Optimal parameters for microstimulation derived forelimb movement thresholds and motor maps in rats and mice

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representations (motor maps) of the motor cortex, and was originally used in cats and the capuchin monkey. In more modern experiments, ICMS has been used in rats and mice to assess and interpret plasticity of motor maps in response to experimental manipulation; however, a systematic determination of the optimal ICMS parameters necessary to derive baseline motor maps in rats and mice has not been published. In the present manuscript, we describe two experiments. We first determined the optimal stimulation frequency, pulse number, neocortical depth, and current polarity to achieve the minimum current intensity (movement threshold) to elicit forelimb movements in rats and mice. We show that experimentally naïve rats and mice differ on several of these ICMS parameters. In the second experiment, we measured movement thresholds and map size in states of enhanced neocortical inhibition by the administration of diazepam, as well as neocortical sensitization as the result of repeated seizures. We conclude that movement thresholds are inversely related to motor map size, and that treatments result in a widespread shift the balance between excitation and inhibition in motor neocortical layer 5 influences both movement thresholds and map size.

[1]  H. Sakata,et al.  Functional Organization of a Cortical Efferent System Examined with Focal Depth Stimulation in Cats , 1967 .

[2]  C. G. Phillips,et al.  Selective excitation of corticofugal neurones by surface‐anodal stimulation of the baboon's motor cortex , 1962, The Journal of physiology.

[3]  M. Diamond,et al.  Somatosensory cortical neuronal population activity across states of anaesthesia , 2002, The European journal of neuroscience.

[4]  E. Jankowska,et al.  Projections of pyramidal tract cells to alpha‐motoneurones innervating hind‐limb muscles in the monkey. , 1975, The Journal of physiology.

[5]  Ignacio Anegon,et al.  Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases , 2009, Science.

[6]  R. Porter,et al.  Focal stimulation of hypoglossal neurones in the cat , 1963, The Journal of physiology.

[7]  B. Kolb,et al.  Differential neuroplastic changes in neocortical movement representations and dendritic morphology in epilepsy‐prone and epilepsy‐resistant rat strains following high‐frequency stimulation , 2004, European Journal of Neuroscience.

[8]  G. Teskey,et al.  Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation , 2004, Neuroscience.

[9]  Niranjan A. Kambi,et al.  Overlapping representations of the neck and whiskers in the rat motor cortex revealed by mapping at different anaesthetic depths , 2007, The European journal of neuroscience.

[10]  N. Young,et al.  Motor map expansion in the pilocarpine model of temporal lobe epilepsy is dependent on seizure severity and rat strain , 2009, Experimental Neurology.

[11]  I. Whishaw,et al.  Transient middle cerebral artery occlusion disrupts the forelimb movement representations of rat motor cortex , 2008, The European journal of neuroscience.

[12]  Marie-H Monfils,et al.  Induction of neocortical long-term depression results in smaller movement representations, fewer excitatory perforated synapses, and more inhibitory synapses. , 2006, Cerebral cortex.

[13]  H. Asanuma,et al.  Peripheral afferent inputs to the forelimb area of the monkey motor cortex: Input-output relations , 2004, Experimental Brain Research.

[14]  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.

[15]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. II. Motor seizure. , 1972, Electroencephalography and clinical neurophysiology.

[16]  B. Kolb,et al.  Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion , 2006, Neuroscience.

[17]  Barry W. Connors,et al.  Widely integrative properties of layer 5 pyramidal cells support a role for processing of extralaminar synaptic inputs in rat neocortex , 2003, Neuroscience Letters.

[18]  S. Wise,et al.  The motor cortex of the rat: Cytoarchitecture and microstimulation mapping , 1982, The Journal of comparative neurology.

[19]  R. S. Waters,et al.  Organization of the Mouse Motor Cortex Studied by Retrograde Tracing and Intracortical Microstimulation (ICMS) Mapping , 1991, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[20]  E. G. Jones,et al.  Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  E. G. Jones,et al.  Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  M. Wiesendanger,et al.  Corticomotoneuronal connections in the rat: Evidence from double‐labeling of motoneurons and corticospinal axon arborizations , 1991, The Journal of comparative neurology.

[23]  A. Arnold,et al.  Further study on the excitation of pyramidal tract cells by intracortical microstimulation , 1976, Experimental Brain Research.

[24]  J. Kleim,et al.  Motor Learning-Dependent Synaptogenesis Is Localized to Functionally Reorganized Motor Cortex , 2002, Neurobiology of Learning and Memory.

[25]  H. Asanuma,et al.  Topographical organization of cortical efferent zones projecting to distal forelimb muscles in the monkey , 2004, Experimental Brain Research.

[26]  K. Kurata,et al.  Quantitative analyses of thalamic and cortical origins of neurons projecting to the rostral and caudal forelimb motor areas in the cerebral cortex of rats , 1998, Brain Research.

[27]  E. Neafsey,et al.  A second forelimb motor area exists in rat frontal cortex , 1982, Brain Research.

[28]  G. Teskey,et al.  Repeated seizures lead to altered skilled behaviour and are associated with more highly efficacious excitatory synapses , 2008, The European journal of neuroscience.

[29]  J. Kleim,et al.  The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture. , 2011, Cerebral cortex.

[30]  T. Sloan,et al.  Anesthetic effects on electrophysiologic recordings. , 1998, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[31]  D. Purpura,et al.  INTRACELLULAR ACTIVITIES AND EVOKED POTENTIAL CHANGES DURING POLARIZATION OF MOTOR CORTEX. , 1965, Journal of neurophysiology.

[32]  Larry W. Swanson,et al.  Brain Maps: Structure of the Rat Brain , 1992 .

[33]  Andrew R. Brown,et al.  Motor maps, seizures, and behaviour. , 2008, Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale.

[34]  G. Teskey,et al.  Reduction of seizure thresholds following electrical stimulation of sensorimotor cortex is dependent on stimulation intensity and is not related to synaptic potentiation , 2007, Neuroscience.

[35]  Ian Q Whishaw,et al.  Evidence for bilateral control of skilled movements: ipsilateral skilled forelimb reaching deficits and functional recovery in rats follow motor cortex and lateral frontal cortex lesions , 2004, The European journal of neuroscience.

[36]  R. Racine,et al.  Effects of procaine hydrochloride, diazepam, and diphenylhydantoin on seizure development in cortical and subcortical structures in rats. , 1975, Electroencephalography and clinical neurophysiology.

[37]  Jenni M. Karl,et al.  Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease , 2008, Brain Research Bulletin.

[38]  J. Kleim,et al.  Functional reorganization of the rat motor cortex following motor skill learning. , 1998, Journal of neurophysiology.

[39]  Marie-H Monfils,et al.  Motor map expansion following repeated cortical and limbic seizures is related to synaptic potentiation. , 2002, Cerebral cortex.

[40]  C. Sherrington Integrative Action of the Nervous System , 1907 .

[41]  I. Whishaw Lateralization and reaching skill related: Results and implications from a large sample of Long-Evans rats , 1992, Behavioural Brain Research.

[42]  N. Young,et al.  Low-frequency stimulation reverses kindling-induced neocortical motor map expansion , 2008, Neuroscience.

[43]  KM Jacobs,et al.  Reshaping the cortical motor map by unmasking latent intracortical connections , 1991, Science.

[44]  N. Young,et al.  Hippocampal Kindling Leads to Motor Map Expansion , 2006, Epilepsia.

[45]  H. Asanuma,et al.  Patterns of contraction of distal forelimb muscles produced by intracortical stimulation in cats. , 1971, Brain research.

[46]  E. Rouiller,et al.  Comparison of the connectional properties of the two forelimb areas of the rat sensorimotor cortex: support for the presence of a premotor or supplementary motor cortical area. , 1993, Somatosensory & motor research.

[47]  I. Whishaw,et al.  Quantitative and Qualitative Impairments in Skilled Reaching in the Mouse (Mus musculus) After a Focal Motor Cortex Stroke , 2002, Stroke.

[48]  M. Merzenich,et al.  Repetitive microstimulation alters the cortical representation of movements in adult rats. , 1990, Somatosensory & motor research.

[49]  F. Martin,et al.  Comparison of the effects of sevoflurane and propofol on cortical somatosensory evoked potentials. , 2002, British journal of anaesthesia.

[50]  T. Jones,et al.  Unilateral Sensorimotor Cortex Lesions in Adult Rats Facilitate Motor Skill Learning with the “Unaffected” Forelimb and Training-Induced Dendritic Structural Plasticity in the Motor Cortex , 2002, The Journal of Neuroscience.

[51]  Marie-H Monfils,et al.  In Search of the Motor Engram: Motor Map Plasticity as a Mechanism for Encoding Motor Experience , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[52]  M. Merzenich,et al.  Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  R. Hall,et al.  Organization of motor and somatosensory neocortex in the albino rat , 1974 .

[54]  J. Kleim,et al.  Long-term potentiation induces expanded movement representations and dendritic hypertrophy in layer V of rat sensorimotor neocortex. , 2004, Cerebral cortex.

[55]  W. D. Thompson,et al.  Excitation of pyramidal tract cells by intracortical microstimulation: effective extent of stimulating current. , 1968, Journal of neurophysiology.

[56]  M. Schwab,et al.  Cells of origin, course, and termination patterns of the ventral, uncrossed component of the mature rat corticospinal tract , 1997, The Journal of comparative neurology.

[57]  J. B. Ranck,et al.  Which elements are excited in electrical stimulation of mammalian central nervous system: A review , 1975, Brain Research.