The Match Between Natural Neuronal Properties and Stimulation-Evoked Movement

To investigate the electrophysiological properties of pyramidal neurons in mouse motor cortex during the early postnatal development. Thirty-six mice were randomly divided into postnatal 1-, 2-, 3-Week and 1-, 2-,3-Month groups (n=6). Membrane properties, action potentials (AP) and spontaneous excitatory postsynaptic currents (sEPSCs) of motor cortex pyramidal neurons were recorded to evaluate the changes in the intrinsic electrophysilogical characteristics by using whole cell patch clamp. Pyramidal neurons and interneurons were distinguished according to the AP firing patterns. Comparing with interneurons, pyramidal neurons exhibited regular spiking (RS) with smaller frequency. During the period of postnatal 1 Week-3 Months, some of the intrinsic membrane properties of motor cortex pyramidal neurons changed. Compared to the 1-Week mice, the resting membrane potential (RMP) of 2-Week decreased significantly (P＜0.01), and the membrane input resistance (Rin) of 1-Month got a hyperpolarization (P＜0.01), and they showed no significant change in the next period, while the membrane capacitance (Cm) showed no significant changes during the whole postnatal development. The AP dynamic properties changed significantly during this period. Compared to the 1-Week mice, the absolute value of the AP threshold and the AP amplitude of the 3-Week increased significantly (P＜0.01), while the spike half width of the 2-Week decreased substantially (P＜0.05), and they showed no significant change in the next period. The sEPSCs frequency and amplitude of 1- Month increased significantly compared to the 1-Week mice(P＜0.01), while during the period of next 1 Month-3 Months, the amplitude and frequency showed no significant change. These results suggest that the motor cortex pyramidal neurons have time-specific eletrophysilogical properties during the postnatal development. The electrophysiological properties can be used as a functional index to detect the degree of neurons maturity, and as a marker to distinguish the pyramidal neurons and interneurons.

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5-7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICF. The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex.

Differences in excitability of cortical neurons as a function of motor projection in conditioned cats.

1. The experiments were designed to investigate the effects of longitudinal muscle displacements on neurones of the motor cortex of anaesthetized Cebus monkeys and thus test the hypothesis that signals from muscle spindles may modify motor cortical output. The effects of sinusoidal stretching of the extensor digitorum communis (EDC) at frequencies varying from 6 to 300 Hz and of step and rhomboidal stretches were studied in neurones of the motor cortex. For comparison, neurones of the primary receiving area for low-threshold muscle afferents, cortical area 3a, were also included in this study. Neurones of the motor cortex were subdivided into corticospinal (PT) neurones and non-corticospinal (non-PT) neurones. 2. Threshold stretch amplitudes were clearly higher for neurones of area 4 (PT and non-PT) than for 3a neurones. However, a conspicuous fall in threshold stretch amplitude was observed for all three neurone populations when the frequency of sinusoidal stretching was increased (highest frequency: 300 Hz). A small number of non-PT and PT neurones responded to vibration amplitudes of less than 100 mum and some of these low-threshold cells of area 4 also responded to rhomboidal stretches of 8 mm/sec ramp velocity and 80 mum plateau amplitude. Increasing the stretch amplitude to twice threshold nearly doubled the output magnitude in all three cell types. Neurones of area 3a and non-PT neurones of area 4 had similar latencies, and these were significantly shorter than the latencies of PT neurones tested with trains of high frequency vibration. Dynamic response patterns were observed in all three cell types, but most frequently in 3a neurones. 3. It is concluded that, in Cebus monkeys, signals from both primary and secondary muscle spindle endings from forelimb muscles reach the motor cortex. Under the present experimental conditions, the input from the primaries to the motor cortex was effective only if these spindle receptors were driven maximally by vibratory stimuli. The particularly low probability of stretch-evoked discharges of cortico-spinal neurones in the anaesthetized preparation may be explained by a low gain in transmission from input to output cells of the motor cortex.

Motor Cortex

1. We have recently demonstrated that reversible, cooling-induced inactivation of the face motor cortex results in a severe impairment in the ability of monkeys (Macaca fascicularis) to perform a tongue-protrusion task but produces only relatively minor effects on the performance of a biting task by the same monkeys. To establish a neuronal correlate for these different behavioral relations, the present study has detailed the afferent input and intracortical microstimulation (ICMS)-defined output features of a population of face motor cortical neurons, and in a subsequent study we have documented the activities of the same population of neurons during the performance of the tongue-protrusion and biting tasks. 2. Of the 231 single neurons recorded within the face motor cortex, 163 were located at sites from which ICMS (less than or equal to 20 microA) could evoke tongue movements (i.e., "tongue-MI" sites) at the lowest threshold for eliciting orofacial movements. The remainder were located at sites from which ICMS evoked jaw movements ("jaw-MI" sites), face movements ("face-MI" sites), or at a few sites, tongue movements and, at the same threshold intensity, either a jaw movement or a facial movement. 3. We confirmed the general organizational features of the face motor cortex that have been defined in previous studies, but we documented in detail the organizational features for tongue-MI. Thus we found that tongue movements were well represented, whereas jaw-closing movements were poorly represented; the representations for face, jaw, and tongue movements were overlapped; the same ICMS-evoked tongue movement could be multiply represented within tongue-MI; tongue-MI was characterized by a prominent input from superficial mechanosensory afferents, whereas there was little evidence for deep input; a close spatial match was found between ICMS-defined motor output and somatosensory afferent input for tongue-MI. 4. A variety of tongue movements could be evoked by ICMS at tongue-MI sites and were categorized into protrusion, retrusion, laterally directed, and other types of tongue movement. Low-threshold (i.e., less than or equal to 5 microA) ICMS-defined tongue-MI sites, which were considered to represent "efferent zones" projecting relatively directly to motoneurons, were reconstructed three dimensionally to provide insights into the spatial organization of tongue-MI. Examples of each of the four low-threshold efferent-zone categories were usually found throughout the ICMS-defined tongue-MI without any apparent preferential distribution. Furthermore, different low-threshold efferent-zone categories had close spatial relationships to each other in cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

In sensory cortical networks, peripheral inputs differentially activate excitatory and inhibitory neurons. Inhibitory neurons typically have larger responses and broader receptive field tuning compared with excitatory neurons. These differences are thought to underlie the powerful feedforward inhibition that occurs in response to sensory input. In the motor cortex, as in the somatosensory cortex, cutaneous and proprioceptive somatosensory inputs, generated before and during movement, strongly and dynamically modulate the activity of motor neurons involved in a movement and ultimately shape cortical command. Human studies suggest that somatosensory inputs modulate motor cortical activity in a center excitation, surround inhibition manner such that input from the activated muscle excites motor cortical neurons that project to it, whereas somatosensory input from nearby, nonactivated muscles inhibit these neurons. A key prediction of this hypothesis is that inhibitory and excitatory motor cortical neurons respond differently to somatosensory inputs. We tested this prediction with the use of multisite extracellular recordings in anesthetized rats. We found that fast-spiking (presumably inhibitory) neurons respond to tactile and proprioceptive inputs at shorter latencies and larger response magnitudes compared with regular-spiking (presumably excitatory) neurons. In contrast, we found no differences in the receptive field size of these neuronal populations. Strikingly, all fast-spiking neuron pairs analyzed with cross-correlation analysis displayed common excitation, which was significantly more prevalent than common excitation for regular-spiking neuron pairs. These findings suggest that somatosensory inputs preferentially evoke feedforward inhibition in the motor cortex. We suggest that this provides a mechanism for dynamic selection of motor cortical modules during voluntary movements.

The generation and control of reaching in space is a function of several structures, cortical and subcortical. This paper summarizes some principles of the cortical mechanisms subserving this function, as revealed by recording the impulse activity of neurons in motor cortex and area 5 of the posterior parietal cortex in behaving monkeys. Large populations of neurons in these cortical areas are engaged in reaching. This engagement is early in time; for example, cell activity in the motor cortex begins to change 60-80 ms after target onset, and slightly later in area 5. The time course of cell recruitment in the active population is very similar for reaching movements of equal amplitude directed to different targets. In contrast, the intensity of cell discharge in both motor and parietal cortex is clearly modulated with respect to the direction of reaching. Typically, the firing rate is a cosine function of the direction of the movement in space. An unambiguous distributed code for the direction of reaching exists in neuronal populations in the cortical areas studied. The outcome of this population code can be visualized as a vector in neural space that points in the direction of the upcoming movement.

Sex differences in somatic and sensory motor development after neonatal anoxia in Wistar rats

Sensory and motor responses of precentral cortex cells during comparable passive and active joint movements.

A potential treatment for paralysis resulting from spinal cord injury is to route control signals from the brain around the injury via artificial connections. Such signals could then control electrical stimulation of muscles, thereby restoring volitional movement to paralyzed limbs1–3. In previously separate experiments, activity of motor cortex neurons related to actual or imagined movements has been used to control computer cursors and robotic arms4–10, and paralyzed muscles have been activated by functional electrical stimulation (FES)11–13. Here we show that monkeys can directly control stimulation of muscles using the activity of neurons in motor cortex, thereby restoring goal-directed movements to a transiently paralyzed arm. Moreover, neurons could control functional stimulation equally well regardless of any prior association to movement, a finding that significantly expands the source of control signals for brain-machine interfaces. Monkeys learned to utilize these artificial connections from cortical cells to muscles to generate bidirectional wrist torques, and controlled multiple neuron-muscle pairs simultaneously. Such direct transforms from cortical activity to muscle stimulation could be implemented by autonomous electronic circuitry, creating a relatively natural neuroprosthesis. These results are the first demonstration that direct artificial connections between cortical cells and muscles can compensate for interrupted physiological pathways and restore volitional control of movement to paralyzed limbs.

1. In previous papers we presented evidence pointing to an important role for face motor cortex in the control of tongue movements. Intracortical microstimulation (ICMS) at many sites within face motor cortex evoked different types of tongue movement, and many neurons at these "tongue-MI" sites received intraoral mechanosensitive afferent input, and their activity was related to a tongue-protrusion task performed by a monkey. In view of the synergistic action of the various tongue muscles during tongue movement, we hypothesized that these different tongue-MI sites are recruited to effect the appropriate change in tongue shape and position during a tongue-protrusion movement. A prediction from this hypothesis is that variations in the direction of a tongue-protrusion movement should be associated with variations in the activities within the different tongue-MI efferent zones. Differences in efferent-zone activity should be reflected in differences in the firing rates of neurons that are located at these tongue-MI sites. 2. We trained two monkeys to perform a tongue-protrusion task at each of three directions. The tongue-protrusion task transducer was positioned at 0 degrees (Ts), 30 degrees to the left (Tlt), or 30 degrees to the right (Trt) from the midsagittal plane; the latter two positions were termed asymmetric tongue-protrusion task positions. Single neurons were recorded from tongue-MI during trials of tongue-protrusion task at each of two or three of the above positions. Some of the neurons were also studied during a biting task. In addition, neurons were tested for possible mechanosensitive afferent input. 3. Of the 66 neurons studied, 31 (45%) exhibited directional relations; that is, the change in firing rate between the pretrial period (PTP) and the task period for the tongue-protrusion task was significantly different for each neuron depending on the direction in which the activity of the neuron was studied. 4. The "directional" neurons exhibited a single preferred direction of firing in that the mean firing rate during one direction of tongue-protrusion task was significantly greater than for any other direction. Of the 20 neurons studied at all three directions of tongue-protrusion task, the mean firing rate of each of 18 was highest at one of the asymmetric positions, and 12 of these 18 neurons exhibited a monotonic decrease in absolute firing frequency from one asymmetric task direction to the other. 5. Thirteen of the neurons were also studied while the monkey performed the biting task. Most tongue-MI directional neurons were not related to the biting task.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The previous paper has described in detail the input and output features of single neurons located at sites within primate face motor cortex from which intracortical microstimulation (ICMS, less than or equal to 20 microA) evoked tongue movements at the lowest threshold ("tongue-MI" sites); for comparative purposes, we also reported on the input and output features of a smaller number of neurons recorded at sites from which ICMS could evoke jaw movements ("jaw-MI" sites), facial movements ("face-MI" sites), or, at a few sites, tongue movements and, at the same threshold intensity, either a jaw movement or a facial movement. 2. Our findings of an extensive and diverse representation of sites within face motor cortex of monkeys for the generation of elemental components of tongue movement, and the relatively few sites from which jaw-closing movements could be evoked, were consistent with our recent observations that reversible, cooling-induced inactivation of the face motor cortex severely impaired the performance by monkeys of a tongue-protrusion task but had only relatively minor effects on the performance of a biting task. In an attempt to establish a neuronal correlate for these different behavioral relations, the present study has documented the task-related activities of those single neurons that were characterized in the previous paper in terms of afferent input and ICMS-defined output features. 3. Each task required the development and maintenance by each monkey of a fixed force level for a minimum period of time to obtain a fruit-juice reward. During one or both of these tasks, we characterized the activities of 231 single face motor cortical neurons that were located at the above-mentioned ICMS-defined sites. Neurons were said to be related to a particular task if they showed statistically significant differences in firing rates during the task in comparison with a control pretrial period (PTP). 4. In tongue-MI, there was a significantly higher proportion of neurons (63% of 156 neurons tested) that were related to the tongue-protrusion task than to the biting task (15% of 65). However, in jaw-MI the proportion of neurons that were biting task-related (63% of 19) was significantly higher than the proportion related to the tongue-protrusion task (11% of 9); the proportion of biting task-related neurons at ICMS-defined jaw-closing sites was also higher than that at jaw-opening sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Corticospinal Circuits from the Sensory and Motor Cortices Differentially Regulate Skilled Movements through Distinct Spinal Interneurons

1. Extracellular recordings were made in three monkeys while recording from neurones in the motor cortex (eighty-four cells), ventro-posterior lateralis pars caudalis (VPLc, forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. This experiment was designed to produce active and reflex movements of varying velocities in order to study the relationship between amplitude of velocity and magnitude of neuronal discharge of thalamic neurones. The active movements were voluntary rapid alternating movements (RAMs) of the wrist and the reflex movements were produced by forcibly oscillating the wrist joint between frequencies of 1 and 7 Hz (forced oscillations). 3. This study was also designed to examine cerebellar influences on a reflex path, namely the transcortical reflex loop. Forced oscillations were predicted to provide circumstances where active damping was required to prevent excessive oscillations in the reflex path. Rapid alternating movements of the wrist were predicted to provide circumstances where oscillations at the natural frequency in that reflex path would support and propagate the movements. 4. Forced oscillations from 1 to 7 Hz produced movements of different velocities. VPLc and cerebellar thalamic neurones discharged in relation to the duration of movement in a particular direction, but their discharge levels were unrelated to the magnitude of the velocity. Motor cortex neurones fired in a pattern which was related to the timing but not the magnitude of the acceleration. 5. In forced oscillations of the wrist the resonant frequency was between 3 and 7 Hz. They may be controlled in part by a transcortical reflex. The cerebellar thalamic neurones did not fire before motor cortex neurones. Therefore, it is unlikely that the cerebello-thalamo-cortical pathway is necessary to damp these potentially unstable oscillations by an effect on antagonist-related cortical neurones. 6. Rapid alternating movements (RAMs) of monkeys' wrists were performed in a stereotyped fashion over a narrow range of frequencies with the greatest displacement in joint angle and peak velocity at the natural frequency of 3-5 Hz. 7. During the performance of RAMs, neuronal discharge modulated sinusoidally in the VPLc, cerebellar thalamus and motor cortex. There was no relationship between velocity and neuronal discharge of the cerebellar thalamic and motor cortical neurones but there did appear to be a relationship between velocity and VPLc neuronal discharge. 8. The onset of electromyogram (EMG) discharge changed earlier than neuronal discharge in the motor cortex and thalamus during the performance of RAMs.(ABSTRACT TRUNCATED AT 400 WORDS)