Cellular proliferation in the cerebral cortex following neural excitation in rats

Cortical spreading depression (SD) is characterized by propagation of neuronal/glial membrane depolarization throughout the unilateral cerebral cortex and has been linked to several neurological disorders, including migraine aura and epilepsy. SD induction resulted in a dramatic increase in BrdU-incorporated cells in the ipsilateral cortical hemisphere that was dependent on the number of elicited SD. Immunohistochemical studies revealed that 53% of the BrdU-labeled cells in the SD-generated cortex were NG2 immunopositive and 25% were OX-42 immunopositive. The remaining 22% of BrdU-incorporated cells showed no immunoreactivity to GST-rr, GFAP, NeuN, NG2 or OX-42.These data indicate that functional excitation of the cerebral cortex induces proliferative response in cortical cells, which may subsequently differentiate into glial progenitor or microglia within 3 days after stimulation.     

Hypercapnia and acetylcholine release from the cerebral cortex and medulla

1. The cerebral cortex and medulla of fifty-eight anaesthetized dogs released ACh spontaneously through push-pull cannulae after perfusion with the anticholinesterase, sarin. Hypercapnia (12% CO(2)) evoked a significant release of ACh above the basic spontaneous level, from the medullary and cortical areas. Hypercapnia + hypoxia (12% CO(2) + 8% O(2)), in combination, produced an ACh release comparable to hypercapnia; hypoxia (8% O(2)) had no effect in any region.2. Areas in the medullary reticular formation responsive to injections of CO(2)-bicarbonate solutions (;respiratory responsive areas') produced a significant increase of ACh after exposure to hypercapnia or hypercapnia + hypoxia, over that obtained from either the ;non-respiratory responsive areas' of the medulla or the cerebral cortex.3. The evidence supports the concept that ACh may participate as a neurotransmitter within the cerebral cortex and medulla. Also the results would suggest but do not prove, that a cholinergic factor may be a component in respiratory control under certain circumstances, such as exposure to hypercapnia.     

Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins

Cholinergic fibers from the basal forebrain are known to contact cholinoceptive cortical pyramidal neurons. Recent electrophysiological studies have revealed that nicotinic acetylcholine receptors are also present in human cerebrocortical interneurons. A direct visualization of nicotinic receptor subunits in cortical interneurons has, however, not yet been performed. We have applied double-immunofluorescence using antibodies against parvalbumin --a marker for the Chandelier and basket cell subpopulation of interneurons--and to the alpha4 and alpha7 subunit proteins of the nicotinic acetylcholine receptor. The vast majority of the parvalbuminergic interneurons was immunoreactive for the alpha4 and the alpha7 nicotinic acetylcholine receptor. Provided these receptors would be functional--as suggested by recent electrophysiological findings--the connectivity pattern of cholinergic afferents appears much more complex than thought before. Not only direct cholinergic impact on cortical projection neurons but also the indirect modulation of these by cholinergic corticopetal fibers contacting intrinsic cortical cells would be possible.     

Intrinsic excitation in the rat neostriatum mediated by acetylcholine.

Synaptic excitation elicited by local stimulation in neostriatal slices was found to be mediated by acetylcholine (ACh). The synapses generating this excitation belong to intrinsic neurons. Thus, for the first time, direct evidence for the existence of intrinsic excitatory cholinergic neurons in the neostriatum is provided.     

Glycine receptors mediate excitation of subplate neurons in neonatal rat cerebral cortex

The development of the cerebral cortex depends on genetic factors and early electrical activity patterns that form immature neuronal networks. Subplate neurons (SPn) are involved in the construction of thalamocortical innervation, generation of oscillatory network activity, and in the proper formation of the cortical columnar architecture. Because glycine receptors play an important role during early corticogenesis, we analyzed the functional consequences of glycine receptor activation in visually identified SPn in neocortical slices from postnatal day 0 (P0) to P4 rats using whole cell and perforated patch-clamp recordings. In all SPn the glycinergic agonists glycine, beta-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for beta-alanine and taurine. Glycine-induced responses were blocked by the glycinergic antagonist strychnine, but were unaffected by either the GABAergic antagonist gabazine, the N-methyl-d-aspartate-receptor antagonist d-2-amino-5-phosphonopentanoic acid, or picrotoxin and cyanotriphenylborate, antagonists of alpha-homomeric and alpha1-subunit-containing glycine receptors, respectively. Under perforated-patch conditions, glycine induced membrane depolarizations that were sufficient to trigger action potentials (APs) in most cells. Furthermore, glycine and taurine decreased the injection currents as well as the synaptic stimulation strength required to elicit APs, indicating that glycine receptors have a consistent excitatory effect on SPn. Inhibition of taurine transport and application of hypoosmolar solutions induced strychnine-sensitive inward currents, suggesting that taurine can act as a possible endogenous agonist on SPn. In summary, these results demonstrate that SPn express glycine receptors that mediate robust excitatory membrane responses during early postnatal development.     

Formation of complexes of epileptic activity in the cerebral cortex under the influence of a determinant focus induced by acetylcholine

Foci of enhanced excitability, with independent discharge patterns, were created by means of weak solutions of strychnine and penicillin in cats. The creation of a hyperactive focus by means of acetylcholine (ACh) and neostigmine led initially to an increase in the amplitude and frequency of the paroxysmal discharges in the nearest foci of activity, and later in foci remote from the hyperactive focus. Qualitative changes subsequently developed in the pattern of activity of the strychnine and penicillin foci (with the appearance of ACh-activity in them) and a single functional complex of foci with the same discharge pattern as the ACh-focus was formed. The latter thus plays the role of determinant structure. Inhibition of the activity of the determinant focus was followed by disappearance of ACh-activity in the other foci, restoration of original (penicillin or strychnine) activity in them, and destruction of the epileptic complex.Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. Department of Pathological Physiology, N. I. Pirogov Odessa Medical Institute. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 117–121, February, 1979.     

Electrical activity of isolated rabbit cerebral cortex after direct application of acetylcholine

Six weeks after surgical isolation of an extensive region of the rabbit neocortex, chronic experiments were carried out to study the EEG spectrum in baseline conditions and after macroapplication of acetylcholine (ACh) to the isolated cortex. Application of ACh elicited a complex, multiphasic response in the sensorimotor and visual regions of the isolated cortex, which lasted more than 10 min and consisted of an increase in the EEG amplitude with a gradual alteration in rhythmicity: there was an increase in theta activity, and higher-frequency (up to 15 Hz) processes appeared in the EEG trace. In control experiments (rabbits with intact cortex), application of ACh increased the EEG spectral amplitude and peak height. The response of the isolated cortex was interpreted as artificially induced activation, the level of activation determining the EEG spectrum. The differences in the responses of the isolated cortex and intact cortex result from preservation of control of the intact cortex by subcortical structures. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti, Vol. 45, No. 4, pp. 782–790, July–August, 1995.     

Electrophysiological and neuropharmacological analysis of interaction between the systems of excitation and inhibition in the cerebral cortex

GABA- and cholinergic substances selectively affect different phases of the restoration cycle of primary somatosensory response in albino rats. The GABA antagonist bicuculline reduced and the deactivation inhibitor valproic acid enhanced depression of the test response when stimulated at pulse intervals of 60–125 msec. The cholinomimetic arecoline enhanced and the cholinolytic amizylum diminished facilitation of test response at intervals of 150–200 msec. The data suggest a dynamic interaction as well as a competition between GABA- and cholimergic systems in processing the sensory input. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 315–318, September, 1997     

Efflux mechanism of phenylalanine and tryptophan in rat cerebral cortex slices

Phenylalanine and tryptophan effluxes from rat cerebral cortex slices were studied in small oscillating superfusion cups. The slices superfused for 120 min gained sodium and water and lost potassium only slightly more than those only preincubated for 30 min. There was a linear correlation between the rates of spontaneous efflux of [³H]phenylalanine and [³H]tryptophan and the phenylalanine or tryptophan contents in the slices. No signs of saturation of the exit were discernible within the amino acid concentration range of 0.1 to 18 mmol per kg slice wet weight. Extracellular histidine, phenylalanine and tryptophan stimulated the efflux of [³H]phenylalanine and [³H]tryptophan by saturable exchange. Only histidine inhibited the efflux intracellularly, while intracellular phenylalanine and tryptophan seemed to enhance it.The results suggest that the efflux of phenylalanine and tryptophan from brain cells is carrier-mediated in the presence of other extracellular amino acids but that spontaneous efflux into amino acid-free medium may mainly occur via non-mediated physical diffusion.