Transport of alpha-ketoisocaproate in rat cerebral cortical neurons

Transport of alpha-ketoisocaproic acid (KIC), the product of leucine transamination, was studied in the cerebral cortex cells isolated from the adult rat brain. The process of [(14)C]KIC accumulation was followed in the presence of aminooxyacetate, an inhibitor of transaminases. Accumulation of KIC was not affected by Na(+) replacement, its initial velocity was observed to be higher upon lowering of external pH. Addition of KIC promoted acidification of cytoplasmic pH, monitored with 2'7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. The detected inhibition of KIC accumulation by alpha-cyano-4(OH)cinnamate pointed to an involvement of one of monocarboxylate transporters (MCT), although 4,4'-diisothiocyano-2,2'-stilbenedisulphonate was without effect. Accumulation of KIC was inhibited by lactate; the effect of pyruvate was detected to be much weaker. Other branched-chain alpha-ketoacids (ketoisovalerate, keto-methylvalerate), as well as beta-hydroxybutyrate and valproate decreased the transport of KIC by 30, 60, and 80%, respectively. The observed characteristics of KIC accumulation in the cortical neurons indicate an involvement of one of the MCT transporters. A crucial role of SH group(s) in the process of KIC accumulation, excluding MCT2, indicates the MCT1, although an involvement of another isoform of MCT in the process of KIC transport in neurons from cerebral cortex of adult brain has not been definitely excluded.     

Classification of cortical neurons according to the character of their background impulse activity]

The method of basic components and cluster analysis was used to classify 75 units in the visual cortex of alert rabbits, proceeding from the empiric form of distribution of interspike intervals (DII), the mean frequency of impulsation and the relative number of intervals up to 500 msec. They were classified into nine groups containing from two to twelve units. Besides the cues, used as a basis for classification, the groups of units also differed in the structure of burst activity, the correlation of adjacent intervals and the ratio between the short (up to 20 to 60 msec) and long intervals. The latter served to make suggestions on the genetic affinity of bimodal DII to those with a bend on the waning after the maximum, and on the nature of formation of high frequency bursts and intervals exceeding 20 to 60 msec.     

How the nonlinear voltage dependence of the amplitude of excitatory postsynaptic potentials induced by cerebral cortical neurons affects cortical rhythmic activity

A nonlinear dependence of the amplitude of excitatory postsynaptic potentials on the membrane potentials was derived. The existence of a region of oscillation stability with an increase in the mean value of nonspecific afferent inflow was demonstrated. A high-frequency oscillation component (40–60 Hz) appears with a pronounced increase in the afferent inflow; this can cause instability in oscillations and abnormal brain activity.     

Localization of ATPase in the cerebral cortex and its role in the functional activity of neurons]

By analogy of defensive conditioned reflex formation in rats using a cytochemical method, dependency of localization and concentration of the product of ATP-ase activity on neuronal and synaptic functional activity has been demonstrated. It corresponds to the notion that only a part of the cortical cells are simultaneously at the state of structural-functional activity. The experimental data demonstrate that the CNS excitation in the animals during the process of learning is connected with increasing ATP-ase activity in ultrastructures of the nucleolus, pericaryon and synapses of some neurons participating in the formation of trace processes in the brain.     

Reaction of the cerebral cortical neurons to complete ischemia]

Changes of morphological and neurophysiological characteristics of pyramidal neurons in response to complete ischemia have been studied by means of vital microscopy of cat and rabbit cortex neurons in addition to some other cytological methods. These responses were found to be complex involving phasic changes in the neuron size, membrane potential and redox potential. Neurons of particular types responded to normo- and hypothermic ischemia differently. Pyramidal neurons retained their vital ability for the whole prolonged period of the complete ischemia (up to 40--60 min).     

Effect of morphine on the sensitivity of cerebral cortical neurons to acetylcholine

Sensitivity of sensorimotor cortical neurons to microiontophoretically applied morphine and acetylcholine has been studied in the experiments on unanesthetized rabbits. The predominant reaction to morphine and acetylcholine was decrease and increase in the rate of neuronal impulse activity, respectively. There was no correlation in the responses to morphine and acetylcholine. Atropine failed to influence the morphine effect. When both drugs are simultaneously applied to neurons, morphine decreases both excitatory and inhibitory responses to acetylcholine. This effect of morphine may occur in the case when the drug is applied in doses which do not change spontaneous neuronal activity. On the contrary, excitatory effect of glutamic acid decreased only when morphine was applied in doses causing local anesthetic effect and decreasing background neuronal activity. It is suggested that morphine can exercise a modulating influence on choline receptors of cortical neurons.     

Effect of antibodies to S-100 group proteins on the electrical activity and chemical sensitivity of the cerebral cortical neurons

The influence of antibodies to proteins S-100 group on electrical activity and chemical sensitivity of rabbit cortical neurons has been investigated by means of extracellular recording and microiontophoresis. It has been found that anti-S-100 increase as a rule spontaneous discharge rate of the neurons, decrease, blockade or invert the neuronal responses to acetylcholine, noradrenaline and glutamate action. It is supposed that proteins S-100 group take part in regulation of eleitrogenic and postsynaptic (primarily glutamate- and GABA-ergic) processes of neural and glial cells in the brain.     

Kainic acid increases activity only of some cortical neurons in the rat

The influence of a subconvulsant dose of kainic acid (KA) on the activity of neurons was studied in the sensorimotor cortical area of urethane-anesthetized rats. A total of 41 neurons was recorded, 38 of these in layer V (probably pyramidal cells). The activity of 18 neurons was recorded before as well as more than 30 min after KA administration (6 mg/kg i.p.). Nine out of these 18 neurons increased their firing rate significantly even 20 min after KA injection, whereas the remaining neurons did not change their activity. Altogether, the increase in the firing rate was significant. KA was found to enhance markedly the firing rate of a part of cortical neurons at very early stages of its action.     

Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture

We investigated the effect of human beta-amyloid precursor protein (APP) on rat primary cerebral cortical neurons cultured in a serum-free medium. Two secretory APP species (APP667 and APP592) with and without the protease inhibitor domain were produced by COS-1 cells transfected with APP cDNAs, which encode the N-terminal portions of APP770 and APP695. Both highly purified APP species, when added to the medium, enhanced neuronal survival and neurite extension in a dose-dependent manner with a maximum effect at approximately 100 nM. These results suggest that secreted forms of APP have trophic activity for cerebral cortical neurons.     

Neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter

Axon growth-promoting and -inhibitory molecules are likely to work in concert to promote and guide axons in vivo. In adult mammals, inhibitory molecules associated with myelin in the white matter of the central nervous system (CNS) play an important role in the failure of long-distance axon regeneration. The presence of neurite growth-inhibitory molecules in the adult rat gray matter has not been extensively studied. In this article we describe work on the characterization of neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter using various biochemical and cell culture approaches. We show using a neuronal cell line (NG108–-15 cells) that neurite growth-inhibitory activity is present in membrane preparations of the cortical gray matter. Purified gray matter membranes also induce growth cone collapse of cultured embryonic rat dorsal root ganglion neurons. The inhibitory activity in the membrane preparations is extractable with 3-[(3-cholamidoprophyl)-dimethylammonio]-1-propane-sulfonate, but does not appear to be depleted by various lectins. Western blots and enzyme treatments showed that the inhibitory effect of the gray-matter preparations is not likely to be mediated by myelin-associated inhibitors or chondroitin sulfate proteoglycans. However, tenascin was detected in these samples and may contribute to some of the inhibitory activity. Selective separation of the inhibitory molecules can be achieved by ion-exchange chromatography, which also suggests the presence of multiple inhibitors in cortical gray matter membranes. © 1997 John Wiley & Sons, Inc. J Neurobiol 32 : 671–683, 1997     

Effect of disulfiram on the interconnected activity of cortical neurons in trained cats

The action of disulfiram on interconnected activity of neurones in the visual and motor cortical areas was studied in cats with food-procuring conditioned responses to light. Multiunit activity was recorded from the areas and, by means of amplitude discrimination, separated into impulse flows. Crosscorrelation analysis of the impulse series was used to reveal the character and temporal parameters of interconnected activities of neurones firing in correlation within the limits both of the same cortical area and of the two different ones. A depressing action was shown of the disulfiram on the food-procuring reaction, accompanied by a decrease of the number of pairs of neurones from the visual and motor cortical areas mostly acting in interconnection, interactions with long time delays being mostly affected. The character of action of neighbouring neurones in the visual and motor cortical areas changed in the same direction, expressed in their firing by a "common source" type. The question is discussed of disulfiram influence on interneuronal connections of both types suggesting a decrease of alimentary motivation as well as disturbance of food-procuring conditioned motor coordination.