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.     

l-Dopa methyl ester attenuates amblyopia-induced neuronal injury in visual cortex of amblyopic cat

In the present study, we aimed to assess the potential anti-amblyopic effects of l-dopa methyl ester (LDME) on visual cortex area 17 in an amblyopic feline model induced by monocular vision deprivation. After LDME administration, pathophysiologic and ultrastructural observations were utilized to examine the morphological changes of nerve cells in visual cortex area 17. Dopamine (DA) and its metabolite contents in visual cortex area 17 were investigated through HPLC analysis. Apoptotic cells in visual cortex area 17 were evaluated by TUNEL assay. Additionally, the c-fos expression both at gene and protein levels was assessed using RT-PCR and immunohistochemistry analyses, respectively. The contents of DA and its metabolites were elevated in visual cortex area 17. Neuronal rejuvenation which occurred in visual cortex area 17 was observed through anatomical and physiological assessments. Similarly, TUNEL results showed that neuronal apoptosis was inhibited in the visual cortex of amblyopic cats by both l-dopa and LDME therapies. Meanwhile, the c-fos expression was notably up-regulated at both the mRNA and protein levels by the treatments. These findings suggested that LDME treatment could effectively increase DA and its metabolite contents, and restrain the apoptotic process, as well as elevate the c-fos expression in nerve cells of visual cortex area 17. Taken together, LDME might ameliorate the functional cytoarchitecture in visual cortex area 17 through mechanisms that elevate DA content and increase endogenous c-fos expression, as well as inhibit neuronal lesion in visual cortex tissue.     

Interactions of Phencyclidine Receptor Agonist MK-801 with Dopaminergic System: Regional Studies in the Rat

Interactions of the potent phencyclidine receptor agonist MK-801 with the dopaminergic system were examined in various brain regions in the rat. MK-801 increased dopamine (DA) metabolism in the pyriform cortex, entorhinal cortex, prefrontal cortex, striatum, olfactory tubercle, amygdala, and septum without affecting DA metabolism in the cingulate cortex and nucleus accumbens. In pyriform cortex and amygdala, MK-801 was more potent than phencyclidine at increasing DA metabolism. Local injections of MK-801 into ventral tegmental area and into the amygdala/pyriform cortex interface indicated that MK-801 may act at the cell body as well as the nerve terminal level to increase DA metabolism and that ongoing dopaminergic neuronal activity is a prerequisite for full drug action.     

Neuronal mechanisms of interaction of Deiters nucleus with the cerebral cortex.

The effects of stimulation of the vestibular nerve and five different cerebral cortex areas on the neuronal activity of the lateral vestibular nucleus of Deiters were studied. Stimulation of the cerebral cortex is shown to lead to antidromic and synaptic activation of Deiters neurons. The synaptic potentials of Deiters neurons evoked from the cerebral cortex were of mono- and polysynaptic origin. In particular, stimulation of the cerebral cortex evoked in Deiters neurons mono- and polysynaptic excitatory postsynaptic potentials. Collaterals of vestibulospinal neurons reaching different cortex fields as well as convergence of influences from these cortex fields on Deiters neurons were revealed. Inhibitory effects of the cerebral cortex on Deiters neurons were of polysynaptic origin and occurred rarely. The topical correlation between Deiters nucleus and different areas of the cerebral cortex was found. The peculiarities and functional significance of the effects obtained are discussed.     

Morphometric and histological studies on the adrenal glands of the camel Camelus dromedarius

The adrenal gland of the camel consists of an outer cortex and an inner medulla. The general disposition of the cortex and medulla, however, differs occasionally from that of other mammals. Extensions of medulla could reach as far as the periphery of the cortex. Islet of medullary tissue may be found in sections of the cortex and cortical tissue consisting of all zones of the cortex may occur around arteries or nerves in the medulla. The medulla may be separated from the cortex by connective tissue especially in old camels. The arrangement of noradrenaline-secreting cells is different from that in other ruminants; they are found in groups scattered between the adrenaline-secreting cells. Bundles of smooth muscle occur in venules at the corticomedullary interface. Accessory adrenal glands are found embedded in the renal fat. They are similar in structure to the adrenal gland. The adrenal cortex forms 74% of the volume of the gland and the ratio of the cortex to medulla is 4:1. The zona glomerulosa, fasciculata and reticularis constitute about 13%, 53%, and 29% by volume of the cortex, respectively.     

Frontal lobe and cognitive development

In phylogeny as in ontogeny, the association cortex of the frontal lobe, also known as the prefrontal cortex, is a late-developing region of the neocortex. It is also one of the cortical regions to undergo the greatest expansion in the course of both evolution and individual maturation. In the human adult, the prefrontal cortex constitutes as much as nearly one-third of the totality of the neocortex. The protracted, relatively large, development of the prefrontal cortex is manifest in gross morphology as well as fine structure. In the developing individual, its late maturation is made most apparent by the late myelination of its axonal connections. This and other indices of morphological development of the prefrontal cortex correlate with the development of cognitive functions that neuropsychological studies in animals and humans have ascribed to this cortex. In broad outline, the ventromedial areas of the prefrontal cortex, which with respect to otherprefrontal areas develop relatively early, are involved in the expression and control of emotional and instinctual behaviors. On the other hand, the late maturing areas of the lateral prefrontal convexity are principally involved in higher executive functions. The most general executive function of the lateral prefrontal cortex is the temporal organization of goal-directed actions in the domains of behavior, cognition, and language. In all three domains, that global function is supported by a fundamental role of the lateral prefrontal cortex in temporal integration, that is, the integration of temporally discontinuous percepts and neural inputs into coherent structures of action. Temporal integration is in turn served by at least three cognitive functions of somewhat different prefrontal topography: working memory, preparatory set, and inhibitory control. These functions engage the prefrontal cortex in interactive cooperation with other neocortical regions. The development of language epitomizes the development of temporal integrative cognitive functions and their underlying neural substrate, notably the lateral prefrontal cortex and other late-developing cortical regions.     

Angiotensin converting enzyme predominates in the inner cortex and medulla of the rat kidney

Regional distribution of angiotensin converting enzyme(ACE) in the rat kidney was studied. The ACE activities in the inner cortex and outer medulla were about 10 and 5 times those in the outer cortex, respectively. The activity in the inner medulla or papilla was much the same as that in the outer cortex. Immunofluorescence was greatest in the proximal tubules in the inner cortex, while the outer medulla and the inner medulla or papilla showed a weak fluorescence. The brush border membranes isolated from the inner cortex also possessed about 10 times the ACE activity seen in the outer cortex. The results indicate that the major source of renal ACE is not the proximal convoluted tubules in the outer cortex, but rather the brush border membranes of proximal tubules in the inner cortex. The contribution of ACE in the inner cortex would therefore be predominant.     

Functional architecture of auditory cortex

Three complementary approaches demonstrate new types of organization in rodent, feline and primate auditory cortex, as well as differences in processing between auditory and visual cortex. First, connectional work reveals patterns of thalamocortical and corticocortical input unique to the auditory cortex. Second, physiological studies find multiple, interleaved auditory processing modules related to corticocortical connections and embedded in the isofrequency gradient. Third, functional analyses demonstrate independent processing streams for sound localization and identification analogous to the 'what' and 'where' streams in visual cortex, although the modular arrangements are modality-specific. Taken together, these data show that the auditory cortex has common and unique functional substrates.     

Against memory systems

The medial temporal lobe is indispensable for normal memory processing in both human and non-human primates, as is shown by the fact that large lesions in it produce a severe impairment in the acquisition of new memories. The widely accepted inference from this observation is that the medial temporal cortex, including the hippocampal, entorhinal and perirhinal cortex, contains a memory system or multiple memory systems, which are specialized for the acquisition and storage of memories. Nevertheless, there are some strong arguments against this idea: medial temporal lesions produce amnesia by disconnecting the entire temporal cortex from neuromodulatory afferents arising in the brainstem and basal forebrain, not by removing cortex; the temporal cortex is essential for perception as well as for memory; and response properties of temporal cortical neurons make it impossible that some kinds of memory trace could be stored in the temporal lobe. All cortex is plastic, and it is possible that the same rules of plasticity apply to all cortical areas; therefore, memory traces are stored in widespread cortical areas rather than in a specialized memory system restricted to the temporal lobe. Among these areas, the prefrontal cortex has an important role in learning and memory, but is best understood as an area with no specialization of function.     

Central Nervous System Involvement in the Animal Model of Myodystrophy

Congenital muscular dystrophies present mutated gene in the LARGE mice model and it is characterized by an abnormal glycosylation of α-dystroglycan (α-DG), strongly implicated as having a causative role in the development of central nervous system abnormalities such as cognitive impairment seen in patients. However, the pathophysiology of the brain involvement remains unclear. Therefore, the objective of this study is to evaluate the oxidative damage and energetic metabolism in the brain tissue as well as cognitive involvement in the LARGE^(myd) mice model of muscular dystrophy. With this aim, we used adult homozygous, heterozygous, and wild-type mice that were divided into two groups: behavior and biochemical analyses. In summary, it was observed that homozygous mice presented impairment to the habituation and avoidance memory tasks; low levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex, hippocampus, cortex and cerebellum; increased lipid peroxidation in the prefrontal cortex, hippocampus, striatum, and cerebellum; an increase of protein peroxidation in the prefrontal cortex, hippocampus, striatum, cerebellum, and cortex; a decrease of complex I activity in the prefrontal cortex and cerebellum; a decrease of complex II activity in the prefrontal cortex and cerebellum; a decrease of complex IV activity in the prefrontal cortex and cerebellum; an increase in the cortex; and an increase of creatine kinase activity in the striatum and cerebellum. This study shows the first evidence that abnormal glycosylation of α-DG may be affecting BDNF levels, oxidative particles, and energetic metabolism thus contributing to the memory storage and restoring process.     

FREE AMINO ACIDS AND RELATED COMPOUNDS IN BIOPSIES OF HUMAN BRAIN

Abstract— Contents (μmol/g wet wt.) of 35 free amino acids and related compounds were measured in biopsies of human brain from ten patients. Brain specimens were frozen in liquid nitrogen within 10 sec of their removal at neurosurgery; thus, the values found should approximate those which occur in living brain.
Levels in free pools of biopsied cerebral cortex of most of the amino acids that are constituents of proteins were only 20-50 per cent of those found in autopsied cortex. The content of cystine and ethanolamine was much lower in biopsied than in autopsied cortex. Concentrations of GABA in biopsied cortex were only 20 per cent as high as those found in autopsied cortex, and levels of γ-aminobutyryl dipeptides were also significantly lower in biopsied cortex. Amounts of cystathionine in biopsied cortex varied markedly, but averaged much higher than in autopsied cortex; a single biopsy specimen of cerebellar grey matter had a cystathionine content 36-fold greater than the mean found in autopsied cerebellum.
Appreciable variability in contents among cortical biopsies was found for glycerophosphoethanolamine, phosphoethanolamine, ethanolamine, taurine, aspartic acid, glutamic acid, glutamine, and GABA, as well as for cystathionine. Whether this variability occurred between different subjects, or between different cortical areas, was not clear, although the former possibility was suggested by findings in multiple cortical biopsies from one patient.     

Illusory sensation of movement induced by repetitive transcranial magnetic stimulation

Human movement sense relies on both somatosensory feedback and on knowledge of the motor commands used to produce the movement. We have induced a movement illusion using repetitive transcranial magnetic stimulation over primary motor cortex and dorsal premotor cortex in the absence of limb movement and its associated somatosensory feedback. Afferent and efferent neural signalling was abolished in the arm with ischemic nerve block, and in the leg with spinal nerve block. Movement sensation was assessed following trains of high-frequency repetitive transcranial magnetic stimulation applied over primary motor cortex, dorsal premotor cortex, and a control area (posterior parietal cortex). Magnetic stimulation over primary motor cortex and dorsal premotor cortex produced a movement sensation that was significantly greater than stimulation over the control region. Movement sensation after dorsal premotor cortex stimulation was less affected by sensory and motor deprivation than was primary motor cortex stimulation. We propose that repetitive transcranial magnetic stimulation over dorsal premotor cortex produces a corollary discharge that is perceived as movement.     

Abnormalities of retinal metabolism in diabetes or experimental galactosemia. VI. Comparison of retinal and cerebral cortex metabolism,and effects of antioxidant therapy

Metabolic abnormalities observed in retina and in cerebral cortex were compared in diabetic rats and experimentally galactosemic rats. Diabetes or experimental galactosemia of 2 months duration significantly increased oxidative stress in retina, as shown by elevation of retinal thiobarbituric acid reactive substances (TBARS) and subnormal activities of antioxidant defense enzymes, but had no such effect in the cerebral cortex. Activities of sodium potassium adenosine triphosphatase [(Na,K)-ATPase] and calcium ATPase became subnormal in retina as well as in cerebral cortex. In contrast, protein kinase C (PKC) activity was elevated in retina but not in cerebral cortex in the same hyperglycemic rats. Dietary supplementation with an antioxidant mixture (containing ascorbic acid, Trolox, α-tocopherol acetate, N-acetyl cysteine, β-carotene, and selenium) prevented the diabetes- induced and galactosemia-induced elevation of retinal oxidative stress, the elevation of retinal PKC activity and the decrease of retinal ATPases. In cerebral cortex, administration of the antioxidant diet also prevented the diabetes-induced decreases in (Na,K)-ATPase and calcium ATPases, but had no effect on TBARS and activities of PKC and antioxidant-defense enzymes. The results indicate that retina and cerebral cortex differ distinctly in their response to elevation of tissue hexose, and that cerebral cortex is more resistant than retina to diabetes-induced oxidative stress. The greater resistance to oxidative stress in cerebral cortex, as compared to retina, is consistent with the resistance of cerebral cortex to microvascular disease in diabetes, and with a hypothesis that oxidative stress contributes to microvascular disease in diabetes. Dietary supplementation with these antioxidants offers a means to inhibit multiple hyperglycemia-induced retinal metabolic abnormalities.     

Structural rearrangements of the cerebral cortex in children and adolescents

The cortical formations of the brain involved in visual functions (the occipital and temporo-parieto- occipital areas, the oculomotor area of the prefrontal cortex), as well as the motor cortex in the representation zone of the arm and the medial region of the frontal cortex adjacent to the limbic lobe, were studied in post-mortem material. The thickness of the cortex and cortical layer III, the sizes of pyramidal neurons, the specific volumes of neurons and intracortical vessels were studied in subjects of both sexes, from birth to the age of 20 years, at yearly intervals (103 observations) using histological techniques, computer morphometric and stereological analysis. The thickness of the cortex of the cerebral hemispheres was observed to intensively increase from birth to the age of 3 years in the occipital, temporo-parieto-occipital and prefrontal cortical areas involved in visual recognition processes. The increase in thickness of the cerebral cortex continues until the age of 6 in the occipital cortex and in the oculomotor area, until the age of 7 years in the temporo-parietooccipital area and the medial prefrontal area, and until the age of 8–9 years in the motor cortex. The sizes of pyramidal neurons increase until the age of 6 years in the motor cortex, until the age of 8 years on the medial surface of the frontal lobe, and until the age of 9–10 years in the temporo-parieto-occipital area and in the dorsolateral area of the prefrontal cortex. The specific volume of neurons and blood vessels in the cortex of the cerebral hemispheres decreases and the volume of intracortical fibers increases throughout the ascending ontogeny, which is manifested most intensively in the prefrontal cortex.     

Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids,superoxide dismutase,and glutathione peroxidase activity

The whole brain free fatty acid (FFA) level, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined in the frontal cortex, cerebellum, hippocampus, and pons-medulla region of the single pentylenetetrazol (PZT)-treated and PZT-kindled Hannover-Wistar rats. PZT administration in the convulsive dose caused significant increase of the brain FFA content. Decreased SOD activity was detected in the frontal cortex of PZT-kindled rats, whereas decreased GPX activity was found in the frontal cortex and cerebellum of all treated rats, as well as in the hippocampus and pons-medulla of PZT-kindled rats. Kindling caused distinctive change of antioxidative defense in the frontal cortex, hippocampus, and pons-medulla region.     

Dynamic Changes in Brain Activations and Functional Connectivity during Affectively Different Tactile Stimuli

In the present study, we compared brain activations produced by pleasant, neutral and unpleasant touch, to the anterior lateral surface of lower leg of human subjects. It was found that several brain regions, including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII), as well as contralateral middle and posterior insula cortex were commonly activated under the three touch conditions. In addition, pleasant and unpleasant touch conditions shared a few brain regions including the contralateral posterior parietal cortex (PPC) and bilateral premotor cortex (PMC). Unpleasant touch specifically activated a set of pain-related brain regions such as contralateral supplementary motor area (SMA) and dorsal parts of bilateral anterior cingulated cortex, etc. Brain regions specifically activated by pleasant touch comprised bilateral lateral orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), intraparietal cortex and left dorsal lateral prefrontal cortex (DLPFC). Using a novel functional connectivity model based on graph theory, we showed that a series of brain regions related to affectively different touch had significant functional connectivity during the resting state. Furthermore, it was found that such a network can be modulated between affectively different touch conditions.     

Evoked impulse activity in neuronally isolated cortex

The reactions of neurons of the isolated cortex of one hemisphere to direct cortical stimulation were investigated in cats under Nembutal anesthesia. Isolation of the cortex was carried out by Khananashvili's method [10]. It is shown that phasic reactions develop in the isolated cortex in response to such stimulation: initial discharge, initial pause, first after-discharge, first after-pause, late after-discharges and pauses, as well as reactions of presumably inhibitory neurons. A majority of the cells (85%) which manifest background activity respond to direct electrical stimulation, and the frequency of the late after-reactions is twice as great as in the intact cortex. It is concluded that cortical elements of the isolated cortex retain their principal neurophysiological properties.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 3, No. 3, pp. 236–244, May–June, 1971.     

Regional variations in spontaneous unit activity in the neuronally isolated cortex

Unit activity of the visual, auditory, and association areas of the neuronally isolated cortex of one hemisphere was studied in acute experiments on cats (the method was described previously [5]). A few hours after operation, the same types of spontaneous unit activity are observed in the isolated cortex as in the intact cortex under identical experimental conditions. Unlike in the normal cortex, most cells in the neuronally isolated cortex discharge regularly. Spontaneously active cells are two or three times fewer in the isolated cortex than in the intact. The distribution of active cells by depth in the neuronally isolated cortex varies from one region to another.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 475–481, September–October, 1970.