains the circuit mechanisms of neural integration. J Neurosci 33:6633-47
Stephens, Greg J; Bueno de Mesquita, Matthew; Ryu, William S et al. (2011) Emergence of long timescales and stereotyped behaviors in Caenorhabditis elegans. Proc Natl Acad Sci U S A 108:7286-9
Chaisanguanthum, Kris S; Lisberger, Stephen G (2011) A neurally efficient implementation of sensory population decoding. J Neurosci 31:4868-77
Lisberger, Stephen G (2010) Visual guidance of smooth-pursuit eye movements: sensation, action, and what happens in between. Neuron 66:477-91
Stephens, Greg J; Johnson-Kerner, Bethany; Bialek, William et al. (2010) From modes to movement in the behavior of Caenorhabditis elegans. PLoS One 5:e13914
Medina, Javier F; Lisberger, Stephen G (2009) Encoding and decoding of learned smooth-pursuit eye movements in the floccular complex of the monkey cerebellum. J Neurophysiol 102:2039-54
Osborne, Leslie C; Palmer, Stephanie E; Lisberger, Stephen G et al. (2008) The neural basis for combinatorial coding in a cortical population response. J Neurosci 28:13522-31

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