Expression of voltage-dependent sodium and transient potassium currents in an identified sub-population of dorsal root ganglion cells acutely isolated from 12-day-old mouse embryos

The electrophysiological properties of a subset of dorsal root ganglion (DRG) neurons microdissected from 12-day-old (E12) mouse embryos and acutely isolated were analyzed as soon as 3 after their isolation. Two classes of neurons were defined according to their mean diameter. The larger diameter class was examined in this study. They display uniform cytoskeletal properties with co-expression of vimentin and neurofilament triplet proteins. Patch-clamp methods also revealed a homogeneous and limited repertoire of ionic channels that included (1) a TTX-sensitive Na⁺ current whose properties are similar to that reported in mature mammalian neurons, and (2) two types of K⁺ currents that can be compared with the delayed rectifier (I _k ) and the transient (I _a) potassium currents found in other mammalian preparations. It may be possible to use this in vitro model to examine the development of new types of currents, such as Ca²⁺ currents during neuronal growth and differentiation.     

Normal aging decreases regional homogeneity of the motor areas in the resting state

Our knowledge about aging modulation of the central motor system remains sparse and contradictory. In the current study, we used functional MRI (fMRI) to study the aging influence on regional homogeneity of the motor-related brain areas in the resting state. We found that regional homogeneity in extensive motor regions, like the cingulate motor area, cerebellum, primary motor cortex, premotor area, supplementary motor area, thalamus, globus pallidus and putamen was significantly decreased in aged subjects. Our study indicates that normal aging process may disrupt the function of motor areas in the resting state, which may contribute to the declined motor ability in aged population.     

Electrophysiological analysis of a sensorimotor integration task

The present experiment aimed at investigating electrophysiologic changes observed as beta band asymmetry, by Quantitative Electroencephalography (qEEG), when individuals performed a reaching motor task (catching a ball in free fall). The sample was composed of 23 healthy individuals, of both sexes, with ages varying between 25 and 40 years old. All the subjects were right handed. A two-way ANOVA was applied for the statistical analysis, to verify the interaction between task moment (i.e., 2 s before and 2 s after ball's fall) and electrode (i.e., frontal, central and temporal regions). The first analysis compared electrodes placed over the somatosensory cortex. Central sites (C3–C4) were compared with temporal regions (T3–T4). The results showed a main effect for moment and position. The second analysis was focused over the premotor cortex, which was represented by the electrodes placed on the frontal sites (F3–F4 versus F7–F8), and a main effect was observed for position. Taken together, these results show a pattern of asymmetry in the somatosensory cortex, associated with a preparatory mechanism when individuals have to catch an object during free fall. With respect to task moment, after the ball's fall, the asymmetry was reduced. Moreover, the difference in asymmetry between the observed regions were related to a supposed specialization of areas (i.e., temporal and central). The temporal region was associated with cognitive processes involved in the motor action (i.e., explicit knowledge). On the other hand, the central sites were related to the motor control mechanisms per se (i.e., implicit knowledge). The premotor cortex, represented by two frontal regions (i.e., F3–F4 versus F7–F8), showed a decrease on neural activity in the contralateral hemisphere (i.e., to the right hand). This result is in agreement with other experiments suggesting a participation of the frontal cortex in the planning of the apprehension task. This sensorimotor paradigm may contribute to the repertoire of tasks used to study clinical conditions such as depression, alzheimer and Parkinson diseases.     

Cervical muscle response to trunk flexion in whiplash-type lateral impacts

The purpose of this study was to determine the response of the cervical muscles to increasing low-velocity, whiplash-type lateral impacts when the occupant is seated out of the recommended driving position (neutral posture). Twenty healthy volunteers were subjected to left lateral impacts of 4.1, 7.7, 10.5, and 13.7 m/s² acceleration, with their trunk flexed by 45° and laterally flexed to the right and left also by 45° at the time of impact. Bilateral electromyograms of the sternocleidomastoids, trapezii, and splenii capitis were recorded. Under these conditions of trunk-flexed postures, in a left lateral impact, muscle responses were of generally low magnitude with the trunk flexed to either the left or right. Even at the highest acceleration of 13.7 m/s², all muscles generated less than 37% of their known maximal voluntary contraction electromyogram. Also, in these left lateral impacts, the right splenius capitis showed a greater EMG response than the left splenius capitis regardless of whether the subject was flexed to the right or left at the time of impact. The right splenius capitis (the one contralateral to the left lateral impact direction) was more active than its counterpart. Compared to what is known for EMG responses with an occupant in the neutral posture, the right sternocleidomastoid (usually the most active muscle in a left lateral collision) was significantly less-active with trunk flexion than with neutral posture conditions (P<0.01). In the absence of bodily impact, the flexed trunk posture does not produce a biomechanical response that would increase the likelihood of cervical muscle injury in low velocity lateral impacts, and may lessen the risk of injury for some muscles.     

The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract

Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions. In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility. Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions). Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders. Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohns disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motility-related disorders. As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.     

Timing of bimanual movements in human and non-human primates in relation to neuronal activity in primary motor cortex and supplementary motor area

It has been established that repeated presentation of a transient target motion stimulus such as a constant-velocity ramp leads to the build up of steady state (SS), anticipatory smooth pursuit eye movements after two or three presentations. Each SS response is then composed of the anticipatory component of nonvisual origin, a visual component associated with the stimulus presentation and another nonvisual component that represents the decay of the response after extinction of the stimulus. Here we investigated the interactions that occur when each motion stimulus was itself a sequence containing more than one ramp component. Ramp components had a velocity of 15 degrees /s or 30 degrees /s to left or right and were separated by gaps of 200 ms duration. In an initial experiment, responses to 2-ramp stimuli were examined and compared with responses to the single-ramp stimuli from which they were constituted. We present evidence that the anticipatory, nonvisual components of the double-ramp response result from the linear summation of the nonvisual components of the responses to the constituent single-ramp components. In a 2nd experiment, we examined responses to a wide variety of 4-ramp sequences and again found evidence that, in the SS, the responses were formed from the linear summation of the constituent single-ramp components. Regression analysis performed on the velocity at onset of each ramp component indicated that this nonvisual part of the response was predictive of the upcoming ramp component. To confirm this, unexpected changes were introduced into single ramp components of the 4-ramp sequence after at least five prior presentations of the sequence had allowed a SS response to be established. Subjects continued to initiate a response to the modified component that was appropriate in velocity and direction for the corresponding part of the previous sequence and inappropriate for the newly modified stimulus. This preprogrammed response persisted unmodified for more than 170 ms after onset of the modified ramp component. In contrast, in the second presentation of the new sequence, the anticipatory component of the response was highly correlated with the SS response of the new sequence, but not with that of the prior sequence, showing that the preprogrammed response had been modified very rapidly. Similar behaviour was observed whichever of the 4-ramp components was modified, indicating that the velocity and direction of the anticipatory response to each component had been preprogrammed. The results suggest that velocity information related to at least four elements of a sequence can be temporarily stored and subsequently released with appropriate temporal order to form an anticipatory response throughout the whole sequence.     

Equalization of asymmetries of tonus in the optomotor system of rabbits

Summary Turning a rabbit on a turn-table for a few degrees induces compensatory eye-movements and results in an asymmetry of tonus in the optomotor system. If the visual input is discontinued (darkness), this asymmetry decays and the eyes drift back to the mid-position within 12–18 sec. The equalization of such asymmetries of tonus under normal conditions and under curare is described. Tonus asymmetries induced by tilting the animals about the longitudinal axis are neither compensated under visual, nor under non-visual, conditions. Recordings were taken from oculomotor neurons, and changes of their firing frequencies were used as a measure for eye movements.A preliminary report was given at the spring meeting of the German Physiological Society 1973.Supported by the Deutsche Forschungsgemeinschaft, SFB 33.     

Comparative Analysis of the Frequency of Neuron Spike Activity in the Sensorimotor Cortex of the Right and Left Hemispheres in Conditions of Immobilization Catatonia in Rabbits

Multineuron activity was recorded from the sensorimotor cortex of the right and left hemispheres during immobilization catatonia in rabbits. The first session of immobilization of the animals was followed by changes in spike frequency in 47% of neurons in the sensorimotor cortex of the right hemisphere. Of these, 30% showed decreases in spike frequency and 17% showed increases. Spike frequency in the sensorimotor cortex of the left hemisphere changed in only 18% of cells, of which 13% showed decreases in spike frequency and 5% showed increases. The spike frequency of neighboring (recorded with the same electrode) neurons could change reciprocally. Differences in neuron activity in the two hemispheres were virtually absent after the second session of immobilization (several days after the first) – spike activity changed in 21% of neurons in the right hemisphere and 24% in the left hemisphere. The ratios of the numbers of neurons with increases and decreases in spike activity in hypnosis also became identical in the cortex of the right and left hemispheres. A hypothesis is proposed for the involvement of cortical neurons in the organization of hypnosis-like states.     

Studies on cortical field potentials recorded during learning processes of visually initiated hand movements in monkeys

Summary A monkey was trained to lift a lever by wrist extension in response to a light stimulus. During the learning process of the task over several months, field potentials related not only to the task performance but also to substitution and stimulation experiments were recorded with chronically implanted electrodes on the surface and at a depth of 2.5–3.0 mm in the prefrontal, premotor, motor and prestriate cortices. In the substitution experiment, an examiner lifted a lever for the monkey so that it was watching the light and rewarded without the hand movement. In the stimulation experiment, the same light stimulus was simply delivered to the monkey. In a naive monkey which lifted the lever independently of the stimulus, stimulus-locked potentials were evoked by the task experiment in those cortices except the motor cortex, but none was elicited by the substitution or stimulation experiment. In a welltrained monkey, the substitution and stimulation experiments induced almost the same potentials as those prior to the task movement in respective cortices except the motor cortex, in which the component of cerebellar-induced premovement potential was not observed during the substitution and stimulation experiments. At an intermediate stage of learning, the situation was intermediate between the naive and well-trained stages and most premovement potentials except those in the motor cortex were elicited by the substitution experiment in reduced sizes, but nothing by the stimulation experiment.The present study suggests that the neuronal circuits for the operantly conditioned movement are functionally organized and gradually consolidated in the learning process, and that the consolidation is made earlier for the circuit involving association and premotor cortices than the circuit including the motor cortex in the process. The circuit to the motor cortex via the cerebro-cerebellar interconnection is recruited only on the execution of movement.     

Ventral specification and perturbed boundary formation in the mouse midbrain in the absence of Hedgehog signaling.

Although Hedgehog (HH) signaling plays a critical role in patterning the ventral midbrain, its role in early midbrain specification is not known. We examined the midbrains of sonic hedgehog (Shh) and smoothened (Smo) mutant mice where HH signaling is respectively attenuated and eliminated. We show that some ventral (Evx1+) cell fates are specified in the Shh-/- mouse in a Ptc1- and Gli1-independent manner. HH-independent ventral midbrain induction was further confirmed by the presence of a Pax7-negative ventral midbrain territory in both Shh-/- and Smo-/- mice at and before embryonic day (E) 8.5. Midbrain signaling centers are severely disrupted in the Shh-/- mutant. Interestingly, dorsal markers are up-regulated (Wnt1, Gdf7, Pax7), down-regulated (Lfng), or otherwise altered (Zic1) in the Shh-/- midbrain. Together with the increased cell death seen specifically in Shh-/- dorsal midbrains (E8.5-E9), our results suggest specific regulation of dorsal patterning by SHH, rather than a simple deregulation due to its absence.