Reinforcing operandum: rapid and reliable learning of skilled forelimb movements by head-fixed rodents.

Stereotaxic head fixation plays a necessary role in current physiological techniques, such as in vivo whole cell recording and two-photon laser-scanning microscopy, that are designed to elucidate the cortical involvement in animal behaviors. In rodents, however, head fixation often inhibits learning and performance of behavioral tasks. In particular, it has been considered inappropriate for head-fixed rodents to be operantly conditioned to perform skilled movements with their forelimb (e.g., lever-press task), despite the potential applicability of the task. Here we have solved this problem conceptually by integrating a lever (operandum) and a rewarding spout (reinforcer) into one ″spout-lever″ device for efficient operant learning. With this device, head-fixed rats reliably learned to perform a pull manipulation of the spout-lever with their right forelimb in response to an auditory cue signal (external-trigger trial, namely, Go trial) within several days. We also demonstrated stable whole cell recordings from motor cortex neurons while the rats were performing forelimb movements in external-trigger trials. We observed a behavior-related increase in the number of action potentials in membrane potential. In the next session, the rats, which had already learned the external-trigger trial, effortlessly performed similar spout-lever manipulation with no cue presentation (internal-trigger trial) additionally. Likewise, some of the rats learned to keep holding the spout-lever in response to another cue signal (No-go trial) in the following session, so that they mastered the Go/No-go discrimination task in one extra day. Our results verified the usefulness of spout-lever manipulation for behavioral experiments employing cutting-edge physiological techniques.

[1]  A P Georgopoulos,et al.  On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  Tomoki Fukai,et al.  Microcircuitry coordination of cortical motor information in self-initiation of voluntary movements , 2009, Nature Neuroscience.

[3]  Karel Svoboda,et al.  Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice , 2010, Nature.

[4]  Celine Mateo,et al.  Motor Control by Sensory Cortex , 2010, Science.

[5]  Yoshikazu Isomura,et al.  Neural Coding of “Attention for Action” and “Response Selection” in Primate Anterior Cingulate Cortex , 2003, The Journal of Neuroscience.

[6]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[7]  J. Kalaska,et al.  Deciding not to GO: neuronal correlates of response selection in a GO/NOGO task in primate premotor and parietal cortex. , 1995, Cerebral cortex.

[8]  Nathan G. Clack,et al.  Vibrissa-Based Object Localization in Head-Fixed Mice , 2010, The Journal of Neuroscience.

[9]  D. Tank,et al.  Intracellular dynamics of hippocampal place cells during virtual navigation , 2009, Nature.

[10]  E. Evarts,et al.  Relation of pyramidal tract activity to force exerted during voluntary movement. , 1968, Journal of neurophysiology.

[11]  Maik C. Stüttgen,et al.  Integration of Vibrotactile Signals for Whisker-Related Perception in Rats Is Governed by Short Time Constants: Comparison of Neurometric and Psychometric Detection Performance , 2010, The Journal of Neuroscience.

[12]  E Ahissar,et al.  One whisker whisking: unit recording during conditioned whisking in rats , 2004, Somatosensory & motor research.

[13]  M. Brecht,et al.  Behavioural report of single neuron stimulation in somatosensory cortex , 2008, Nature.

[14]  B. Sakmann,et al.  Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex , 2004, Nature.

[15]  E. Fetz,et al.  Postspike facilitation of forelimb muscle activity by primate corticomotoneuronal cells. , 1980, Journal of neurophysiology.

[16]  D. Tank,et al.  Functional Clustering of Neurons in Motor Cortex Determined by Cellular Resolution Imaging in Awake Behaving Mice , 2009, The Journal of Neuroscience.

[17]  B. Sakmann,et al.  In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain , 2002, Pflügers Archiv.

[18]  Asaf Keller,et al.  Whisker motor cortex ablation and whisker movement patterns , 2003, Somatosensory & motor research.

[19]  R Bermejo,et al.  Discriminative whisking in the head-fixed rat: optoelectronic monitoring during tactile detection and discrimination tasks. , 2001, Somatosensory & motor research.

[20]  D. Katz,et al.  Distinct Subtypes of Basolateral Amygdala Taste Neurons Reflect Palatability and Reward , 2009, The Journal of Neuroscience.

[21]  T. Ono,et al.  Integrated lateral hypothalamic neural responses to natural and artificial rewards and cue signals in the rat , 1985, Brain Research.

[22]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[23]  I. Whishaw,et al.  On the origin of skilled forelimb movements , 2000, Trends in Neurosciences.

[24]  Toshio Iijima,et al.  Impairment of the discrimination of the direction of single-whisker stimulation induced by the lemniscal pathway lesion , 2007, Neuroscience Research.

[25]  H. Zeigler,et al.  Conditioned whisking in the rat. , 1996, Somatosensory & motor research.

[26]  Masataka Watanabe,et al.  Prefrontal unit activity during delayed conditional Go/No-go discrimination in the monkey. I. Relation to the stimulus , 1986, Brain Research.

[27]  J. Tanji,et al.  Gating of motor cortex reflexes by prior instruction. , 1974, Brain research.

[28]  M. Inase,et al.  Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements. , 1991, Journal of neurophysiology.

[29]  B. Sakmann,et al.  Spiking in primary somatosensory cortex during natural whisking in awake head-restrained rats is cell-type specific , 2009, Proceedings of the National Academy of Sciences.

[30]  Masataka Watanabe,et al.  Prefrontal unit activity during delayed conditional Go/No-go discrimination in the monkey. II. Relation to Go and No-go responses , 1986, Brain Research.

[31]  Miguel A. L. Nicolelis,et al.  Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex , 1999, Nature Neuroscience.

[32]  J. Tanji,et al.  Neuronal activities in the primate motor fields of the agranular frontal cortex preceding visually triggered and self-paced movement , 2004, Experimental Brain Research.

[33]  Cornelius Schwarz,et al.  Central signals rapidly switch tactile processing in rat barrel cortex during whisker movements. , 2006, Cerebral cortex.

[34]  Albert K. Lee,et al.  Whole-Cell Recordings in Freely Moving Rats , 2006, Neuron.

[35]  G. Buzsáki,et al.  Maintenance of signal directed behavior in a response dependent paradigm: a systems approach. , 1979, Acta neurobiologiae experimentalis.

[36]  James Danckert,et al.  Attention for action? Examining the link between attention and visuomotor control deficits in a patient with optic ataxia , 2009, Neuropsychologia.

[37]  K. Svoboda,et al.  Neural Activity in Barrel Cortex Underlying Vibrissa-Based Object Localization in Mice , 2010, Neuron.

[38]  Jerí L. Bryant,et al.  A low-cost solution to measure mouse licking in an electrophysiological setup with a standard analog-to-digital converter , 2006, Journal of Neuroscience Methods.

[39]  W T Thach,et al.  On-beam synchrony in the cerebellum as the mechanism for the timing and coordination of movement , 2007, Proceedings of the National Academy of Sciences.

[40]  Tomoki Fukai,et al.  Prototypic Seizure Activity Driven by Mature Hippocampal Fast-Spiking Interneurons , 2010, The Journal of Neuroscience.

[41]  J. Tanji,et al.  Contrasting neuronal activity in supplementary and precentral motor cortex of monkeys. I. Responses to instructions determining motor responses to forthcoming signals of different modalities. , 1985, Journal of neurophysiology.

[42]  J. Travers,et al.  Motor and Premotor Mechanisms of Licking , 1997, Neuroscience & Biobehavioral Reviews.

[43]  Ian Q. Whishaw,et al.  The structure of skilled forelimb reaching in the rat: A proximally driven movement with a single distal rotatory component , 1990, Behavioural Brain Research.

[44]  J. Chapin,et al.  Distinct temporal activity patterns in the rat M1 and red nucleus during skilled versus unskilled limb movement , 2004, Behavioural Brain Research.

[45]  Sean M Montgomery,et al.  Integration and Segregation of Activity in Entorhinal-Hippocampal Subregions by Neocortical Slow Oscillations , 2006, Neuron.

[46]  I. Whishaw,et al.  The Behavior of the Laboratory Rat , 2004 .

[47]  T. Gerdjikov,et al.  Discrimination of Vibrotactile Stimuli in the Rat Whisker System: Behavior and Neurometrics , 2010, Neuron.

[48]  R. Llinás,et al.  Dynamic organization of motor control within the olivocerebellar system , 1995, Nature.

[49]  Maik C. Stüttgen,et al.  Psychophysical and neurometric detection performance under stimulus uncertainty , 2008, Nature Neuroscience.

[50]  C. Petersen,et al.  Correlating whisker behavior with membrane potential in barrel cortex of awake mice , 2006, Nature Neuroscience.

[51]  J. Tanji,et al.  Contrasting neuronal activity in supplementary and precentral motor cortex of monkeys. II. Responses to movement triggering vs. nontriggering sensory signals. , 1985, Journal of neurophysiology.

[52]  Yoshio Maruyama,et al.  Transcranial optogenetic stimulation for functional mapping of the motor cortex , 2009, Journal of Neuroscience Methods.

[53]  J. Tanji,et al.  Role for cingulate motor area cells in voluntary movement selection based on reward. , 1998, Science.

[54]  Maik C. Stüttgen,et al.  Two Psychophysical Channels of Whisker Deflection in Rats Align with Two Neuronal Classes of Primary Afferents , 2006, The Journal of Neuroscience.

[55]  M. Fee,et al.  Active Stabilization of Electrodes for Intracellular Recording in Awake Behaving Animals , 2000, Neuron.

[56]  Maik C. Stüttgen,et al.  The Head-fixed Behaving Rat—Procedures and Pitfalls , 2010, Somatosensory & motor research.

[57]  C. Petersen,et al.  Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Behaving Mice , 2010, Neuron.