Hemisphere Neurons Research Articles

Correlated activity of sensorimotor cortex neurons in the left and right hemispheres of the rabbit brain in immobilization catatonia

Spike sequences extracted from multineuron activity from neurons in the sensorimotor cortex, and recorded simultaneously in the left and right hemispheres of the brains of rabbits in the state of immobilization catatonia ("animal hypnosis") and on recovery of animals from this state were analyzed. Cross-correlation analysis of spike flows revealed a temporal relationship between the appearance of neuron spikes in the left and right hemispheres; these were regarded as the mutual influences of these neurons on each other. The intensity of the influences of left hemisphere neurons on cells in the right brain was shown to change significantly in relation to baseline measures at all stages of the experiment and at all of the time points studied. The intensity of the influences of neurons in the right hemisphere on cells in the left hemisphere changed significantly only after animals recovered from the state of immobilization and over much more restricted time periods.

A direct measure of human lateral temporal lobe neurons responsive to face matching

Do the human cerebral hemispheres process faces differently? Clinical lesion observations and primate studies suggest that the right temporal lobe is critical in face processing. Yet, the nature of this relationship remains unclear. Recording from single neurons during a visuospatial (VS)-matching paradigm, we found that 100% of significantly active neurons discriminated matching from perception, bilaterally. Lateralized differences in the nature and timing of responses revealed that the right hemisphere neurons responded earlier, and with uniform frequency reductions. Additional lateralized differences favoring the right hemisphere neurons were found when subjects matched intact faces compared to scrambled faces or complex objects. We conclude that widely distributed neural ensembles are involved in ‘lateralized’ behaviors, but cerebral specialization of face processing is as much a function of the nature and timing of neuronal activity as anatomic location.

Both estrogen receptors and androgen receptors contribute to testosterone-induced changes in the morphology of the medial amygdala and sexual arousal in male rats

In male rats, a steroid-sensitive circuit in the forebrain regulates mating behavior. The masculine phenotype in one component of the circuit, the posterodorsal nucleus of the medial amygdala (MePD), depends on the level of circulating androgens in the adult. To investigate which gonadal steroid receptor(s) mediate sexual arousal and MePD plasticity, adult male rats were castrated and given Silastic capsules containing the nonaromatizable androgen 5α-dihydrotestosterone (DHT), 17β-estradiol (E2), both steroids, or nothing. A fifth group was sham-castrated and treated with blank capsules. DHT treatment was necessary and sufficient to maintain the expression of noncontact penile erections and ultrasonic vocalizations in castrates. E2 had no significant effect on these measures. Both DHT and E2 increased olfactory investigation (“nosepokes”) during the noncontact penile erection test. E2, but not DHT, maintained intromission patterns, while either steroid, alone or in combination, maintained ejaculatory behavior. Regional volume and cell soma size of the MePD both decreased following castration. Additionally, MePD cell size was lateralized, with left hemisphere neurons larger than those on the right, an effect that appeared independent of steroid manipulations. DHT and E2 each maintained neuronal soma size. E2 maintained MePD regional volume more effectively in the left MePD than in the right, which may have been due to a greater sensitivity of the left to both castration and hormone treatment. Thus, both androgen receptors and estrogen receptors appear to participate in sexual behaviors that may be mediated by the MePD in adult rats, and both receptors contribute to the steroid-regulated structural plasticity in this brain region.

Neurons induce GFAP gene promoter of cultured astrocytes from transgenic mice

In order to investigate the influence of neuron-glia interaction on astrocyte differentiation, we used a transgenic mouse bearing part of the gene promoter of the astrocytic maturation marker GFAP linked to the beta-galactosidase (beta-gal) reporter gene. Addition of embryonic cerebral hemisphere (CH) neurons to transgenic CH astrocyte monolayers increased by 50-60% beta-gal positive cell number. Such event was dependent on the brain regional origin of the neurons and was followed by an arrest of astrocytes from the cell cycle and induction of glial differentiation. Time-course assays demonstrated that maximum effect was observed after 24 h of coculture. Addition of conditioned medium (CM) derived from CH neurons also increased beta-gal positive CH astrocytic cell number. However, such CM had no effect on midbrain and cerebellum astroglia. Together, these data suggest that neurons secrete brain region-specific soluble factors which induce GFAP gene promoter, as measured by beta-gal expression, thus suggesting that neuron-glia interaction might induce the astrocytic differentiation program.

Effect of stimulation of the lateral hypothalamus on the correlation of neuron spike activity in the rabbit neocortex.

Cross-correlation and autocorrelation histograms were constructed with the aim of studying correlated spike activity of neurons in the visual and sensorimotor regions of both hemispheres of the rabbit brain before and after stimulation of the right and left lateral hypothalamic regions, which generates food-motivated responses. Stimulation of the left hypothalamus produced larger rearrangements in correlated neuron firing than stimulation of the right hypothalamus. Stimulation of the left hypothalamus, unlike that of the right hypothalamus, was followed by significant increases in the numbers of pairs of left hemisphere neocortical neurons with linked activity, and also induced the sequential firing of neurons in a particular defined order: sensorimotor cortex cells fired first, followed by visual cortex neurons after delays of up to 120 msec. It is concluded that cortical interhemisphere asymmetry in conditions of hunger is associated with nonuniform functioning of the right and left lateral hypothalamic regions.

Magnopyramidal neurons in the anterior motor speech region. Dendritic features and interhemispheric comparisons.

To test the hypothesis that the larger somal size of layer III magnopyramidal neurons in left than in right Brodmann area 45 is associated with greater measures of dendritic arborization in the left hemisphere neurons. A case series involving postmortem human brain specimens was used to compare dendritic parameters of Golgi-impregnated layer III pyramidal neurons in Brodmann area 45 in the left and right hemispheres. A convenience sample consisting of 9 subjects with no known neurologic or psychiatric disorders was obtained at autopsy. Dendritic parameters of the 10 largest Golgi-impregnated layer III pyramidal neurons were measured in each hemisphere of each brain using a eutectic neuron tracing system. The measures examined were somal size, neuron depth, mean segment length, number of branch points, maximal branch order, combined dendritic diameter, total dendritic length, horizontal extent of the dendritic field, and spine density. The Golgi-impregnated slides were also compared with Nissl-stained slides from adjacent blocks to determine the laminar location of the sampled neurons. Although the mean somal size was greater in the left than in the right hemisphere, none of the dendritic parameters examined was larger for the left hemisphere neurons. As expected, total dendritic length was positively correlated to somal size (r = 0.43, P < 001) in the left hemisphere. However, there was no correlation between these parameters in the right hemisphere (r = 0.02, P = .76). The difference between left and right Brodmann area 45 magnopyramidal neurons in the correlation of somal size and dendritic length provides additional evidence of anatomical differences between these 2 populations of neurons. However, the lack of interhemispheric differences in measures of dendritic arborization suggests that additional factors contribute significantly to the marked difference in somal size between the large magnopyramidal neurons in the left and right hemispheres.

Large chondroitin sulfate proteoglycans of developing chick CNS are expressed in cerebral hemisphere neuronal cultures

Chondroitin sulfate proteoglycans (CSPG) of the extracellular matrix may play regulatory roles in central nervous system (CNS) development. We have examined the expression of two large CSPGs of the embryonic chick brain, which can be differentiated using the monoclonal antibodies HNK-1 and S103L, in cultures of embryonic day 6 chick cerebral hemisphere neurons. Western blot analysis following immunoprecipitation and endoglycosidase treatment revealed that these cultures produce S103L- and HNK-1-reactive proteoglycans which are biochemically indistinguishable from the CSPGs (previously) identified in homogenized chick embryo brain extracts. The HNK-1-reactive CSPG accumulated in the medium throughout the course of cultures. In contrast, the S103L-reactive CSPG was found in a neuron-associated form during the period of aggregate establishment in culture, as well as in a soluble form secreted into the medium. Immunocytochemical staining of cultures with the S103L antibody localized reactivity to most neurons during the period of aggregate formation, while neuronal processes and the few flat cells present (presumably neuroblasts and early glia) were negative. Cell selection experiments confirmed that neurofilament-positive cells were the source of the S103L-reactive CSPG. The use of differential fixation techniques suggested that the cell-associated S103L reactivity may be intracellular. Because of this pattern of expression and localization, we propose that the developmentally regulated S103L-reactive CSPG may play a role in neuronal migration arrest and organization of neurons into functional aggregates.

Effects of Carbon Tetrachloride on Perfused Cultures of Hepatic and Neuronal Cells

Cultured hepatocytes and hemisphere neurons from chick embryos and mouse neuroblastoma cells were exposed to carbon tetrachloride (CC14; 0, 1, 2, 3 and 4mM) for 1 hour, using a perfusion system developed for studying the effects of volatile substances. In the perfused cultures, three parameters were compared: lipid peroxidation, membrane integrity and cellular respiration. In addition, cytochrome C oxidase activity was determined after incubation of cell homogenates with CC14. A concentration-dependent increase in lipid peroxidation and membrane permeability was found in the neuroblastoma cells. The hepatocytes responded to a lesser extent with respect to membrane permeability and their lipid peroxidation did not differ from that of controls. The hepatocytes responded with a 35% decrease in respiration when exposed to 3mM CC14, and a 20% decrease in cytochrome C oxidase activity after treatment with 1.5mM CCl4. In the neuronal cells, much smaller decreases in respiration were found and their cytochrome C oxidase activity remained unaffected. These results are very similar to those obtained after incubation in a closed chamber system. However, the perfused cells were found to be less sensitive to CCl4than cells exposed under static conditions.

A muscle-derived substrate-bound factor that promotes neurite outgrowth from neurons of the central and peripheral nervous systems

The development and survival of spinal motor neurons depends upon muscle-derived trophic factors. Some circumstantial evidence suggested to us that the regulatory subunit of cyclic adenosine 3′:5′-monophosphate-dependent protein kinase (cAMP-dPK)-type II might be involved in neuritic outgrowth from spinal neurons. In the present study, we tested a commercial preparation of cAMP-dPK for neurite-promoting activity. Commercial cAMP-dPK-type II from skeletal and cardiac muscles elicited a significant neurite outgrowth from cultured embryonic chicken neurons when the enzyme preparation was bound to polylysine-coated substrata; type I cAMP-dPK from skeletal muscle was ineffective. Neither cAMP-dPK-type I nor -type II had a significant effect on the survival of spinal neurons in culture. Type II cAMP-dPK also stimulated neurite outgrowth from chicken cerebral hemisphere neurons, dorsal root ganglionic neurons, ciliary ganglionic neurons, and rat sympathetic ganglionic neurons in culture. The neurite-promoting activity appears to reside in a contaminant of the preparation since neither the purified regulatory nor catalytic subunits of cAMP-dPK-type II had an effect on neurite outgrowth per se from cultured neurons and since neurite-promoting activity did not correlate with [ 3H]cAMP binding or cAMP-dependent kinase activity. The neurite-promoting protein was then partially purified from commercial cAMP-dPK-type II by gel filtration on Sephadex G-200 followed by ion-exchange chromatography on DE-52 cellulose. Sodium dodecyl sulfate gel electrophoresis of the active protein peak revealed a major protein band (MW 50 kDa) and several minor bands (e.g., MW 200 kDa, 52 kDa, 45 kDa). Also, immunoblot analysis and immunoprecipitation revealed that the partially purified neurite-promoting protein was distinct from laminin, heparan sulfate proteoglycan, nerve growth factor, neural cell adhesion molecule, and fibronectin. Furthermore, the neurite-promoting activity was not diminished by treatment with heparinase nor was it bound to heparin conjugated to Sepharose. Our results demonstrate that a protein unrelated to laminin or its associated macromolecules and which copurifies with the type II cAMP-dPK of striated muscle stimulates neurite outgrowth from neurons of the central and peripheral nervous systems.

Dual actions of phorbol esters to decrease calcium and potassium conductances of mouse neurons

Phorbol esters, which substitute for diacylglycerol to activate protein kinase C, were applied to mouse dorsal root ganglion and cerebral hemisphere neurons in cell culture. The phorbol esters, phorbol 12,13-dibutyrate and 12- O-tetradecanoyl-phorbol-13-acetate, prolonged calcium-dependent action potential duration at resting membrane potential and at more negative membrane potentials but decreased action potential duration following membrane depolarization to less than −45 mV. When calcium and potassium currents were recorded using the single electrode voltage-clamp technique, the phorbol esters were shown to reduce both voltage-dependent calcium and potassium currents. These studies have demonstrated directly that phorbol esters, presumably by activating protein kinase C, can modify more than one membrane conductance in individual neurons.

Phorbol esters: voltage-dependent effects on calcium-dependent action potentials of mouse central and peripheral neurons in cell culture

The beta-phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12,13-dibutyrate (PDBu), which activate protein kinase C, were applied to mouse dorsal root ganglion (DRG) and cerebral hemisphere neurons grown in primary dissociated cell culture. Phorbol esters did not modify the membrane potential or input resistance of either type of neuron. To assess the effects of beta-phorbol esters on voltage-dependent conductances, the effects of PDBu and TPA on action potentials evoked from these neurons were determined. The neurons were bathed in a solution containing 5 mM tetraethylammonium and action potentials that contained sodium and calcium components were evoked. When applied at resting membrane potential and at more negative potentials, PDBu and TPA reversibly increased action potential duration. The alpha-phorbol ester 4-alpha-phorbol, which does not activate protein kinase C, did not modify action potential duration. The effects of the beta-phorbol esters, however, were voltage-dependent. When the neurons were depolarized to membrane potentials less negative than -50 mV, PDBu and TPA reduced action potential duration. The effects of both PDBu (10 nM-1 microM) and TPA (100 pM-100 nM) on action potential duration were dose-dependent. The prolongation of action potentials produced at large negative potentials may be due to a reduction in voltage-and/or calcium-dependent potassium conductance, since the prolongation was associated with a reduction in the potassium-dependent afterhyperpolarization; following membrane depolarization in control solution, action potential duration was increased for several minutes, while the afterhyperpolarization was reduced and, following this prolongation, phorbol esters no longer prolonged the action potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Forskolin and Phorbol Esters Reduce the Same Potassium Conductance of Mouse Neurons in Culture

Second messenger systems may modulate neuronal activity through protein phosphorylation. However, interactions between two major second messenger pathways, the cyclic AMP and phosphatidylinositol systems, are not well understood. The effects of activators of cyclic AMP-dependent protein kinase and protein kinase C on resting membrane properties, action potentials, and currents recorded from mouse dorsal root ganglion neurons and cerebral hemisphere neurons grown in primary dissociated cell culture were investigated. Neither forskolin (FOR) nor phorbol 12,13-dibutyrate (PDBu) altered resting membrane properties but both increased the duration of calcium-dependent action potentials in both central and peripheral neurons. By means of the single-electrode voltage clamp technique, FOR and PDBu were shown to decrease the same voltage-dependent potassium conductance. This suggests that two independent second messenger systems may affect the same potassium conductance.

Rat and mouse identifier sequences are preferentially but not exclusively located in cortical neuronal genes expressed postnatally

A genetic element called the identifier (ID) sequence, highly repeated in the rat genome, has previously been reported to be located in the introns of some genes transcribed in the adult rat brain by RNA polymerase II (Pol II). We show that nuclear RNA isolated from neurons of cerebral hemispheres (cortex) of 14-day old rats is enriched more than 10-fold in ID sequences compared to nuclear RNA from liver, kidney, cerebellum, or cortical glia. The developmental onset of the difference is during the first 2 weeks after birth. Mouse cortical neuronal nuclear RNA is similarly enriched in an element related but not identical to the rat ID element, and the enrichment also has postnatal onset. The enriched appearance of ID sequences in transcripts whose expression is increased postnatally in cortical neurons correlates developmentally and spatially with the transcription of ID elements by RNA polymerase III (Pol III) and with a change in chromatin structure.

Immunocytochemical distribution of transferrin and its receptor in the developing chicken nervous system.

Transferrin is the plasma protein responsible for iron transport in all vertebrates. While transferrin is known to have growth-promoting activity on a variety of cells in culture, the role of transferrin and its membrane receptor in neuronal development is unknown. Using antibodies to transferrin and transferrin receptors, we studied the immunocytochemical localization of transferrin and its receptor in developing chicken neural tissues by the peroxidase-antiperoxidase method. In 5-day-old embryonic brain, germinal cells of the ventricular zone showed a positive reaction for transferrin receptors but were negative for transferrin. By 6-7 days, transferrin-positive cells were seen in the inner layer of the ventricular zone and a few 'patches' of transferrin-positive cells were also seen in the adjacent area. By 10 days, large neurons throughout the brain were strongly positive for transferrin. By 11-16 days, all neurons in the brain showed a strong positive reaction for the protein. Thereafter, the transferrin-positive reaction became gradually weaker in neurons whereas the walls of blood capillaries showed a positive reaction for transferrin. In the adult brain, neurons showed very weak or negative staining. A similar staining pattern for transferrin was observed in the developing spinal cord and dorsal root ganglia (DRG). By 10-12 days, both spinal cord neurons and DRG neurons showed strong reactions for transferrin. Thereafter, the transferrin-positive reaction gradually diminished in older spinal cord neurons and completely disappeared from DRG neurons. Cultured cerebral hemisphere, spinal cord, and DRG neurons showed positive staining reactions for both transferrin and its receptor. Our results suggest that: transferrin is initially taken up by developing neurons from cerebrospinal fluid via receptor-mediated endocytosis; the accumulation of transferrin ultimately reaches a maximum level within immunoreactive neurons and then declines just prior to hatching; in contrast to other CNS neurons, DRG neurons accumulate transferrin only briefly and then become negative for transferrin by immunocytochemistry; and after closure of the blood-brain barrier, transferrin may reach neurons by transport across capillaries into the 'paravascular' spaces. In view of these results, transferrin may play some important but unrecognized role in early neuronal development in vivo as well as in vitro.

Developmental changes in the synthesis of nonhistone nuclear proteins relative to the appearance of a short nucleosomal DNA repeat length in cerebral hemisphere neurons.

Fluctuations in the pattern of synthesis of nonhistone nuclear proteins were noted in cerebral hemisphere neurons during early postnatal development of the rat. Noteworthy changes included the synthesis of an acidic nuclear protein of relative molecular weight 41,000 (41K), two chromatin-associated basic proteins (37K and 38K) and several high molecular weight chromatin acidic proteins. These changes in the synthesis of nonhistone nuclear proteins occur at a developmental stage when a short nucleosomal DNA repeat length has appeared in cerebral hemisphere neurons.