Features of Mitochondrial Dynamics Changes in Large Pyramidal Neurons of the Human Motor Cortex during Aging.

Slow and fast groups of pyramidal tract cells and their respective membrane properties.

Fussy mitochondria fuse in response to stress

Multiple brain regions including the amygdala and prefrontal cortex are crucial for modulating fear conditioning and extinction. The primary motor cortex is known to participate in the planning, control, and execution of voluntary movements. Whether and how the primary motor cortex is involved in modulating freezing responses related to fear conditioning and extinction remains unclear. Here we show that inactivation of the mouse primary motor cortex impairs both the acquisition and extinction of freezing responses induced by auditory-cued fear conditioning. Fear conditioning significantly increases the elimination of dendritic spines on apical dendrites of layer 5 pyramidal neurons in the motor cortex. These eliminated spines are further apart from each other than expected from random distribution along dendrites. On the other hand, fear extinction causes the formation of new spines that are located near the site of spines eliminated previously after fear conditioning. We further show that fear conditioning decreases and fear extinction increases somatic activities of layer 5 pyramidal neurons in the motor cortex respectively. Taken together, these findings indicate fear conditioning and extinction induce opposing changes in synaptic connections and somatic activities of layer 5 pyramidal neurons in the primary motor cortex, a cortical region important for the acquisition and extinction of auditory-cued conditioned freezing responses.

Chemogenetic activation of glutamatergic neurons in the motor cortex promotes functional recovery after ischemic stroke in rats

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials’ amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.

in a series P of studies of the relation of discharge 01 pyramlda1 tract neurons (PTNs) to voluntary movement. The first of the previous studies (5) showed that PTN activity both at rest and during movement is related to axonal conduction velocity. PTNs with the highest axonal conduction velocities tend to be silent during motor quiescence and to show phasic activity in association with movement. PTNs with lower axonal conduction velocities are for the most part active even in the absence of movement; with movement they show both upward and downward modulation of their resting discharge frequency. A second study (6) was carried out to obtain information as to the point in the interval between stimulus and response at which PTN discharge takes place in association with a conditioned hand movement. It was found that for many PTNs, responses to the conditioned stimulus (the onset of a light) preceded the first peripheral electromyographic correlates of the conditioned response (wrist extension). The fact that these PTN responses preceded the electromyographic response showed that they were not consequent upon feedback resulting from the movement. 1

Morphology of identified corticospinal cells in the rat following motor cortex injury: absence of use-dependent change

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.

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal gray matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood. In this study, we first characterized the activity patterns of neurons in the primary and secondary motor cortices during emission of USVs in rats using large-scale electrophysiological recordings. We also examined the axonal projection of the motor cortex to PAG using retrograde labeling and identified two clusters of PAG-projecting neurons in the anterior and posterior parts of the motor cortex. The neural activity patterns around the emission of USVs differed between the anterior and posterior regions, which were divided based on the distribution of PAG-projecting neurons in the motor cortex. Furthermore, using optogenetic tagging, we recorded the USV modulation of PAG-projecting neurons in the posterior part of the motor cortex and found that they showed predominantly sustained excitatory responses during USVs. These results contribute to our understanding of the involvement of the motor cortex in the generation of USV at the neuronal and circuit levels.

1. Monkeys were trained to grasp a rod movable in a horizontal arc (Fig. 1), and to hold the rod by angulation of the wrist in each of three positions (A,B, C). A maintained load was placed on the rod alternately to oppose flexion and extension. At a light signal, the monkey had to move to the next position in a prescribed sequence (ABCBABCBA, ETC.). The task was designed to dissociate, while holding in position, the following variables: 1) pattern of muscular activity in the forearm required to hold the wrist in position, determined by the direction of the load (flexor or extensor muscles); 2) position of the rod, and thus angulation of the wrist joint (A, B, and C); and 3) set for the direction of the intended next movement (flexor or extensor). These variables are subsequently referred to as MPAT, JPOS, and DSET, respectively. 2. After training, recordings were made of the EMG activity of muscles used in the task and of the discharge of single neurons in the motor cortex of the cerebrum and the interposed and dentate nuclei of the cerebellum. 3. While holding the wrist in position, EMG and interpositus behaved uniformly, with higher discharge frequency under load in one direction and lower discharge frequency under load in the opposite direction. This relation was relatively independent of the position held and of the direction of the intended next movement. Thus, interpositus and EMG both seemed best related to the MPAT variable, as opposed to JPOS and DSET variables. By contrast, neurons in motor cortex and in dentate fell into three categories: one category discharged in relation to the pattern of muscular activity (MPAT), a second to the position of the wrist (JPOS), and a third to the direction of the intended next movement (DSET). While MPAT neurons formed a distinct dissociated group, neurons that were best related to JPOS were often related to DSET, and vice versa. 4. A few of the MPAT neurons in interpositus and motor cortex were further studied by varying the magnitude (as well as the direction) of the loads. Both interpositus and motor cortex MPAT neurons changed firing frequency in relation to the magnitude of load, and though few neurons were thus studied, the relation seemed clearer for interpositus than for motor cortex. 5. Anatomically, the three types of neurons thus classified by firing pattern during the hold periods were intermixed in the arm area of motor cortex. In dentate and interpositus, those neurons thus related to the performance were localized to a narrow strip across the posterior part of both nuclei. Neurons apparently related to eye and drinking movements were located more posteriorly still, suggesting somatotopic representation.

RELATION OF DISCHARGE FREQUENCY TO CONDUCTION VELOCITY IN PYRAMIDAL TRACT NEURONS.

ABSTRACTBackgroundPrevious studies have shown that rapid eye movement (REM) sleep is important for promoting dendritic spine elimination after fear learning as well as for selectively maintaining new dendritic spines after motor learning. These REM sleep‐dependent synaptic changes were measured on apical dendrites of layer 5 pyramidal neurons. Whether and how REM sleep affects synaptic structural plasticity on other cell types in the cortex remain unclear.MethodsUsed transcranial two‐photon microscopy, we examined the effects of auditory cued fear conditioning (FC) and REM sleep on changes of dendritic spines of layer 2/3 pyramidal neurons in the mouse primary motor cortex.ResultsAuditory cued FC induced significantly higher elimination and formation of dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex over 4 hours. The degree of spine elimination rate was correlated with the freezing response during the 24 hour‐recall test. Notably, REM sleep deprivation after FC prevented dendritic spine elimination, but not formation, of layer 2/3 pyramidal neurons. Furthermore, Ca2+ activity of layer 2/3 pyramidal neurons significantly increased during REM sleep, and that optogenetic blockade of Ca2+‐CaMKII signaling during REM sleep prevented FC‐induced spine elimination.ConclusionThese findings reveal an important role of REM sleep in FC‐induced pruning of dendritic spines of layer 2/3 pyramidal neurons in the motor cortex.

Bilateral chemogenetic activation of intratelencephalic neurons in motor cortex reduces spontaneous locomotor activity in mice

The population of neurons in the cat motor cortex which receives monosynaptic input from a specific functional region of the somatic sensory cortex was identified with the techniques of intracellular recording and staining with HRP. Both pyramidal and nonpyramidal cells located in the superficial layers of the pericruciate cortex responded to stimulation of the sensory cortex with short latency, excitatory postsynaptic potentials. More than half of the labeled cells were classified as pyramidal cells and the remainder as sparsely spinous or aspinous nonpyramidal cells. The characteristics of the EPSP's of the 2 groups of cells, ie. latency, time from beginning to peak and amplitude were found to vary only slightly. The results suggest that input from the sensory cortex impinges upon neurons which may in turn have an excitatory or inhibitory effect on cortico-fugal neurons in the motor cortex.

Long-Range Neuronal Circuits Underlying the Interaction between Sensory and Motor Cortex