A Comparison of the Ipsilateral Cortical Projections to the Dorsal and Ventral Subdivisions of the Macaque Premotor Cortex

The cortical connections of the dorsal (PMd) and ventral (PMv) subdivisions of the premotor area (PM, lateral area 6) were studied in four monkeys (Macaca fascicularis) through the use of retrograde tracers. In two animals, tracer was injected ventral to the arcuate sulcus (PMv), in a region from which forelimb movements could be elicited by intracortical microstimulation (ICMS). Tracer injections dorsal to the arcuate sulcus (PMd) were made in two locations. In one animal, tracer was injected caudal to the genu of the arcuate sulcus (in caudal PMd [cPMd], where ICMS was effective in eliciting forelimb movements); in another animal, it was injected rostral to the genu of the arcuate sulcus (in rostral PMd [rPMd], where ICMS was ineffective in eliciting movements). Retrogradely labeled neurons were counted in the ipsilateral hemisphere and located in cytoarchitectonically identified areas of the frontal and parietal lobes. Although both PMv and PMd were found to receive inputs from other motor areas, the prefrontal cortex, and the parietal cortex, there were differences in the topography and the relative strength of projections from these areas.

There were few common inputs to PMv and PMd; only the supplementary eye fields projected to all three areas studied. Interconnections within PMd or PMv appeared to link hindlimb and forelimb representations, and forelimb and face representations; however, connections between PMd and PMv were sparse. Areas cPMd and PMv were found to receive inputs from other motor areas—the primary motor area, the supplementary motor area, and the cingulate motor area—but the topography and strength of projections from these areas varied. Area rPMd was found to receive sparse inputs, if any, from these motor areas. The frontal eye field (area 8a) was found to project to PMv and rPMd, and area 46 was labeled substantially only from rPMd. Parietal projections to PMv were found to originate from a variety of somatosensory and visual areas, including the second somatosensory cortex and related areas in the parietal operculum of the lateral sulcus, as well as areas 5, 7a, and 7b, and the anterior intraparietal area. By contrast, projections to cPMd arose only from area 5. Visual areas 7m and the medial intraparietal area were labeled from rPMd. Relatively more parietal neurons were labeled after tracer injections in PMv than in PMd. Thus, PMv and PMd appear to be parts of separate, parallel networks for movement control.     

Horseradish peroxidase study of the associative connections of the motor region of the cerebral cortex in cats

Somatotopic organization of the body representation in the motor cortex of the cat's brain and a high degree of differentiation in the organization of associative projections between the motor and the somatosensory cortex was shown by means of retrograde transport of horse-radish peroxidase. Pyramid and stellate neurones of the second and the third cortical layers participate in the formation of these projections and interconnections.     

Three-dimensional electrophysiological topography of the rat corticostriatal system

Projections from the cerebral cortex are the major afferents of the caudoputamen and probably determine the functions subserved by each region of the nucleus. The corticostriatal system has been mapped using cytological techniques which give little information on the physiological importance of projections from individual cortical areas. The objective of this study was to characterize the three-dimensional topography of the corticostriatal system in the rat and to determine the physiological significance of these projections using electrophysiological techniques. Eight functionally distinct areas of the cerebral cortex (prefrontal, primary motor, rostral and caudal primary somatosensory, hindlimb, auditory, occipital and primary visual) were stimulated while recording the multiple unit activity in seven dorsal and seven ventral areas of the caudoputamen. Each stimulation site produced a distinctive pattern of activation within the caudoputamen. There was also a large site-dependent variation in electrophysiological activation produced by each stimulation. The motor and somatosensory areas produced the most powerful overall activation. In addition, a number of trends were obvious. There was a rostrocaudal topographical relationship between the site of stimulation and the area of the caudoputamen activated. Furthermore, more caudally and medially placed stimulation sites produced greater dorsal activation of the caudoputamen relative to ventral.     

Functional topography of afferent projections of the horizontal division of the nucleus of the diagonal band in the dorsolateral neocortex of the cat

EPs recording under Nembutal anaesthesia during stimulation of the medial section of the horizontal part of the diagonal band nucleus (HNDB) shows a wide spreading of HNDB afferentation over the neocortex: from the frontal area to the medial and some posterior parts of the auditory, parietal areas and Ep zone, with the least activation of the latter three regions and activation increasing intensity correspondingly in the somatic zones II, I (SII, SI), motor and frontal cortex. Such reduction of signals flow intensity oriented both in caudal and ventral directions of the cortex goes with foci of maximal activity of these signals in the motor, parietal areas and zones of representation of various body parts in SI and SII. Traits of similarity and differences of signal's projections in the neocortex from HNDB and thalamic relay nuclei have been revealed. A hypothesis is substantiated on different mechanisms underlying peculiarities of influences of these subcortical nuclei on the cortex depending on the type of their afferent-neuronal links in the latter and their functional role in the brain activity.     

Is the Outgrowth of Transplant-Derived Axons Guided by Host Astrocytes and Myelin Loss?

Loss of cortical neurons may lead to sever and sometimes irreversible deficits in motor function in a number of neuropathological conditions. Absence of spontaneous axonal regeneration following trauma in the adult central nervous system (CNS) is attributed to inhibitory factors associated to the CNS white matter and to the non-permissive environment provided by reactive astrocytes that form a physical and biochemical barrier scar. Neural transplantation of embryonic neurons has been widely assessed as a potential approach to overcome the generally limited capacity of the mature CNS to regenerate axons or to generate new neurons in response to cell loss. We have recently shown that embryonic (E14) mouse motor cortical tissue transplanted into the damaged motor cortex of adult mice developed efferent projections to appropriate cortical and subcortical host targets including distant areas such as the spinal cord, with a topographical organization similar to that of intact motor cortex. Several parameters might account for the outgrowth of axonal projections from embryonic neurons within a presumably non-permissive adult brain, among which are astroglial reactions and myelin formation. In the present study, we have examined the role of astrocytes and myelin in the axonal outgrowth of transplanted neurons.Key Words: motor cortex, neuronal transplantation, embryonic cells, GFP, GFAP, PLP     

Changes in amplitude and temporal characteristics of evoked potentials in the sensomotor cortex after division of the spinocervical tracts in cats

Temporal and amplitude characteristics of evoked potentials of the sensomotor cortex in waking cats were studied during variation in the intensity of electrodermal stimulation. The results obtained in experiments on intact animals and on the same animals for several months after division of the spinocervical tracts at the cervical level were compared. After blocking of the inflow of afferent impulses along these tracts of the spinal cord, statistically significant changes in evoked potentials were observed, mainly in response to medium and strong stimulation. These changes were more clear in the motor and second somatosensory areas of the cortex. A decrease in sensitivity to pain also was found. During recovery of the motor functions, cutaneous sensation remained impaired and the amplitude characteristics of the evoked somatosensory activity were not restored. The results suggest that thinner fibers predominate among the primary afferent fibers of the spinocervical tract, and their projections are more widely represented in the second somatosensory and motor areas of the cortex.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 516–523, September–October, 1972.     

Is the Outgrowth of Transplant-Derived Axons Guided by Host Astrocytes and Myelin Loss?

Loss of cortical neurons may lead to sever and sometimes irreversible deficits in motor function in a number of neuropathological conditions. Absence of spontaneous axonal regeneration following trauma in the adult central nervous system (CNS) is attributed to inhibitory factors associated to the CNS white matter and to the non-permissive environment provided by reactive astrocytes that form a physical and biochemical barrier scar. Neural transplantation of embryonic neurons has been widely assessed as a potential approach to overcome the generally limited capacity of the mature CNS to regenerate axons or to generate new neurons in response to cell loss. We have recently shown that embryonic (E14) mouse motor cortical tissue transplanted into the damaged motor cortex of adult mice developed efferent projections to appropriate cortical and subcortical host targets including distant areas such as the spinal cord, with a topographical organization similar to that of intact motor cortex. Several parameters might account for the outgrowth of axonal projections from embryonic neurons within a presumably non-permissive adult brain, among which are astroglial reactions and myelin formation. In the present study, we have examined the role of astrocytes and myelin in the axonal outgrowth of transplanted neurons.     

Laminar analysis of excitatory local circuits in vibrissal motor and sensory cortical areas

Rodents move their whiskers to locate and identify objects. Cortical areas involved in vibrissal somatosensation and sensorimotor integration include the vibrissal area of the primary motor cortex (vM1), primary somatosensory cortex (vS1; barrel cortex), and secondary somatosensory cortex (S2). We mapped local excitatory pathways in each area across all cortical layers using glutamate uncaging and laser scanning photostimulation. We analyzed these maps to derive laminar connectivity matrices describing the average strengths of pathways between individual neurons in different layers and between entire cortical layers. In vM1, the strongest projection was L2/3→L5. In vS1, strong projections were L2/3→L5 and L4→L3. L6 input and output were weak in both areas. In S2, L2/3→L5 exceeded the strength of the ascending L4→L3 projection, and local input to L6 was prominent. The most conserved pathways were L2/3→L5, and the most variable were L4→L2/3 and pathways involving L6. Local excitatory circuits in different cortical areas are organized around a prominent descending pathway from L2/3→L5, suggesting that sensory cortices are elaborations on a basic motor cortex-like plan.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

Effect of succinylcholine on responses of neurons in the motor cortex to natural activation of muscle spindle primary endings.

In locally anesthetized cats, the effects of intravenous administration of succinylcholine (SCh) in sub-paralytic dosages on the responses of single neurons in motor cortex to small dynamic muscle stretches were studied. A large transient enhancement of these cortical responses with a time course corresponding to the peripheral action of SCh on muscle spindles was observed. This finding is discussed in terms of the hypothesis that muscle spindle primary endings may activate projections to motor cortex.     

Forebrain projections to the hypothalamic locomotor region in cats

Descending projections from the cortex and basal ganglia to the hypothalamic locomotor region were studied in cats by the retrograde axonal transport of horse-radish peroxidase method. Neurons forming direct projections to the physiologically identified hypothalamic locomotor region are diffusely scattered over different gyri, but predominantly in areas 4 and 6 of the motor cortex, and also in the entopeduncular nucleus. Powerful cortico- and pallido-hypothalamic projections mainly do not reach as far as the most caudal zones of the hypothalamus, where the region whose electrical stimulation evokes locomotion lies.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 2, pp. 255–263, March–April, 1985.     

Comparison of the Connectional Properties of the Two Forelimb Areas of the Rat Sensorimotor Cortex: Support for the Presence of a Premotor or Supplementary Motor Cortical Area

The existence of multiple motor cortical areas that differ in some of their properties is well known in primates, but is less clear in the rat. The present study addressed this question from the point of view of connectional properties by comparing the afferent and efferent projections of the caudal forelimb area (CFA), considered to be the equivalent of the forelimb area of the primary motor cortex (MI), and a second forelimb motor representation, the rostral forelimb area (RFA). As a result of various tracing experiments (including double labeling), it was observed that CFA and RFA had reciprocal corticocortical connections characterized by preferential, asymmetrical, laminar distribution, indicating that RFA may occupy a different hierarchical level than CFA, according to criteria previously discussed in the visual cortex of primates. Furthermore, it was found that RFA, but not CFA, exhibited dense reciprocal connections with the insular cortex. With respect to their efferent projection to the basal ganglia, it was observed that CFA projected very densely to the lateral portion of the ipsilateral caudate putamen, whereas the contralateral projection was sparse and more restricted. The ipsilateral projection originating from RFA was slightly less dense than that from CFA, but it covered a larger portion of the caudate putamen (in the medial direction); the contralateral projection from RFA to the caudate putamen was of the same density and extent as the ipsilateral projection. The reciprocal thalamocortical and corticothalamic connections of RFA and CFA differed from each other in the sense that CFA was mainly interconnected with the ventrolateral thalamic nucleus, while RFA was mainly connected with the ventromedial thalamic nucleus. Altogether, these connectional differences, compared with the pattern of organization of the motor cortical areas in primates, suggest that RFA in the rat may well be an equivalent of the premotor or supplementary motor area. In contrast to the corticocortical, corticostriatal, and thalamocortical connections, RFA and CFA showed similar efferent projections to the subthalamic nucleus, substantia nigra, red nucleus, tectum, pontine nuclei, inferior olive, and spinal cord.     

Cortico-nigral projections in the cat

Using the methods of retrograde axonal transport of horseradish peroxidase and silver impregnation of degenerating axons, certain data have been obtained demonstrating that frontal, motor, orbital, insular and limbic fields of the cortex serve as sources of afferent fibers for the compact zone of the substantia nigra. The lateral zone gets projections from the same cortical areas (besides the limbic one) as the compact part and, in addition, from the parietal associative, acoustic and visual areas.     

Creating abstract topographic representations: Implications for coding,learning and reasoning

Topographic maps are a fundamental and ubiquitous feature of the sensory and motor regions of the brain. There is less evidence for the existence of conventional topographic maps in associational areas of the brain such as the prefrontal cortex and parietal cortex. The existence of topographically arranged anatomical projections is far more widespread and occurs in associational regions of the brain as well as sensory and motor regions: this points to a more widespread existence of topographically organised maps within associational cortex than currently recognised. Indeed, there is increasing evidence that abstract topographic representations may also occur in these regions. For example, a topographic mnemonic map of visual space has been described in the dorsolateral prefrontal cortex and topographically arranged visuospatial attentional signals have been described in parietal association cortex. This article explores how abstract representations might be extracted from sensory topographic representations and subsequently code abstract information. Finally a simple model is presented that shows how abstract topographic representations could be integrated with other information within the brain to solve problems or form abstract associations. The model uses correlative firing to detect associations between different types of stimuli. It is flexible because it can produce correlations between information represented in a topographic or non-topographic coordinate system. It is proposed that a similar process could be used in high-level cognitive operations such as learning and reasoning.     

Direct projections of the thalamic centrum medianum in the cerebral cortex of the cat (radioautographic studies)

After injection of radioactive amino acids into the cat thalamic centrum medianum, its projections have been revealed in the ipsilateral hemisphere in the frontal, motor, limbic, orbital and basal temporal cortex, in the parasubiculum and striatum. The anterograde tracing of the fibers and terminals reveals the centrum medianum projections in the layers VI-V and I of the frontal and limbic cortex and in the layers VI-V, IV or III (or in both) and in I of the motor and orbital cortex.     

Top-down control of motor cortex ensembles by dorsomedial prefrontal cortex

Dorsomedial prefrontal cortex is critical for the temporal control of behavior. Dorsomedial prefrontal cortex might alter neuronal activity in areas such as motor cortex to inhibit temporally inappropriate responses. We tested this hypothesis by recording from neuronal ensembles in rodent dorsomedial prefrontal cortex during a delayed-response task. One-third of dorsomedial prefrontal neurons were significantly modulated during the delay period. The activity of many of these neurons was predictive of premature responding. We then reversibly inactivated dorsomedial prefrontal cortex while recording ensemble activity in motor cortex. Inactivation of dorsomedial prefrontal cortex reduced delay-related firing, but not response-related firing, in motor cortex. Finally, we made simultaneous recordings in dorsomedial prefrontal cortex and motor cortex and found strong delay-related temporal correlations between neurons in the two cortical areas. These data suggest that functional interactions between dorsomedial prefrontal cortex and motor cortex might serve as a top-down control signal that inhibits inappropriate responding.     

The thalamus in the motor system.

The ventrolateral (VL) and anterior (VA) are the main thalamic relay for cerebellar and pallidal efferents going to the motor cortex. Four aspects of the function of these nuclei are briefly considered. (1) It is well known that these thalamic structures are not a simple relay on the way to the motor cortex, but that they have a gating function for the cerebellar afferents. The gating mechanism is active during slow-wave sleep, with deafferentation and with the use of various anesthetics. Possibly, it might play a role in the central organization of movement. (2) The organization at the unitary level of the projections between VL and motor cortex is examined and their role in the command of motor synergies through the motor cortex is strongly suggested. (3). It appears that unitary activity of VL neurons is not only related to movement but also to postural changes associated with movement. (4) The sensory input to VL nucleus is briefly analyzed. The inefficacy of exteroceptive stimulation in awake animals, in contrast with the effect of the same stimulation in anesthetized preparations, is discussed.     

Environmental enrichment modulates cortico-cortical interactions in the mouse

Environmental enrichment (EE) is an experimental protocol based on a complex sensorimotor stimulation that dramatically affects brain development. While it is widely believed that the effects of EE result from the unique combination of different sensory and motor stimuli, it is not known whether and how cortico-cortical interactions are shaped by EE. Since the primary visual cortex (V1) is one of the best characterized targets of EE, we looked for direct cortico-cortical projections impinging on V1, and we identified a direct monosynaptic connection between motor cortex and V1 in the mouse brain. To measure the interactions between these areas under standard and EE rearing conditions, we used simultaneous recordings of local field potentials (LFPs) in awake, freely moving animals. LFP signals were analyzed by using different methods of linear and nonlinear analysis of time series (cross-correlation, mutual information, phase synchronization). We found that EE decreases the level of coupling between the electrical activities of the two cortical regions with respect to the control group. From a functional point of view, our results indicate, for the first time, that an enhanced sensorimotor experience impacts on the brain by affecting the functional crosstalk between different cortical areas.     

The organization and connections of somatosensory cortex in the brush-tailed possum (Trichosurus vulpecula): evidence for multiple, topographically organized and interconnected representations in an Australian marsupial

Microelectrode mapping techniques were used to determine the organization of somatosensory cortex in the Australian brush-tailed possum (Trichosurus vulpecula). The results of electrophysiological mapping were combined with data on the cyto- and myeloarchitecture, and patterns of corticocortical connections, using sections cut tangential to the pial surface. We found evidence for three topographically organized representations of the body surface that were coextensive with architectonic subdivisions. A large, discontinuous cutaneous representation in anterior parietal cortex was termed the primary somatosensory area (SI). Lateral to SI we found evidence for two further areas, the second somatosensory area (SII) and the parietal ventral area (PV). While neurones in all of these areas were responsive to cutaneous stimulation, those of SI were non-habituating, whereas those in SII and PV often habituated to the stimuli. Moreover, neuronal receptive fields in SII and PV were, in general, larger than those in SI. Neurones in cortex adjacent to the rostral and caudal boundaries of SI, including cortex that interdigitated between the discontinuous SI head and body representations, required stimulation of deep receptors in the periphery to elicit responses. Within the region of cortex containing neurones responsive to stimulation of deep receptors, body parts were represented in a mediolateral progression. Injections of anatomical tracers placed in electrophysiologically identified locations in SI revealed ipsilateral connections with other parts of SI, as well as cortex rostral to, caudal to, and interdigitating between, SI. Injections in SI also resulted in labelling in PV, SII, motor cortex, posterior parietal cortex and perirhinal cortex. The patterns of contralateral projections reflected those of ipsilateral projections, although they were relatively less dense. The present findings support recent observations in other marsupials in which multiple representations of the body surface were described, and suggest that multiple interconnected sensory representations may be a common feature of cortical organization and function in marsupials.     

The hypocretin neuron system: an arousal system in the human brain

Hypocretins are recently discovered neuropeptides produced by a small group of posterior hypothalamic neurons which project widely over the neuroaxis. In this study, we note that hypocretin neuron perikarya in the human brain are localized to the perifornical region of the posterior hypothalamus, extending into the lateral hypothalamus. These neurons lightly innervate all areas of cerebral cortex studied in a variable pattern with denser innervation of association cortex than primary motor or sensory cortex. There is a dense innervation of hypothalamus, locus coeruleus, raphe nuclei, midline thalamus and nucleus of the diagonal band-nucleus basalis complex of the forebrain. This pattern of projections from the hypocretin neurons is compatible with an important role in arousal and the maintenance of the waking state.