Forelimb Region Research Articles

Negative hemodynamic response in the visual cortex: Evidence supporting neuronal origin via hemodynamic observation and two-photon imaging

The positive hemodynamic response (PHR) during stimulation often co-occurs with a strong, sustained negative hemodynamic response (NHR). However, the characteristics and neurophysiological mechanisms of the NHR, especially in regions distal to the PHR, remain incompletely understood. Using intrinsic optical imaging (OI) and two-photon imaging, we observed that forelimb electrical stimulation evoked strong PHR signals in the forelimb region of the primary somatosensory cortex (S1FL). Meanwhile, NHR signals primarily appeared in the primary visual cortex (V1), with a delayed onset and lower amplitude relative to the PHR signals. Additionally, stimulation led to a reduction in cerebral blood flow (CBF) in the NHR region. Notably, there was an overall suppression of the calcium response in the NHR region, although a small proportion (14 %) of neurons exhibited concurrent activation. Axon tracing revealed cortico-cortical projections from S1FL to V1. These findings suggest that neuronal deactivation significantly contributes to the origin of the NHR, offering additional insights into the specific inhibitory mechanisms underlying the NHR.

Effects of washing sanitation standard operating procedures on the microbiological quality and safety of cattle carcasses

Sanitation standard operating procedures (SSOP) are self-control tools used by the food industry to minimize contamination and ensure compliance with quality standards and safety for consumption. SSOPs are implemented in slaughterhouses to reduce or eliminate contamination during the slaughter stage. This work aimed to verify the microbiological effect of SSOP for washing beef carcasses, with pressurized (3 atm) and chlorinated (5 ppm) water from the hind to the front limb. In the forelimb region, groups of indicator microorganisms were quantified, and Salmonella spp., Listeria monocytogenes, pathotypes of diarrheagenic Escherichia coli non-0157, and Staphylococcus aureus with toxigenic potential were investigated in cattle carcasses slaughtered in northern Brazil before and after washing with SSOP. No significant differences (p > 0.05) were observed in the quantification of enterobacteria, mesophilic aerobes, total coliforms, E. coli, and S. aureus after washing with the SSOP. However, were detected Salmonella spp., Shiga toxin-producing (STEC), enteropathogenic (EPEC), and enterotoxigenic (ETEC) E. coli in the sampled carcass regions after washing. S. aureus, potentially producing enterotoxin D, was identified in two carcasses (6.66 %) before and after washing SSOP. Therefore, the SSOP may have spread contamination from other carcass areas to the forequarter region. Therefore, the processes, techniques, and SSOPs carried out at this stage must be reviewed, verified, and monitored to avoid the inclusion of pathogens that could compromise the microbiological safety of carcasses during the pre-washing stages.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway.

Stroke-induced excess in capillarization relative to oxidative capacity in rats is muscle specific.

Stroke is not only associated with muscle weakness, but also associated with reduced muscle fatigue resistance and reduced desaturation during exercise that may be caused by a reduced oxidative capacity and/or microvasculature. Therefore, the objective of the present study was to determine the effects of stroke on muscle mass, fiber size and shape, capillarization and oxidative capacity of the rat m. extensor carpi radialis (ECR) and m. flexor carpi ulnaris (FCU) after a photothrombotic stroke in the forelimb region of the primary sensorimotor cortex. The main observation of the present study was that 4 weeks after induction of stroke there were no significant changes in muscle fiber size and shape. Although there was no significant capillary rarefaction, there was some evidence for remodeling of the capillary bed as reflected by a reduced heterogeneity of capillary spacing (p = 0.006) that may result in improved muscle oxygenation. In the ECR, but not in the FCU, this was accompanied by reduction in muscle fiber oxidative capacity as reflected by reduced optical density of sections stained for succinate dehydrogenase (p = 0.013). The reduced oxidative capacity and absence of significant capillary rarefaction resulted in a capillary to fiber ratio per unit of oxidative capacity that was higher after stroke in the ECR (p = 0.01), but not in the FCU. This suggests that at least during the early stages, stroke is not necessarily accompanied by muscle fiber atrophy, and that stroke-induced reductions in oxidative capacity resulting in relative excess of capillarization are muscle specific.

Метод викликаних потенціалів як перспективний напрямок дослідження ноцицепції у наркотизованих тварин

The sensation of pain is a pathogenetic link in a wide range of diseases, and the study of nociception as its component is an important area of physiology and medicine. However, modern requirements for research conducted using laboratory animals require the search for new approaches to studying nociception and analgesia with minimizing the suffering of subjects in ethological testing and maximizing the transition to instrumental testing. We proposed the use of a standard formalin model of pain in combination with the recording of changes in somatosensory cortex potentials caused by electrical stimulation of efferents at the level of the forelimb. It was found that after subcutaneous injection of 0.30 ml of 4% formalin, the amplitude of evoked potentials increased. Under the conditions of the proposed testing design, both dosedependent and time-dependent effects of the formalin model of pain were observed in an anesthetized animal. The peculiarity of the obtained results was that the fixed somatosensory potentials of the brain in the S1 forelimb region showed sensitivity to the administration of a nociceptive agent in those areas of the body that topographically did not belong to the cortical representation of the forelimbs. This probably indicates the potential universality of this test approach. Thus, it was shown that evoked potentials in the forelimb representation of the primary somatosensory cortex demonstrate a clearly fixed response to painful stimulation in the formalin model of pain and can be used in studies of nociceptive and analgesic effects as a partial alternative to standard ethological testing.

Метод викликаних потенціалів як перспективний напрямок дослідження ноцицепції у наркотизованих тварин

The sensation of pain is a pathogenetic link in a wide range of diseases, and the study of nociception as its component is an important area of physiology and medicine. However, modern requirements for research conducted using laboratory animals require the search for new approaches to studying nociception and analgesia with minimizing the suffering of subjects in ethological testing and maximizing the transition to instrumental testing. We proposed the use of a standard formalin model of pain in combination with the recording of changes in somatosensory cortex potentials caused by electrical stimulation of efferents at the level of the forelimb. It was found that after subcutaneous injection of 0.30 ml of 4% formalin, the amplitude of evoked potentials increased. Under the conditions of the proposed testing design, both dosedependent and time-dependent effects of the formalin model of pain were observed in an anesthetized animal. The peculiarity of the obtained results was that the fixed somatosensory potentials of the brain in the S1 forelimb region showed sensitivity to the administration of a nociceptive agent in those areas of the body that topographically did not belong to the cortical representation of the forelimbs. This probably indicates the potential universality of this test approach. Thus, it was shown that evoked potentials in the forelimb representation of the primary somatosensory cortex demonstrate a clearly fixed response to painful stimulation in the formalin model of pain and can be used in studies of nociceptive and analgesic effects as a partial alternative to standard ethological testing.

Subthalamic Activity for Motor Execution and Cancelation in Monkeys.

The subthalamic nucleus (STN) receives cortical inputs via the hyperdirect and indirect pathways, projects to the output nuclei of the basal ganglia, and plays a critical role in the control of voluntary movements and movement disorders. STN neurons change their activity during execution of movements, while recent studies emphasize STN activity specific to cancelation of movements. To address the relationship between execution and cancelation functions, we examined STN activity in two Japanese monkeys (Macaca fuscata, both sexes) who performed a goal-directed reaching task with a delay that included Go, Cancel, and NoGo trials. We first examined responses to the stimulation of the forelimb regions in the primary motor cortex and/or supplementary motor area. STN neurons with motor cortical inputs were found in the dorsal somatomotor region of the STN. All these STN neurons showed activity changes in Go trials, suggesting their involvement in execution of movements. Part of them exhibited activity changes in Cancel trials and sustained activity during delay periods, suggesting their involvement in cancelation of planed movements and preparation of movements, respectively. The STN neurons rarely showed activity changes in NoGo trials. Go- and Cancel-related activity was selective to the direction of movements, and the selectivity was higher in Cancel trials than in Go trials. Changes in Go- and Cancel-related activity occurred early enough to initiate and cancel movements, respectively. These results suggest that the dorsal somatomotor region of the STN, which receives motor cortical inputs, is involved in preparation and execution of movements and cancelation of planned movements.

Functional and phylogenetic interpretation of the forelimb myology of two South American carnivorans, the ring-tailed coati (Nasua nasua) and crab-eating raccoon (Procyon cancrivorus).

A comparative analysis of the forelimb myology of two neotropical procyonids (Nasua nasua and Procyon cancrivorus) was performed to assess how observed differences in their myological configuration would be related to their diverse ecological behaviors and phylogeny. Although both species are associated with the arboreal substrate, N. nasua is a more agile climber that usually digs; whereas P. cancrivorus spends most of its time on the ground foraging, climbing on the trees as shelter and is a good swimmer. Here, myological descriptions, muscle maps, phylogenetic optimizations, and muscle mass data of the forelimb of these two procyonids are presented. The main functional muscular groups are discussed in a comparative framework with other carnivorans that present a wide ecological diversity. Also, muscular characters were mapped onto a phylogeny to explore their evolution and to obtain ancestral state reconstructions. Results indicate clear myological differences among the two neotropical procyonids associated with their ecological preferences. One of the most remarkable anatomical differences is the arrangement and relative mass of the extrinsic musculature, mainly the musculus rhomboideus and the delto-pectoral complexes. In Nasua nasua, these suggested a greater stability in their shoulder girdle for climbing and digging and probably would provide stronger neck and head movements when they use them for foraging on the ground. Conversely, P. cancrivorus has a different extrinsic muscular configuration, which would allow an increment on the stride length and faster movements of the forelimb associated with more frequent terrestrial gaits. Also, significant differences are observed in the distal musculature, associated with strong movements of forepaws when climbing and digging in N. nasua; whereas, P. cancrivorus configuration suggested precise forearm and digits movements, related to manipulation of food items when they are catching prey or feeding. Most of the codified features of P. cancrivorus would reflect retention of plesiomorphies acquired in the common ancestor of caniforms or arctoids, whereas N. nasua shows derived traits, particularly in the proximal forelimb region. The present work increases the information available on the myology of these particular taxa and extant generalized arctoid models in general. The analyses presented here will be useful both for other comparative myological studies (morpho-functional and phylogenetic) and for muscular reconstruction in extinct procyonids, as well as other carnivorans.

Chemogenetic attenuation of cortical seizures in nonhuman primates

Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool—designer receptors exclusively activated by designer drugs (DREADDs)—for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model.

Factors influencing fault-propagation folding in the Kuqa Depression: Insights from geomechanical models

Understanding the rock mass deformation and strain state is critical to a range of endeavors. Geomechanical modeling is an excellent approach simulating the formation processes of faulting and folding, which can reproduce the geometry of fold structures and track strain and stress through the whole deformation process. In this study, five series of two-dimensional (2D) elastic-plastic finite element models were built to investigate the influences of shortening distance, ramp cutoff angle, interlayer slip, fault friction, fault number and fault slice width on structural styles and strain distribution patterns during fault-propagation folding in the Kuqa Depression of Tarim Basin. The results indicate that, i) All above mentioned factors can influence the structural style and strain distribution of fault-propagation fold (FPF) to varying degrees. Fault friction, interlayer slip and fault slice width are the most important parameters influencing the deformation geometry and strain patterns of FPF; ii) There are critical values for fault friction coefficient and shortening distance to create a secondary fold besides the FPF; iii) A “step pattern” occurs both in the forelimb and backlimb of the FPF when fault slice width reaches a certain high value; iv) Structural position in the FPF controls volumetric changes. The evolution of FPF can be divided into two stages: layer parallel shortening and volume loss, and folding; v) The steep forelimb region of FPF develops more natural fractures, which may serve as a favorable location for potential reservoirs in the Kuqa Depression. The results are also expected to provide clues for the exploration and development of oil and gas in regions with similar geological conditions.

Visible CCD Camera-Guided Photoacoustic Imaging System for Precise Navigation during Functional Rat Brain Imaging

In photoacoustic (PA) imaging, tissue absorbs specific wavelengths of light. The absorbed energy results in thermal expansion that generates ultrasound waves that are reconstructed into images. Existing commercial PA imaging systems for preclinical brain imaging are limited by imprecise positioning capabilities and inflexible user interfaces. We introduce a new visible charge-coupled device (CCD) camera-guided photoacoustic imaging (ViCPAI) system that integrates an ultrasound (US) transducer and a data acquisition platform with a CCD camera for positioning. The CCD camera accurately positions the US probe at the measurement location. The programmable MATLAB-based platform has an intuitive user interface. In vitro carbon fiber and in vivo animal experiments were performed to investigate the precise positioning and imaging capabilities of the ViCPAI system. We demonstrated real-time capturing of bilateral cerebral hemodynamic changes during (1) forelimb electrical stimulation under normal conditions, (2) forelimb stimulation after right brain focal photothrombotic ischemia (PTI) stroke, and (3) progression of KCl-induced cortical spreading depression (CSD). The ViCPAI system accurately located target areas and achieved reproducible positioning, which is crucial in animal and clinical experiments. In animal experiments, the ViCPAI system was used to investigate bilateral cerebral cortex responses to left forelimb electrical stimulation before and after stroke, showing that the CBV and SO2 in the right primary somatosensory cortex of the forelimb (S1FL) region were significantly changed by left forelimb electrical stimulation before stroke. No CBV or SO2 changes were observed in the bilateral cortex in the S1FL area in response to left forelimb electrical stimulation after stroke. While monitoring CSD progression, the ViCPAI system accurately locates the S1FL area and returns to the same position after the probe moves, demonstrating reproducible positioning and reducing positioning errors. The ViCPAI system utilizes the real-time precise positioning capability of CCD cameras to overcome various challenges in preclinical and clinical studies.

0131 Theta oscillations during REM sleep synchronize behavior and neural activity in the developing motor system

Abstract Introduction Myoclonic twitches are abundantly produced during REM sleep in skeletal muscles across the body. In infant rats, movements are produced by the red nucleus (RN), with the RN both sending motor commands and receiving sensory feedback from twitches. The RN’s role in producing twitches contrasts with that of primary motor cortex (M1), which does not generate motor commands at early postnatal ages. Instead, M1 functions as a sensory structure, processing sensory feedback from self-generated movements, including twitches. By postnatal day (P) 12, the RN (but not M1) also begins to exhibit a continuous theta rhythm (~6 Hz) during REM sleep that promotes sensorimotor integration with other brain areas. Given that the RN and M1 collaborate to control movement in adult rats, we hypothesized that theta emerges in M1 after P12, at which time theta synchronizes M1 and RN activity. Methods To determine if and when theta synchronizes activity in the RN and M1, we recorded local field potentials and unit activity in the RN and the forelimb region of M1 in unanesthetized preweanling rats at P12 and P20. Rats were head-fixed but were able to locomote and cycle freely between sleep and wake. Results Neurons in the RN and M1 continued to respond to twitches through P20. Further, as predicted, we observed the developmental emergence of REM-associated theta oscillations in M1 by P20 that were coherent with theta in the RN. Additionally, neural activity was phase-locked to theta; surprisingly, twitches were also phase-locked to theta, with twitches being more likely during the troughs of the oscillation. Finally, the temporal relationship between twitch-related activity in the two structures depended on the phase of theta, with twitch-related activity in M1 lagging behind twitch-related activity in the RN in the rising phase of theta. However, in the falling phase of theta, twitch-related activity in the RN and M1 showed similar time courses. Conclusion These results show how theta during REM sleep promotes the developmental integration of behavior with neural activity in the RN and M1. Because synchronous activity strengthens synaptic connectivity, and theta synchronized twitch-related activity in the RN and M1, these results also implicate twitches and twitch-related activity in the development of somatotopically precise functional connectivity between the RN and M1. Support (If Any) R37-HD081168 to M.S.B. and SRSF Career Development Award to J.C.D.

Chronic oral olanzapine treatment but not haloperidol decreases [3H] MK-801 binding in the rat brain Independent of dietary conditions

Haloperidol and olanzapine are first and second-generation antipsychotic (neuroleptic) medications approved to treat schizophrenia. Glutamate signaling is known to play an important role in the manifestation of schizophrenia symptoms, as phencyclidine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, replicates and exasperates these symptoms. While initial reports show that neuroleptic treatments can impact aspects of NMDAR expression, there is little attention on the interaction between neuroleptics and dietary conditions. Thus, we examined the impact of chronic haloperidol and olanzapine treatment under both normal and high-fat dietary conditions on NMDAR expression. Adult male rats were treated for 28-days with either oral vehicle, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg), and fed either a standard control diet or a high-fat diet. In-vitro receptor autoradiography binding was performed using [3H] MK-801 as a measure of NMDAR expression. Results showed that olanzapine, irrespective of the diet, significantly decreased [3H] MK-801 binding within the cingulate cortex, substantia nigra, insular cortex, piriform cortex, ectorhinal cortex and perirhinal cortex, the forelimb region of the somatosensory cortex, and all quadrants of the caudate-putamen. In contrast, haloperidol treatment did not impact [3H] MK-801 binding, and we also report no effect of diet on [3H] MK-801 binding. These data suggest that the effects seen in olanzapine treatment are not mediated by diet, nor does a 28-day chronic high-fat diet alter [3H] MK-801 binding. Furthermore, these data also importantly support that combined consumption of a high-fat diet and pharmacological treatments are not immediately detrimental to NMDARs and contribute to the expansive literature of precision medicine.

Cerebro-cerebellar interactions in nonhuman primates examined by optogenetic functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is a promising approach for the simultaneous and extensive scanning of whole-brain activities. Optogenetics is free from electrical and magnetic artifacts and is an ideal stimulation method for combined use with fMRI. However, the application of optogenetics in nonhuman primates (NHPs) remains limited. Recently, we developed an efficient optogenetic intracortical microstimulation method of the primary motor cortex (M1), which successfully induced forelimb movements in macaque monkeys. Here, we aimed to investigate how optogenetic M1 stimulation causes neural modulation in the local and remote brain regions in anesthetized monkeys using 7-tesla fMRI. We demonstrated that optogenetic stimulation of the M1 forelimb and hindlimb regions successfully evoked robust direct and remote fMRI activities. Prominent remote activities were detected in the anterior and posterior lobes in the contralateral cerebellum, which receive projections polysynaptically from the M1. We further demonstrated that the cerebro-cerebellar projections from these M1 regions were topographically organized, which is concordant with the somatotopic map in the cerebellar cortex previously reported in macaques and humans. The present study significantly enhances optogenetic fMRI in NHPs, resulting in profound understanding of the brain network, thereby accelerating the translation of findings from animal models to humans.

Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery

Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.

Sensory Coding of Limb Kinematics in Motor Cortex across a Key Developmental Transition.

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements-especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day 8 (P8), nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich representation of movement long before M1 develops its motor functionality.SIGNIFICANCE STATEMENT Primary motor cortex (M1) plays a fundamental role in the generation of voluntary movements and motor learning in adults. In early development, however, M1 functions as a prototypical sensory structure. Here, we demonstrate in infant rats that M1 codes for the kinematics of self-generated limb movements long before M1 develops its capacity to drive movements themselves. Moreover, we identify a key transition during the second postnatal week in which M1 activity becomes more informationally complex. Together, these findings further delineate the complex developmental path by which M1 develops its sensory functions in support of its later-emerging motor capacities.

Changes in muscle\u2013tendon unit length\u2013force characteristics following experimentally induced photothrombotic stroke cannot be explained by changes in muscle belly structure

PurposeThe aim of this study was to assess the effects of experimentally induced photothrombotic stroke on structural and mechanical properties of rat m. flexor carpi ulnaris.MethodsTwo groups of Young-adult male Sprague–Dawley rats were measured: stroke (n = 9) and control (n = 7). Photothrombotic stroke was induced in the forelimb region of the primary sensorimotor cortex. Four weeks later, muscle–tendon unit and muscle belly length–force characteristics of the m. flexor carpi ulnaris, mechanical interaction with the neighbouring m. palmaris longus, the number of sarcomeres in series within muscle fibres, and the physiological cross-sectional area were measured.ResultsStroke resulted in higher force and stiffness of the m. flexor carpi ulnaris at optimum muscle–tendon unit length, but only for the passive conditions. Stroke did not alter the length–force characteristics of m. flexor carpi ulnaris muscle belly, morphological characteristics, and the extent of mechanical interaction with m. palmaris longus muscle.ConclusionThe higher passive force and passive stiffness at the muscle–tendon unit level in the absence of changes in structural and mechanical characteristics of the muscle belly indicates that the experimentally induced stroke resulted in an increased stiffness of the tendon.

Cortical connections of the functional domain for climbing or running in posterior parietal cortex of galagos.

Previous studies in prosimian galagos (Otolemur garnetti) have demonstrated that posterior parietal cortex (PPC) is subdivided into several functionally distinct domains, each of which mediates a specific type of complex movements (e.g., reaching, grasping, hand-to-mouth) and has a different pattern of cortical connections. Here we identified a medially located domain in PPC where combined forelimb and hindlimb movements, as if climbing or running, were evoked by long-train intracortical microstimulation. We injected anatomical tracers in this climbing/running domain of PPC to reveal its cortical connections. Our results showed the PPC climbing domain had dense intrinsic connections within rostral PPC and reciprocal connections with forelimb and hindlimb region in primary motor cortex (M1) of the ipsilateral hemisphere. Fewer connections were with dorsal premotor cortex (PMd), supplementary motor (SMA), and cingulate motor (CMA) areas, as well as somatosensory cortex including areas 3a, 3b, and 1-2, secondary somatosensory (S2), parietal ventral (PV), and retroinsular (Ri) areas. The rostral portion of the climbing domain had more connections with primary somatosensory cortex than the caudal portion. Cortical projections were found in functionally matched domains in M1 and premotor cortex (PMC). Similar patterns of connections with fewer labeled neurons and terminals were seen in the contralateral hemisphere. These connection patterns are consistent with the proposed role of the climbing/running domain as part of a parietal-frontal network for combined use of the limbs in locomotion as in climbing and running. The cortical connections identify this action-specific domain in PPC as a more somatosensory driven domain.

Parallel and Serial Sensory Processing in Developing Primary Somatosensory and Motor Cortex.

It is generally supposed that primary motor cortex (M1) receives somatosensory input predominantly via primary somatosensory cortex (S1). However, a growing body of evidence indicates that M1 also receives direct sensory input from the thalamus, independent of S1; such direct input is particularly evident at early ages before M1 contributes to motor control. Here, recording extracellularly from the forelimb regions of S1 and M1 in unanesthetized rats at postnatal day (P)8 and P12, we compared S1 and M1 responses to self-generated (i.e., reafferent) forelimb movements during active sleep and wake, and to other-generated (i.e., exafferent) forelimb movements. At both ages, reafferent responses were processed in parallel by S1 and M1; in contrast, exafferent responses were processed in parallel at P8 but serially, from S1 to M1, at P12. To further assess this developmental difference in processing, we compared exafferent responses to proprioceptive and tactile stimulation. At both P8 and P12, proprioceptive stimulation evoked parallel responses in S1 and M1, whereas tactile stimulation evoked parallel responses at P8 and serial responses at P12. Independent of the submodality of exafferent stimulation, pairs of S1-M1 units exhibited greater coactivation during active sleep than wake. These results indicate that S1 and M1 independently develop somatotopy before establishing the interactive relationship that typifies their functionality in adults.SIGNIFICANCE STATEMENT Learning any new motor task depends on the ability to use sensory information to update motor outflow. Thus, to understand motor learning, we must also understand how animals process sensory input. Primary somatosensory cortex (S1) and primary motor cortex (M1) are two interdependent structures that process sensory input throughout life. In adults, the functional relationship between S1 and M1 is well established; however, little is known about how S1 and M1 begin to transmit or process sensory information in early life. In this study, we investigate the early development of S1 and M1 as a sensory processing unit. Our findings provide new insights into the fundamental principles of sensory processing and the development of functional connectivity between these important sensorimotor structures.

Rostro-Caudal Specificity of Corticospinal Tract Projections in Mice.

Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex and a region in the dorsolateral cortex near the barrel field (S2). Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the dorsolateral cortex. With injections of biotinylated dextran amine (BDA) into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic sacral levels. With BDA injections into the dorsolateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae and axons from lateral sensorimotor cortex terminated primarily in laminae III-V of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.