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Modulation of somatosensory evoked responses in the primary somatosensory cortex produced by intracortical microstimulation of the motor cortex in the monkey.

Previous studies have shown that the amplitude of somatosensory evoked potentials is diminished prior to, and during, voluntary limb movement. The present study investigated the role of the motor cortex in mediating this movement-related modulation in three chronically prepared, awake monkeys by applying low intensity intracortical microstimulation (ICMS) to different sites within the area 4 representation of the arm. Air puff stimuli were applied to the contralateral arm or adjacent trunk at various delays following the ICMS. Somatosensory evoked potentials were recorded from the primary somatosensory cortex, areas 1 and 3b, with an intracortical microelectrode. The principal finding of this study was that very weak ICMS, itself producing at most a slight, localized, muscle twitch, produced a profound decrease in the magnitude of the short latency component of the somatosensory evoked potentials in the awake money. Higher intensities of ICMS (suprathreshold for eliciting electromyographic (EMG) activity in the "target" muscle, i.e. that muscle activated by area 4 stimulation) were more likely to decrease the evoked response and produced an even greater decrease. The modulation appeared to be, in part, central in origin since (i) it preceded the onset of EMG activity in 23% of experiments, (ii) direct stimulation of the muscle activated by ICMS, which mimicked the feedback associated with the small ICMS-induced twitch, was often ineffective and (iii) the modulation was observed in the absence of EMG activity. Peripheral feedback, however, may also make a contribution. The results also indicate that the efferent signals from the motor cortex can diminish responses in the somatosensory cortex evoked by cutaneous stimuli, in a manner related to the somatotopic order. The effects are organized so that the modulation is directed towards those neurones serving skin areas overlying, or distal to, the motor output.

Animals

Somatotopically organized transient projections from the primary somatosensory cortex to the cerebellar cortex.

The organization of transient projections from the primary somatosensory cortex (S-I) to the cerebellar cortex in neonatal kittens was examined using orthograde intraaxonal labeling techniques. Tritiated amino acid injections into face, forelimb and hindlimb areas of representation in S-I labeled mossy fiber-like terminals of cerebrocerebellar axons in different areas of the cerebellar cortex bilaterally. The hindlimb area of S-I projected to lobules I-IV in the anterior lobe and to ventral folia of the paramedian lobule (PML). Injections into forelimb areas of S-I labeled terminals in lobules IV and V and in intermediate and dorsal folia of the PML. The face area of S-I projected to the lobules V and VI, to medial folia in the ansiform and simplex lobules and to dorsal PML folia. Labeled terminals were more numerous in the cerebellar cortex contralateral to the S-I injections, except in lobules I and II and the ventral PML where the density of hindlimb input was approximately the same on both sides. These observations were supplemented by findings that small wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections into the dorsal or ventral PML resulted in retrogradely labeled layer V pyramidal neurons in lateral (face and forelimb) and medial (hindlimb) areas of S-I respectively. The somatotopic organization of transient S-I cerebrocerebellar projections is very similar to the topography of cerebellar somatosensory afferent pathways in adult cats.

Afferent Pathways

Organization of climbing fibre projections to the cerebellar cortex from trigeminal cutaneous afferents and from the SI face area of the cerebral cortex in the cat.

1. In cats anaesthetized with pentobarbitone, the projection of climbing fibres (CFs) to the cerebellar cortex from trigeminal cutaneous branches and from the face area of the sensorimotor (SI) cortex was mapped, using the technique of laminar field potential analysis. 2. The CF projections from both the trigeminal nerve and the SI face area were found to be localized to the same cerebellar folia, viz. chiefly the ipsilateral lobule HVI, with a small overlap on to the adjacent folia of lobule V and crus Ia of HVIIA. Frequently a projection from the superficial radial nerve to part or all of this area, was also found. 3. A correspondence in the distribution and amplitudes of CF potentials evoked at most points by stimulation of the trigeminal nerve and the SI cortex was found. This implies a convergence of afferents from these two sources at or before the inferior olive. 4. In more than half of the cats, a small area of the cerebellar hemisphere was found, in which contralateral as well as ipsilateral trigeminal stimulation would evoke CF potentials. Usually inputs from the superficial radial nerve and the SI cortex also converged upon this area. 5. The organization of CF projections from trigeminal and superficial radial nerve afferents to the cerebellar hemisphere was found to occur in the same 'patchy' pattern of somatotopy that has been described for spinal nerve inputs to the anterior lobe. 6. One constant factor was found in the pattern of organization of CF projections to this area from cutaneous afferent nerves. That is, only the afferents from overlapping areas of skin projected to a given recording point: no instance of CF projections from trigeminal branches innervating discontinuous skin areas was observed.

Animals

Functional properties of single neurons in the face primary motor cortex of the primate. I. Input and output features of tongue 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)

Animals

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. II. VIP-, somatostatin-, and NPY-immunoreactive neurons.

Fetal frontal cortex transplants that survived 2-9 months in cavities in adult rat motor/sensory cortex were processed for vasoactive intestinal polypeptide (VIP), somatostatin 14 (SS), and neuropeptide Y (NPY) immunocytochemistry, and NADPH-diaphorase (NADPH-d) histochemistry. All transplants had surviving VIP, SS, NPY, and NADPH-d neuronal perikarya and fibers with normal adult morphology. The number of peptidergic neurons within transplants, however, often appeared to be less than that in equivalent areas of host cortex. Most transplanted SS and VIP neuronal perikarya did not migrate to form the laminae characteristic of normal cortex. A few transplants had SS and VIP cells arranged in laminae in which the VIP processes were parallel to one another and perpendicular to one transplant surface, approximating normal host neocortex. VIP, NPY, and SS fibers crossed between host brains and transplants, suggesting that peptide host-transplant interactions are possible. All adult host cortical and most transplanted NPY neurons colocalized with NADPH-d. The failure of some transplanted NPY neurons to express NADPH-d suggests these transplanted cells may be functionally impaired, but that they can survive without the NADPH-d enzyme.

Animals

Somatosensory cortex of the neonatal pig: I. Topographic organization of the primary somatosensory cortex (SI).

The cerebral cortex of adult mammals contains several somatotopic representations of the body surface. Although the organization of the various somatosensory cortices of numerous species of adult animals has been elucidated, data on the somatosensory representations of fetal and neonatal animals are limited. As part of an investigation into the perinatal development of the somatosensory cortices, it was necessary to delineate the organization of the somatosensory cortices of the perinatal pig. This study presents the topographical organization of the primary somatosensory cortex (SI) of the perinatal pig. Multiunit microelectrode mapping methods were used to produce topographic maps of SI from barbiturate anesthetized pigs ranging in age from 7 days preterm to 2 months postpartum. It was demonstrated that the overall organization of this region of cortex was similar to that of other mammals: a somatotopic projection of predominantly the contralateral body surface was delineated in which the hindlimb is represented medially and the face laterally across the cortex. A disproportionately enlarged rostrum representation was mapped in detail, and multiple representations of the rostrum, face, and mouth were found. Several of these representations exhibited bilateral and ipsilateral input. The SI trunk and hindlimb representations were located on the medial wall of the hemisphere; these representations were small but their presence refutes speculation that ungulates do not have a complete body representation in SI.

Animals

Effects of THA on passive avoidance retention performance of intact, nucleus basalis, frontal cortex and nucleus basalis + frontal cortex-lesioned rats.

Unilateral quisqualic acid lesions of the nucleus basalis magnocellularis (NBM) produced marked choline acetyltransferase depletion (-67% ipsilateral to lesion) and impaired passive avoidance (PA) retention at 24 hours. Pretraining injections of tacrine (THA: 1, 3 and 5 mg/kg), an anticholinesterase, failed to facilitate PA retention in intact rats. However, the retention performance of NBM-lesioned rats was improved by pretraining administration of THA at 3 mg/kg but not at either 1 or 5 mg/kg. Frontal cortex lesioning did not impair PA retention, and THA at 3 mg/kg had no effect on the PA retention of frontal cortex-lesioned rats. THA at 3 mg/kg failed to improve retention performance of NBM + frontal cortex-lesioned rats. After 10 days of chronic treatment with THA, NBM lesion-induced PA retention deficits were partially restored at both 3- and 5-mg/kg doses. The results suggest that 1) the insult to cholinergic neurons in the NBM may be involved in the PA memory consolidation deficit induced by nonselective quisqualic acid lesioning; 2) the beneficial effects of THA on NBM lesion-induced PA retention deficit occur in a narrow dose range; 3) the alleviating effects of THA on NBM lesion-induced PA memory deficits are blocked by frontal cortex lesions; and 4) the dose-response window for THA-induced PA retention performance improvement is broadened by repeated treatment.

Animals

Antibody labeling of functional subdivisions in visual cortex: Cat-301 immunoreactivity in striate and extrastriate cortex of the macaque monkey.

We have examined the distribution of immunoreactivity for the monoclonal antibody Cat-301 in visual cortex of the macaque monkey. Remarkably, those portions of striate cortex (V1) and extrastriate cortex that are most immunoreactive for Cat-301 are anatomically interconnected and are dominated by inputs arising from the magnocellular layers of the LGN (which are themselves highly immunoreactive). In particular, we found that a band of Cat-301 labeled neurons known to exist in layer 4 of V1 is centered on the boundary between layers 4C alpha and 4B and thus includes portions of both the primary target of the magnocellular LGN and its subsequent relay through layer 4B. We also demonstrated consistently strong Cat-301 immunoreactivity in all three extrastriate targets of layer 4B: areas V3, MT, and the cytochrome-oxidase (CO) enriched thick stripes of V2. In V2, there was a close correlation between Cat-301 labeling and clusters of cells projecting to MT but not to V4. This was true even in regions where the CO pattern was equivocal or irregular, indicating that Cat-301 is a more reliable marker than CO for the thick-stripe subregions of V2. Finally, we found strong Cat-301 immunoreactivity in at least parts of areas V3A, the MST complex, and the posterior parietal complex, but not in area V4 or inferotemporal cortex. The molecular specificity revealed by this single marker thus correlates with functionally specific subdivisions at each hierarchical level over nearly the entire known extent of the visual pathway in macaques. This supports the notion that these subdivisions form an anatomically, physiologically, and now molecularly distinct pathway known as the M-stream.

Animals

Cotransplantation of embryonic mouse retina with tectum, diencephalon, or cortex to neonatal rat cortex.

Retinae from embryonic mice were transplanted to the occipital cortex of neonatal rats together with their normal target regions, tectum or diencephalon, from embryonic mice or rats. In control experiments, retinae were cotransplanted with embryonic rat occipital cortex. In over 80% of the experimental animals, both transplants differentiated and grew. Ganglion cells in the retinae cotransplanted close to tectum or diencephalon survived for at least 15 weeks. Their survival was associated with the development of a distinct optic fiber layer and outgrowth of axons from the transplanted mouse retina. Specific innervation of distinct patches within the cotransplanted rat tectum or diencephalon was demonstrated by the use of an anti-mouse antibody. The innervated regions, which could be as far away as 1.3 mm from the retinae, were correlated with cytological features of the cotransplanted tectum or diencephalon. By contrast, the host cortex was never innervated by the transplanted retinae. In the control animals in which the retinae were cotransplanted with occipital cortex and in four animals in which the cotransplants lay more than 2.7 mm apart, no ganglion cells were identified and there was no evidence of an optic fiber layer, outgrowth of axons, or innervation. These results support the idea that in order to survive, retinal ganglion cells need to innervate an appropriate target region. Further, the specific innervation of regions within the cotransplanted tectum or diencephalon suggests that these target regions are able to exert a tropic influence on the axons of retinal ganglion cells, even in the absence of many of the normal structure cues.

Animals

Relation of olfactory bulb and cortex. II. Model for driving of cortex by bulb.

The major projection pathway of the olfactory bulb is by way of the lateral olfactory tract (LOT) to the olfactory cortex. Oscillatory bursts of extracellular potential appear during inspiration in both bulb and cortex. Based on anatomical and physiological considerations, a model was proposed, consisting of a bulbar transmitter, a conduction line representing axons in the LOT, and a cortical receiver. The model predicted the relation between phase and frequency of bulbar and cortical burst pairs, based on the expectation that the bulb drives the cortex. Experimental phase-frequency plots were computed from bursts of 9 bulbocortical electrode site pairs from each of 10 rabbits. For each site pair, the model predicted the expected range of the joint variation of phase and frequency, using the known distance between the bulbar and cortical sites. The model was highly successful (greater than 95% prediction accuracy) for one quarter of the total number of site pairs examined. The wide range of variation for the rest of the data suggested that higher order interactions are responsible for the phase relation between bulb and cortex. Convergence of input, independence of the cortical generator, cortical feedback to the bulb and synchronization by an outside source are all discussed as possible contributors to this variation.

Animals

Intraventricular administration of the cholinotoxin AF64A increases the accumulation of aluminum in the rat parietal cortex and hippocampus, but not in the frontal cortex.

Aluminum (Al) concentrations of the rat frontal cortex, parietal cortex, and hippocampus were measured by atomic absorption spectroscopy 16 days after a unilateral intracerebroventricular injection of Na gluconate, Al gluconate, or the cholinotoxin AF64A. A fourth group of rats were injected with AF64A 6 days before injection of Al gluconate and subsequently sacrificed 10 days later. The combined treatment of AF64A and Al gluconate resulted in enhanced intraneuronal accumulation of Al in the parietal cortex and hippocampus but not in the frontal cortex. Consequently, Al may not be considered to be a primary factor in the pathogenesis of Alzheimer's disease.

Aluminum

Electrophysiological influences of the parietal cortex and dorso-medial thalamic nucleus on the prefrontal cortex of the cat.

Lesion studies have shown that the functional integrity of prefrontal and posterior parietal cortex is necessary for complex behavioural performance. Recordings were made from 137 prefrontal cells in awake cats. Parietal cortex stimulation affected fifty-four cells (39.5%); thirty-four (63%) increased and twenty (37%) decreased their discharge frequency. Thalamic stimulation affected forty-seven cells; twenty-eight increased their discharge and nineteen decreased it. These responses suggest firstly that the organization between parietal and prefrontal cortex is similar to that in monkeys, and secondly that prefrontal cortex has an integrative role.

Animals

Long-lasting potentiation of synaptic potentials in the motor cortex produced by stimulation of the sensory cortex in the cat: a basis of motor learning.

A long-lasting increase in the efficiency of synaptic transmission in the central nervous system has been thought to be one of the bases of learning and memory. To explore the possibility that the motor cortex (area 4 gamma) itself is involved in motor learning, the existence of long-term potentiation (LTP) was examined by recording excitatory postsynaptic potentials (EPSPs) from motor cortical neurons. Short tetanic intracortical microstimulation (ICMS) of the somatic sensory cortex produced a marked potentiation of the EPSPs in a small group of motor cortical neurons. The results raised the possibility that the input from the sensory cortex participates in motor learning and retention of the learned motor skills.

Animals

Effects of early environments on monkey cortex neuroanatomical changes following somatomotor experience: effects on layer III pyramidal cells in monkey cortex.

Sixteen infant stumptail monkeys were reared to 6 months under four conditions. Behaviors and cortical neuroanatomy were compared. Earlier studies showed effects on stellate cell dendrites. Here are reported the results in six cortical areas on basilar dendrites of layer III pyramidal cells. Basilar dendrites show significantly larger numbers (p less than .05) of branching for motor I cortex under condition 3 associated with the greatest skills and amount of activity in climbing, swinging, and grasping of objects. Visual cortex was not significantly altered by the rearing conditions, but the basilar dendrites showed less branching than in the five other areas of cortex sampled. It is concluded that genetic factors are responsible for the major growth patterns and that environmental factors contribute to quantitative increases or decreases in the branching of dendrites and therefore the finer tuning of neural interconnections.

Animals

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. I. NADPH-diaphorase neurons.

Fetal frontal cortex from 18-d-old embryonic rat brain was transplanted into cavities of juvenile host motor/sensory cortex. Two to seven months later, sections were reacted for NADPH-diaphorase (NADPH-d) enzyme histochemistry. NADPH-d-positive neurons survived in 11 of 13 grafts. All but one of the transplants had reduced numbers of these neurons, although in 3 transplants the reductions were moderate and not statistically significant. The distribution and morphology of NADPH-d neurons within most grafts was comparable to that of NADPH-d neurons in normal host cortex. At the margin of the 2 transplants with no NADPH-d neuronal perikarya, NADPH-d fibers crossed from host to transplant as far as a millimeter into the transplant, and on rare occasions, the host neurons that gave rise to these fibers were identified. This suggests that host-transplant interactions are possible. One transplant had an abnormally large number of NADPH-d-positive neurons and fibers, possibly due to selective survival of these neurons. The data reported here for NADPH-d in cortical transplants may also apply to neuropeptide Y (NPY), since nearly all neocortical NPY neurons also contain NADPH-d.

Animals

Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex.

We studied the visual responses of single neurons in three extra-striate visual areas of the macaque following lesions of striate cortex, lesions of the tecto-pulvinar system or both. After striate lesions, there was (a) considerable specific activity remaining in area MT including direction selectivity, (b) only non-specific activity in the superior temporal polysensory area (STP), and (c) no visual responsiveness at all in inferior temporal cortex (IT). In animals with striate lesions, interruption of the tecto-pulvinar pathway eliminated the residual visual activity in MT and STP that survived the striate lesions. Interruption of the tecto-pulvinar pathway alone had little or no effect on visual evoked activity in any of the three areas. These results are related to the relative dependence of visual responsiveness in MT, STP and IT on striate cortex and the superior colliculus, to differences between the dorsal and ventral cortical processing streams, and to neural mechanisms underlying blind sight.

Animals

Loss of hybridizable ribosomal DNA from human post-mitotic tissues during aging: II. Age-dependent loss in human cerebral cortex--hippocampal and somatosensory cortex comparison.

DNA was isolated from the hippocampal and from the somatosensory cortex of 13 humans (at autopsy). In both the cortex and hippocampus, the loss of ribosomal DNA (rDNA), as measured through hybridization in the liquid phase, approximates about 0.9% per year. The r value for somatosensory cortex was about -0.7 and that for the hippocampus was about -0.91. The correlation coefficient between the sets of two samples derived from the same individual (two different areas) in +0.945. These results are consistent with those reported concurrently for human myocardium and with earlier studies conducted with beagle dogs, in which only post-mitotic tissues (brain, heart and skeletal muscle) showed measurable decrements in these key genes. To the degree that the synthesis of new proteins is essential for sustained mental activity, these results are consistent with the observations that Nissl substance is more slowly replenished, following exhaustive work by motor cortical cells, and the fact that many older persons experience mental fatigue during continuous mental work at earlier times than do younger persons. The mechanism of loss is not certain, but may well be related to inadequacies in DNA repair systems, thereby allowing deletion of tandemly duplicated genes through cross-over "episome" formation, followed by degradation of the excised DNA segments. The ratio of loss of rDNA hybridizability in human and dogs in about 1 to 7, which approximates the relative ratios of their lifespans (reciprocals).

Adolescent

Dopaminergic innervation of the primary visual cortex in the rat, and some correlations with human cortex.

Dopaminergic terminals have been identified in the primary visual cortex with three techniques; immunocytochemistry with an anti-dopamine antiserum, retrograde axonal transport techniques using unconjugated wheat germ agglutinin and HPLC determination of catecholamines and metabolites in microdissected sub-regions of occipital cortex in the rat. The results demonstrate a specific dopaminergic innervation, arising from the ventral tegmental area, which is found mainly in laminae VI and V, but with minor innervation also in lamina I. Dopaminergic innervation to adjacent cortical regions is also described. Neurochemical data from post-mortem human material suggests that a similar innervation exists in man. An analysis of the distribution of dopaminergic fibres in relation to the known connections and possible functions of the deep laminae of visual cortex suggests that dopaminergic axons may participate in the corticofugal control of visual afferent pathways.

Aged