Masticatory motor programs in Australian herbivorous mammals: diprotodontia

Movement of the jaw during molar occlusion is determined by the sequence of activity in the adductor muscles and this sequence is one way to define a masticatory motor program. Based on the similarity of molar structure, it is probable that the American opossum and the early Tertiary mammals that gave rise to all Australian marsupials probably shared a common "primitive" masticatory motor program. The distinct and various patterns of movement of the jaw in the major groups of Australian marsupial herbivores (diprotodontids) are achieved by both subtle and substantial shifts in the timing of the primitive sequence. All diprotodonts divide jaw movements during occlusion into a vertical Phase Im and horizontal Phase IIm, but the number of muscles involved and the level of activity associated with each phase varies considerably. In macropodids (potoroos and kangaroos) Phase Im dominates; in wombats Phase IIm dominates and in koalas the two phases are more evenly divided, with a more equal distribution of muscles between them. The motor program of koalas parallels that of some placental ungulates, while both macropodids and wombats have motor programs unique among mammals.     

Two alternating motor programs drive navigation in Drosophila larva

When placed on a temperature gradient, a Drosophila larva navigates away from excessive cold or heat by regulating the size, frequency, and direction of reorientation maneuvers between successive periods of forward movement. Forward movement is driven by peristalsis waves that travel from tail to head. During each reorientation maneuver, the larva pauses and sweeps its head from side to side until it picks a new direction for forward movement. Here, we characterized the motor programs that underlie the initiation, execution, and completion of reorientation maneuvers by measuring body segment dynamics of freely moving larvae with fluorescent muscle fibers as they were exposed to temporal changes in temperature. We find that reorientation maneuvers are characterized by highly stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers are initiated with head sweeping movement driven by asymmetric contraction of a portion of anterior body segments. The larva attains a new direction for forward movement after head sweeping movement by using peristalsis waves that gradually push posterior body segments out of alignment with the tail (i.e., the previous direction of forward movement) into alignment with the head. Thus, reorientation maneuvers during thermotaxis are carried out by two alternating motor programs: (1) peristalsis for driving forward movement and (2) asymmetric contraction of anterior body segments for driving head sweeping movement.     

Accuracy in estimating motor commands using neuronal population coding

We consider the problem of estimating motor commands from an ensemble of neuronal activities. The population vector algorithm proposed by Georgopoulos provides largely biased estimations when preferred directions of neurons are non-uniformly distributed. To improve this, various decoding methods have been proposed. However, dependence of decoding accuracy on the motor command and other features of neural activities, such as baseline firing rates or amplitudes of tuning curves, have not been quantitatively discussed. In this study, we propose a new method to estimate the motor command in the maximum likelihood estimation framework, which is analytically tractable. We find that the estimation accuracy is independent of the motor command. Using our estimation method, we can estimate the motor command with equal accuracy in all directions.     

Variable initial depolarization in Stein's neuronal model with synaptic reversal potentials

The effect of a variable initial value is examined in Stein's stochastic neuronal model with synaptic reversal potentials under the conditions of a constant threshold and a constant input. The moments of the interspike interval distribution are presented as the functions of the initial depolarization which ranges from inhibitory reversal potential to the threshold potential. Normal, exponential and transformed Gamma distributions are tested for the initial value of depolarization. The coefficient of variation is shown to be greater than one when the initial depolarization is sufficiently above the resting level. An interpretation of this result in the terms of spatial facilitation is offered. The effect of a random initial value is found to be most pronounced for the neurons depolarized to a near threshold level.     

Possible mechanisms of amygdala participation in the regulation of gastric motor activity

Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor reflex activity were studied in electrophysiological and neuroanatomical experiments in Wistar rats. In the anaesthetized animals, electrical stimulation of the CNA affected spontaneous gastric motility and caused inhibitory as well as excitatory changes of vagus-induced gastric relaxation. The most significant and mainly inhibitory effects were observed under the stimulation of the medial CNA. Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA-L) into the different divisions of the CNA revealed direct projections from its dorso-medial portion to the gastric related area of the dorsal vagal complex. Electrical stimulation of this amygdaloid area was found to change activity of the bulbar gastric related neurons. Inhibitory and excitatory changes of their vagus-induced responses under the amigdala stimulation were manifested as a general modulation of all phases of the reaction or a selective modulation of some of them. These mechanisms may underlie the amygdalo-fugal modulation of gastric motor reflex activity.     

A quantitative proteomic analysis of mitochondrial participation in p19 cell neuronal differentiation

A quantitative proteomic analysis of changes in protein expression accompanying the differentiation of P19 mouse embryonal carcinoma cells into neuron-like cells using isobaric tag technology coupled with LC-MS/MS revealed protein changes reflecting withdrawal from the cell cycle accompanied by a dynamic reorganization of the cytoskeleton and an up-regulation of mitochondrial biogenesis. Further study of quantitative changes in abundance of individual proteins in a purified mitochondrial fraction showed that most mitochondrial proteins increased significantly in abundance. A set of chaperone proteins did not participate in this increase, suggesting that neuron-like cells are relatively deficient in mitochondrial chaperones. We developed a procedure to account for differences in recovery of mitochondrial proteins during purification of organelles from distinct cell or tissue sources. Proteomic data supported by RT-PCR analysis suggests that enhanced mitochondrial biogenesis during neuronal differentiation may reflect a large increase in expression of PGC-1alpha combined with down-regulation of its negative regulator, p160 Mybbp1a.     

The effect of dopamine receptor stimulation on the motor and stereotypic activities of mice with different genotypes]

On mice of 8 highly inbred strains--BALB/c, DBA/2, C57B1/6, CBA, DD, CC57Br, C3H/He, A/He--the role was studied of dopamine receptors of the first and second types (D1 and D2) in the regulation of the general motor activity and stereotypic climbing. Significant dependence was shown of these types of dopamine-dependent behaviour on the genotype. Agonist of D1/D2 receptors, apomorphine decreased the motor activity of animals of the all studied strains, and this effect significantly depended on the genotype. The inhibition of locomotion after selective stimulation of D2 receptors (by LY 171555) was significant. Distribution of mouse strains according to expressiveness of climbing after administration of apomorphine differed from their distribution by the level of motor activity. Selective stimulation of D1 receptors, on the whole, elicited climbing of lesser intensity than D1/D2 activation (excluding CBA strain), and administration of D2 agonist did not induce it at all. Probably, for full expression of behavioural reactions the interaction between D1 and D2 receptors is required.     

Regulation and function of neuronal GTP-Ras in facial motor nerve regeneration

Activation of Ras into the GTP-binding, 'ON' state is a key switch in the neurotrophin-mediated neuronal survival and neurite outgrowth, in vitro as well as in vivo . In the current study we explored changes in GTP-Ras levels following facial nerve injury and the ensuing regeneration and the effects of perturbing these changes in vivo using synapsin-promoter mediated neuronal expression of constitutively active Val12H-Ras (synRas). Quantification of GTP-Ras and total Ras revealed a precipitous drop in the relative GTP-Ras levels in the axotomized facial motor nucleus, to 40% of normal levels at 2 days after cut, followed by a partial recovery to 50–65% at 4–28 days. On western blots, control and axotomized nuclei from synRas mutants showed a 2.2- and 2.5-fold elevation in GTP-Ras, respectively, compared with their wild type littermate controls ( p  < 5%, anova , TUKEY post-hoc ), with the levels in the axotomized synRas nucleus slightly but not significantly above that in the uninjured littermate control ( p  = 9.9%). Similar increase was also observed in the pERK but not pAKT targets of the Ras cascade. This moderate elevation of GTP-Ras strongly curtailed post-traumatic neuronal cell death (−65%), the influx of T-cells (−48%) as well as other parameters of neuroinflammatory response. Although synRas did not affect the speed of axonal regeneration or functional recovery it caused a very pronounced increase in central axonal sprouting. These current data emphasize the role of reduced active Ras, and by extension, the reduced overall level of retrograde neurotrophin signalling after axotomy, in mediating post-traumatic cell death and inflammation and in restricting the sprouting response. Moreover, the neuroprotective and central sprouting-enhancing effects of neuronal Val12H-Ras could help promote recovery in CNS injury.     

Rhythmic background thalamic neuronal activity in patients with extrapyramidal motor disorders

The background activity of 123 thalamic neurons was recorded in 30 patients with motor extrapyramidal disorders applying microelectrode techniques to neurosurgical practice. Recordings were taken from the ventro-oral anterior and posterior thalamic nuclei and the adjacent reticular nucleus. A computer analysis was performed of neuronal activity in 44 units and plots produced of autocorrelation and spectral density functions. In patients with parkinsonism and double athetosis, rhythmic activity was found in 48% of cells. A wide variety of regular fluctuations in background neuronal discharges was noted: in the range of theta and delta rhythms (5–7 and 1–4 Hz respectively) with a periodicity of seconds (2–10 sec) and decaseconds (15–40 sec). It was thought possible that several types of regular waves may coexist: phenomena of 2 or 3 accelerated waves and reduced frequency of spike activity of differing periodicity were observed in eight neurons within the same train of spikes. The origin and significance of rhythmically occurring changes in thalamic neuronal spike activity are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR; Institute of Neurosurgery, Ministry of Public Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 19, No. 2, pp. 192–201, March–April, 1987.     

Simultaneous catalepsy and apomorphine-induced stereotypic behavior in mice

Intraventricular administration of haloperidol or chlorpromazine produces catalepsy and blocks apomorphine-induced stereotypic behavior. Low intraventricular doses of domperidone, sulpiride and spiperone, equally cataleptogenic as haloperidol or chlorpromazine, augment rather than diminish stereotypic behavior produced by subsequent apomorphine treatment. The resultant stereotypic behavior continues even while the animal is in a rigid cataleptic posture and is marked by persistent gnawing and licking. Prior to the induction of catalepsy and after recovery from it, mice display the entire range of typical apomorphine-induced behavior including sniffing, climbing, gnawing, and licking. This animal model may be related to the clinical observation of the coexistence of tardive dyskinesia and drug-induced Parkinsonism in individual patients.     

Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein

Overexpression of human alpha-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53-->threonine (A53T) human alpha-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T alpha-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human alpha-synuclein was overexpressed under the control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human alpha-synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.     

Maximization of learning speed in the motor cortex due to neuronal redundancy

Many redundancies play functional roles in motor control and motor learning. For example, kinematic and muscle redundancies contribute to stabilizing posture and impedance control, respectively. Another redundancy is the number of neurons themselves; there are overwhelmingly more neurons than muscles, and many combinations of neural activation can generate identical muscle activity. The functional roles of this neuronal redundancy remains unknown. Analysis of a redundant neural network model makes it possible to investigate these functional roles while varying the number of model neurons and holding constant the number of output units. Our analysis reveals that learning speed reaches its maximum value if and only if the model includes sufficient neuronal redundancy. This analytical result does not depend on whether the distribution of the preferred direction is uniform or a skewed bimodal, both of which have been reported in neurophysiological studies. Neuronal redundancy maximizes learning speed, even if the neural network model includes recurrent connections, a nonlinear activation function, or nonlinear muscle units. Furthermore, our results do not rely on the shape of the generalization function. The results of this study suggest that one of the functional roles of neuronal redundancy is to maximize learning speed.     

Myosin IIC: a third molecular motor driving neuronal dynamics

Neuronal dynamics result from the integration of forces developed by molecular motors, especially conventional myosins. Myosin IIC is a recently discovered nonsarcomeric conventional myosin motor, the function of which is poorly understood, particularly in relation to the separate but coupled activities of its close homologues, myosins IIA and IIB, which participate in neuronal adhesion, outgrowth and retraction. To determine myosin IIC function, we have applied a comparative functional knockdown approach by using isoform-specific antisense oligodeoxyribonucleotides to deplete expression within neuronally derived cells. Myosin IIC was found to be critical for driving neuronal process outgrowth, a function that it shares with myosin IIB. Additionally, myosin IIC modulates neuronal cell adhesion, a function that it shares with myosin IIA but not myosin IIB. Consistent with this role, myosin IIC knockdown caused a concomitant decrease in paxillin-phospho-Tyr118 immunofluorescence, similar to knockdown of myosin IIA but not myosin IIB. Myosin IIC depletion also created a distinctive phenotype with increased cell body diameter, increased vacuolization, and impaired responsiveness to triggered neurite collapse by lysophosphatidic acid. This novel combination of properties suggests that myosin IIC must participate in distinctive cellular roles and reinforces our view that closely related motor isoforms drive diverse functions within neuronal cells.     

Possible participation of nonimpulse factors in the increased excitability of partially deafferentated motor neurons

The dynamics of strengthening of monosynaptic segmental response (MSR) in white rats has been studied after bilateral sciatic nerves cuts nearer to the spinal cord (high cut) and farther from it (low cut). 24 hours after the operation the irritation of the posterior root on the side of the high cut stimulates anterior root MSR of authentically larger amplitude than on the side of the low cut and much greater than in intact animals. 48 h, 72 h and 120 h after the operation MSR amplitude on both sides is considerably increased in comparison with the intact animals amplitude but authentically does not differ on the side of the low and high cuts. A connection may be suggested between the excitability increase process of partially deafferented motoneurons with the disturbance of axoplasmatic flow in central sections of the cut afferent fibres.     

The neuronal NO synthase participation in the peripheral antinociception mechanism induced by several analgesic drugs

The production of nitric oxide (NO) from l-arginine is catalyzed by NO synthase (NOS), which exists as the following three isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). The participation of this pathway in peripheral antinociception has been extensively established by our group with the use of several types of drugs, including opioids, cannabinoids, cholinergic, and α(2C) adrenoceptor agonists and nonsteroidal anti-inflammatory drugs (NSAIDS), and even non-pharmacological procedures such as electroacupuncture. In this study, we aimed to refine the previous data to investigate which type of NOS isoform is involved in the peripheral antinociception mechanism induced by anandamide, morphine, SNC80, bremazocine, acetylcholine, xylazine, baclofen, dipyrone, and diclofenac. After hyperalgesia was induced by intraplantar injection of prostaglandin E(2) in male Wistar rats, we measured peripheral nociception with the paw pressure test. All drugs that were used induced a peripheral antinociception effect that was completely blocked by injection of the selective neuronal NO synthase inhibitor, L-NPA (24μg/paw). The exception was the GABA(B) agonist baclofen, which induced an effect that was not antagonized. We used the inhibitors L-NIO and -NIL (24μg/paw) to exclude the involvement of endothelial and inducible NO synthase, respectively. These drugs were ineffective against the antinociception effect induced by all analgesic drugs that we utilized. Based on the experimental evidence, we conclude that the local injection of analgesic drugs activates nNOS to release NO and induce peripheral antinociception.     

Interactions between the tonic and cyclic postural motor programs in the crayfish abdomen

1. In the crayfish (Procambarus clarkii) abdomen, the superficial flexor and extensor muscles and the motoneurons that innervate them are employed during two completely different modes of behavior: (1) tonic postural adjustments and (2) cyclic movements associated with backwards terrestrial walking. We have tested the possibility that these two behavioral subsystems share at least some of the same tonic premotor interneurons. 2. Of the 108 tonic flexion- and extension-producing interneurons monitored during cyclic pattern generation, only 25 were recruited while 36 were inhibited. None of the recruited interneurons made a measurable contribution to the cyclic motor output. Similarly, none of the 20 inhibitory interneurons of the tonic subsystem recorded in this study was found to play a role in shaping the cyclic motor pattern. 3. Simultaneous activation of single tonic postural interneurons with the cyclic motor pattern revealed that the two behavioral subsystems interact in complex ways. Some tonic interneurons produced motor outputs that overrode the cyclic motor outputs while the motor outputs of other tonic interneurons were completely overwhelmed by the cyclic motor program. Still other tonic interneurons generated motor outputs that predominated over cyclic patterned outputs in some ganglia but were masked by the cyclic motor pattern in other ganglia. 4. Although weak interactions between the two subsystems occur at the premotor level, they have little effect on the normal generation of the cyclic pattern. Stronger interactions apparently occur at the level of the motoneurons and these interactions presumably may form the basis of switching from one behavior to the other. We conclude, therefore, that each behavioral subsystem relies upon its own unique set of premotor interneurons. Finally, those interneurons contributing to the cyclic motor pattern have not yet been identified.     

When a motor goes bad: a kinesin regulates neuronal survival

In this issue of Cell, Midorikawa et al. (2006) demonstrate that the kinesin superfamily member KIF4, a microtubule-based molecular motor, regulates the survival of electrically active neurons in the developing brain by modulating the function of poly(ADP-ribose) polymerase-1 in an unexpected way.     

Aminergic control of neuronal firing rate in thalamic motor nuclei of the rat

The effects induced on neuronal firing by microiontophoretic application of the biological amines noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were studied "in vivo" in ventral-anterior (VA) and ventrolateral (VL) thalamic motor nuclei of anaesthetized rats. In both nuclei the amines had a mostly depressive action on neuronal firing rate, the percentage of units responsive to NA application (88%) being higher than to 5-HT (72%). Short-lasting (less than 2 min) and long lasting (up to 20 min) inhibitory responses were recorded, the former mostly evoked by NA and the latter by 5-HT ejection. In some cases 5-HT application had no effect on the firing rate but modified the firing pattern. NA-evoked responses were significantly more intense in VL than in VA neurons. Short-lasting inhibitory responses similar to NA-induced effects were evoked by the alpha2 adrenergic receptor agonist clonidine and to a lesser extent by the beta adrenergic receptor agonist isoproterenol. Inhibitory responses to 5-HT were partially mimicked by application of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and of the 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine (ALPHA-MET-5-HT). The latter evoked excitatory responses in some cases. Both 5-HT agonists were more effective on VA than on VL neurons. The effects evoked by agonists were at least partially blocked by respective antagonists. These results suggest that although both 5-HT and NA depress neuronal firing rate, their effects differ in time course and in the amount of inhibition; besides aminergic modulation is differently exerted on VA and VL.