Methods for chair restraint and training of the common marmoset on oculomotor tasks.

The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a "gap effect," a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.

[1]  David A. Leopold,et al.  The marmoset monkey as a model for visual neuroscience , 2015, Neuroscience Research.

[2]  K. Mansfield,et al.  Marmoset models commonly used in biomedical research. , 2003, Comparative medicine.

[3]  D. Munoz,et al.  Neuronal Activity in Monkey Superior Colliculus Related to the Initiation of Saccadic Eye Movements , 1997, The Journal of Neuroscience.

[4]  R. Douglas,et al.  A Quantitative Map of the Circuit of Cat Primary Visual Cortex , 2004, The Journal of Neuroscience.

[5]  P. Goldman-Rakic,et al.  Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. , 1989, Journal of neurophysiology.

[6]  H. Komatsu,et al.  Relation of cortical areas MT and MST to pursuit eye movements. III. Interaction with full-field visual stimulation. , 1988, Journal of neurophysiology.

[7]  Dylan F. Cooke,et al.  Improved methods for acrylic-free implants in nonhuman primates for neuroscience research. , 2017, Journal of neurophysiology.

[8]  Cory T. Miller,et al.  Optogenetic manipulation of neural circuits in awake marmosets. , 2016, Journal of neurophysiology.

[9]  D. Bendor,et al.  The neuronal representation of pitch in primate auditory cortex , 2005, Nature.

[10]  B. Fischer,et al.  Human express saccades: extremely short reaction times of goal directed eye movements , 2004, Experimental Brain Research.

[11]  A. C. Roberts,et al.  Perseveration and Strategy in a Novel Spatial Self-Ordered Sequencing Task for Nonhuman Primates: Effects of Excitotoxic Lesions and Dopamine Depletions of the Prefrontal Cortex , 1998, Journal of Cognitive Neuroscience.

[12]  Xiaoqin Wang,et al.  Sustained firing in auditory cortex evoked by preferred stimuli , 2005, Nature.

[13]  K. Fukushima,et al.  Disturbances of voluntary control of saccadic eye movements in schizophrenic patients , 1988, Biological Psychiatry.

[14]  Hellmut Merkle,et al.  Longitudinal functional magnetic resonance imaging in animal models. , 2011, Methods in molecular biology.

[15]  C. Bruce,et al.  Primate frontal eye fields. I. Single neurons discharging before saccades. , 1985, Journal of neurophysiology.

[16]  M. Schlag-Rey,et al.  Evidence for a supplementary eye field. , 1987, Journal of neurophysiology.

[17]  H. Okano,et al.  Generation of transgenic non-human primates with germline transmission , 2009, Nature.

[18]  H. Okano,et al.  Common marmoset as a new model animal for neuroscience research and genome editing technology , 2014, Development, growth & differentiation.

[19]  M M Merzenich,et al.  Representation of a species-specific vocalization in the primary auditory cortex of the common marmoset: temporal and spectral characteristics. , 1995, Journal of neurophysiology.

[20]  Michael S. Osmanski,et al.  Measurement of absolute auditory thresholds in the common marmoset (Callithrix jacchus) , 2011, Hearing Research.

[21]  K T O'Byrne,et al.  A restraint system for the common marmoset (Callithrix jacchus) , 1988, Laboratory animals.

[22]  Erika Sasaki,et al.  Prospects for genetically modified non-human primate models, including the common marmoset , 2015, Neuroscience Research.

[23]  J. Feldon,et al.  Performance of the marmoset monkey on computerized tasks of attention and working memory. , 2004, Brain research. Cognitive brain research.

[24]  R. Dodge,et al.  AN EXPERIMENTAL STUDY OF THE OCULAR REACTIONS OF THE INSANE FROM PHOTOGRAPHIC RECORDS. , 1908 .

[25]  Michael S. Osmanski,et al.  The Role of Harmonic Resolvability in Pitch Perception in a Vocal Nonhuman Primate, the Common Marmoset (Callithrix jacchus) , 2013, The Journal of Neuroscience.

[26]  Hiroshi Kawasaki,et al.  Long-Term Two-Photon Calcium Imaging of Neuronal Populations with Subcellular Resolution in Adult Non-human Primates. , 2015, Cell reports.

[27]  Ziad M Hafed,et al.  Neuronal control of fixation and fixational eye movements , 2017, Philosophical Transactions of the Royal Society B: Biological Sciences.

[28]  T. Preuss Taking the Measure of Diversity: Comparative Alternatives to the Model-Animal Paradigm in Cortical Neuroscience , 2000, Brain, Behavior and Evolution.

[29]  R. Wurtz Visual receptive fields of striate cortex neurons in awake monkeys. , 1969, Journal of neurophysiology.

[30]  David C Lyon,et al.  Distribution across cortical areas of neurons projecting to the superior colliculus in new world monkeys. , 2005, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[31]  Samuel G. Solomon,et al.  A simpler primate brain: the visual system of the marmoset monkey , 2014, Front. Neural Circuits..

[32]  Cory T. Miller,et al.  Motion dependence of smooth pursuit eye movements in the marmoset. , 2015, Journal of neurophysiology.

[33]  John H. Reynolds,et al.  Active Vision in Marmosets: A Model System for Visual Neuroscience , 2014, The Journal of Neuroscience.

[34]  J. Kaas,et al.  Microstimulation and architectonics of frontoparietal cortex in common marmosets (Callithrix jacchus) , 2008, The Journal of comparative neurology.

[35]  D Carden,et al.  Eye movements induced by electrical stimulation of the frontal eye fields of marmosets and squirrel monkeys. , 1982, Brain, behavior and evolution.

[36]  T. Robbins,et al.  Dissociable Forms of Inhibitory Control within Prefrontal Cortex with an Analog of the Wisconsin Card Sort Test: Restriction to Novel Situations and Independence from “On-Line” Processing , 1997, The Journal of Neuroscience.

[37]  A. Fuchs,et al.  Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement. , 1970, Journal of neurophysiology.

[38]  Maureen A. Hagan,et al.  Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion. , 2017, Journal of neurophysiology.

[39]  K. Johnston,et al.  Neurophysiology and neuroanatomy of reflexive and voluntary saccades in non-human primates , 2008, Brain and Cognition.

[40]  T. Paus Location and function of the human frontal eye-field: A selective review , 1996, Neuropsychologia.

[41]  Atsushi Takemoto,et al.  Development of a compact and general-purpose experimental apparatus with a touch-sensitive screen for use in evaluating cognitive functions in common marmosets , 2011, Journal of Neuroscience Methods.

[42]  Michele A. Basso,et al.  The tell-tale tasks: A review of saccadic research in psychiatric patient populations , 2008, Brain and Cognition.

[43]  R. M. Siegel,et al.  Neurons of area 7 activated by both visual stimuli and oculomotor behavior , 2004, Experimental Brain Research.

[44]  R Porter,et al.  A headpiece for recording discharges of neurons in unrestrained monkeys. , 1971, Electroencephalography and clinical neurophysiology.

[45]  J. Hearn,et al.  Restraining device for small monkeys , 1977, Laboratory animals.

[46]  F. A. Miles,et al.  Decreases in the Latency of Smooth Pursuit and Saccadic Eye Movements Produced by the “Gap Paradigm” in the Monkey , 1996, Vision Research.

[47]  Judith M Burkart,et al.  Marmosets as model species in neuroscience and evolutionary anthropology , 2015, Neuroscience Research.

[48]  Y. Yamaguchi,et al.  Brain/MINDS: A Japanese National Brain Project for Marmoset Neuroscience , 2016, Neuron.

[49]  Ravi S. Menon,et al.  Frontoparietal Functional Connectivity in the Common Marmoset , 2016, Cerebral cortex.

[50]  D. Munoz,et al.  A neural correlate for the gap effect on saccadic reaction times in monkey. , 1995, Journal of neurophysiology.

[51]  Daniel Bendor,et al.  Dual-Pitch Processing Mechanisms in Primate Auditory Cortex , 2012, The Journal of Neuroscience.

[52]  Evan D. Remington,et al.  An Operant Conditioning Method for Studying Auditory Behaviors in Marmoset Monkeys , 2012, PloS one.

[53]  P. Mitra,et al.  Brain-mapping projects using the common marmoset , 2015, Neuroscience Research.

[54]  W. D. Halliburton,et al.  Cortical lamination and localisation in the brain of the marmoset , 1910 .

[55]  Samuel U. Nummela,et al.  Psychophysical measurement of marmoset acuity and myopia , 2017, Developmental neurobiology.

[56]  Xiaoqin Wang,et al.  Neural representations of temporally asymmetric stimuli in the auditory cortex of awake primates. , 2001, Journal of neurophysiology.

[57]  D P Munoz,et al.  Saccadic reaction time in the monkey: advanced preparation of oculomotor programs is primarily responsible for express saccade occurrence. , 1996, Journal of neurophysiology.

[58]  Xiaoqin Wang,et al.  Contrast Tuning in Auditory Cortex , 2003, Science.

[59]  Daniel Bendor,et al.  Differential neural coding of acoustic flutter within primate auditory cortex , 2007, Nature Neuroscience.

[60]  A. Roberts,et al.  Inhibitory control and affective processing in the prefrontal cortex: neuropsychological studies in the common marmoset. , 2000, Cerebral cortex.

[61]  C. Klein,et al.  A hundred years of eye movement research in psychiatry , 2008, Brain and Cognition.

[62]  B. Fischer,et al.  Saccadic eye movements after extremely short reaction times in the monkey , 1983, Brain Research.

[63]  Atsushi Iriki,et al.  Sustained performance by common marmosets in a delayed matching to position task with variable stimulus presentations , 2016, Behavioural Brain Research SreeTestContent1.

[64]  R. Wurtz,et al.  Activity of superior colliculus in behaving monkey. 3. Cells discharging before eye movements. , 1972, Journal of neurophysiology.

[65]  Sohee Park,et al.  Schizophrenics show spatial working memory deficits. , 1992, Archives of general psychiatry.

[66]  Stefan Everling,et al.  Focused attention modulates visual responses in the primate prefrontal cortex. , 2004, Journal of neurophysiology.

[67]  M. Saslow Effects of components of displacement-step stimuli upon latency for saccadic eye movement. , 1967, Journal of the Optical Society of America.

[68]  Kathleen J. Burman,et al.  The cortical motor system of the marmoset monkey (Callithrix jacchus) , 2015, Neuroscience Research.