Neocortex Research Articles

Study of the bidirectional transport of choline by blocking choline carriers from outside or inside brain nerve terminals.

Membrane carriers can operate bidirectionally. We studied, in rat neocortex synaptosomes, the choline carrier by comparing the ability of the transport inhibitor hemicholinium-3, present outside or inside the nerve terminals, to prevent uptake and release of [(3)H]choline. Because hemicholinium-3 is membrane-impermeable, it was previously entrapped into synaptosomes during homogenization of brain tissue. External and internalized hemicholinium-3 produced similar maximal inhibition (80-90%) of [(3)H]choline uptake. Also comparable (approximately 30 nM) are the potency of externally applied hemicholinium-3 and the estimated potency of the entrapped inhibitor. Exposure to ouabain elicited release of both [(3)H]acetylcholine and [(3)H]choline from synaptosomes prelabeled with [(3)H]choline. The ouabain (300 microM)-evoked release of [(3)H]choline only was blocked by externally added (IC(50) approximately 10 nM) or internalized (estimated IC(50) approximately 5 nM) hemicholinium-3. Release of previously taken up [(3)H]choline elicited by 100 microM external choline (homoexchange) was prevented by external (IC(50) approximately 30 microM) or entrapped (estimated IC(50) approximately 20 microM) hemicholinium-3. The results suggest that the choline carriers fit into the alternating-access model proposed for classical transmitter transport. Entrapping nonpermeant ligands into synaptosomes could allow investigation of the inward-facing conformation of native transporters and how cytoplasmic ligands affect the bidirectional transport of neurotransmitters.

Dendritic and Synaptic Variety in the Neocortex

(1999). Dendritic and Synaptic Variety in the Neocortex. Developmental Neuropsychology: Vol. 16, No. 3, pp. 311-313.

The Independent Neocortex

The Independent Neocortex

Presence of Sodium Dodecyl Sulfate-Stable Amyloid β-Protein Dimers in the Hippocampus CA1 Not Exhibiting Neurofibrillary Tangle Formation

The amyloid cascade hypothesis of Alzheimer's disease postulates that accumulation of amyloid beta-protein (Abeta) precedes neurofibrillary tangle formation or neuronal loss in the cortex. Although this temporal profile has been proved in the neocortex by silver staining and immunocytochemical methods, CA1 of the hippocampus exhibits a distinct temporal profile during normal aging: the formation of neurofibrillary tangles precedes senile plaque formation. This temporal profile has been further confirmed by two-site enzyme immunoassay (EIA) quantitation of sodium dodecyl sulfate (SDS)-dissociable Abeta42; neurofibrillary tangles are already present despite undetectable levels of SDS-dissociable Abeta42. However, when the same specimens were subjected to Western blotting, many cases with or without neurofibrillary tangles showed some accumulation of SDS-stable Abeta dimers that cannot be detected by EIA. Thus, the temporal profile prerequisite for the hypothesis is still valid in CA1, and this finding also suggests that SDS-stable Abeta dimers have some significant effects on CA1 pyramidal neurons, which are most vulnerable to neurofibrillary tangle formation.

Regulation of cyclic AMP level by progesterone in ovariectomized rat neocortex

Exposure of neocortical slices to progesterone, without prior treatment with estrogen, augmented forskolin-induced cyclic AMP within 15 min. 30 nM progesterone produced approximately 1/2 the maximal effect but as little as 10 nM progesterone produced a detectable increase in cyclic AMP. When forskolin was replaced by dideoxyforskolin, an analog that does not directly stimulate adenylyl cyclase but shares many of its other actions, progesterone did not augment cyclic AMP. Progesterone also failed to affect increased cyclic AMP that followed exposure to norepinephrine or isoproterenol. The effect of progesterone upon cyclic AMP was also evident when tetrodotoxin was added to block voltage-dependent sodium channels, suggesting that intercellular communication that is dependent upon action potentials was not necessary. The effect of progesterone was at least partially blocked by antagonists of GABA A receptor action, suggesting the involvement of GABA A or GABA A-like receptors. The effect of progesterone was also not homogeneous over the neo cortex. While forskolin-stimulated cyclic AMP was augmented by progesterone in the parietal and occipital regions, it was suppressed in the frontal region. These results are envisioned as a progesterone action upon a small and perhaps compartmentalized component of the cellular cyclic AMP system, an effect that is made detectable in our whole-tissue assay by the well known ability of forskolin to potentiate many hormonal effects upon cyclic AMP.

Chronic hypoxia in vivo renders neocortical neurons more vulnerable to subsequent acute hypoxic stress

We studied the neurophysiology of neurons from the central nervous system (CNS) of rats that were exposed to a long-term (3–4 weeks) low oxygen (FiO 2 = 9.5 ± 0.5%) environment ( exposed). Age-matched normoxic animals served as controls (naive). We measured membrane potential ( V m) and input resistance ( R m) at rest and in response to two levels (20% and 0% O 2) of acute in vitro hypoxia using intracellular recordings in the brain slice from two areas of the CNS, layer 23 of the neocortex (NCX) and the hypoglossal nucleus in the brainstem (XII). Resting V m and R m were not different between exposed and naive neurons. However, acute hypoxia elicited dramatic differences between exposed and naive NCX neurons. Exposed NCX depolarized 5 × more (ΔV m = 53.2 ± 7.0mV; n = 13; mean ± S.E.M.) than naive NCX (ΔV m = 10.6 ± 2.0; n = 8) in response to 20% O,. In 0% O 2, naive NCX showed anoxic depolarization (ΔV m > 20mV/min) much sooner (mean latency of 4.8 ± 0.4 min; n = 18) than naive NCX (8.8 ± 1.0 min; n = 19). R m decreased 2–4 times more in exposed NCX compared to naive NCX in response to O 2 deprivation. In addition, while all naive NCX recovered to baseline V m and R m when re-oxygenated, exposed NCX exhibited a much slower recovery compared to naive NCX, and almost 20% of the exposed NCX failed to recover V m and R m following in vitro hypoxia. In contrast to NCX, there was little difference between exposed XII and naive XII. We conclude that chronic hypoxia renders neurons in the neocortex more vulnerable to subsequent acute stress such as O 2 deprivation.

Dynamic shifts in the parameters of the traditional frequency range of the EEG during learning in dogs.

The parameters of the electrical activity of various regions of the neocortex (NC) and the olfactory bulbs (OB) of dogs were studied by means of correlation-spectral analysis during the development of a food-dispenser paw pedal-pressing motor skill; a wide band of frequencies (1-100 Hz), which included both the traditional range (1-20 Hz) as well as high frequencies (HF), were used. Differences were demonstrated in the dynamics of the parameters in the NC and OB. The energy level of the potentials of the NC increased in the HF range (beta 3 and gamma), while in the OB it increased in the HF and alpha range. The coherence-phase characteristics of the NC potentials suggest that more stable (by comparison with resting wakefulness) temporal relationships between the oscillations not only within the limits of HF, but also in the alpha band, are formed in the presence of the developed skill. At the same time, greater phase shifts are characteristic for the interrelationships of the OB potentials and those of the NC, and the increase in coherence relates only to the HF range, whereas the oscillations of the traditional range are characterized by a decrease in coherence. The possible role of the alpha range (along with the HF) in the processing of information which supports appropriate behavior is stressed.

Immunohistochemical evaluation of the cellular localization and ontogeny of 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in the human fetal adrenal gland.

The enzyme, 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase (3 beta-HSD) is an essential element in the biosynthetic pathway for potent adrenal steroid hormones that appear to regulate maturation of many tissues in utero and are critical for homeostasis after birth. The results of prior studies are suggestive that 3 beta-HSD activity in the human fetal adrenal (HFA) is very low and restricted to the outer zone of cortical cells, the neocortex (NC), during mid-gestation. Near the time of birth, however, there must be enhanced expression of this enzyme to allow for adaptation to extrauterine life. In the present study, we sought to characterize, by use of immunohistochemical methods, the cellular localization and developmental changes of 3 beta-HSD in the HFA during the interval of 11-41 wks gestation. Early in gestation, 11-15 wks, we noted considerable 3 beta-HSD in NC and in occasional fetal zone (FZ) cells as well. Thereafter until 24-25 wks, 3 beta-HSD was very low in NC cells and virtually absent from the FZ. Throughout the third trimester, the outer 1/2-2/3 of the NC was increasingly immunostained and clusters of immunoreactive cells also appeared near the central medullary vein of the adrenal. The NC cells and those located in the cortical cuff region that expressed 3 beta-HSD resembled zona glomerulosa cells. Among many other fetal tissues studied, only testicular Leydig cells (18,19 wks) and hilar cells of the ovary (26 wks) were found to contain 3 beta-HSD in quantities sufficient to be detected by immunohistochemistry. These results are suggestive of a heretofore undocumented stimulus to 3 beta-HSD in the HFA in early gestation followed by a suppression of the adrenal concentration of this enzyme during mid-gestation. High levels of 3 beta-HSD in early development may facilitate cortisol production, which is believed to play a role in differentiation of the medullary precursors during this developmental period. The control of adrenal 3 beta-HSD during human fetal development may be more complex than initially envisioned and requires further study.

Relationship between LTD and LTP in neocortex and hippocampus

Relationship between LTD and LTP in neocortex and hippocampus

The evolution of ideas concerning the function of the neocortex.

The evolution of ideas concerning the function of the neocortex.

Appearance of dark neurons following anodal polarization in the rat brain.

An anodal direct current of 3.0 microA or 30.0 microA was unilaterally applied for 30 min or 3 h to the surface of the sensorimotor cortex of rats, and the effects of polarization on the morphology of brain cells were examined by light microscopy. After five repeated anodal polarization trials, dark neurons appeared mainly in the polarized neocortex regardless of the intensity and duration of the polarizing currents. Such dark neurons were scarce in the control animals or the animals receiving only one trial of polarization. The dark neurons were most abundant in the second to fourth layers of the ipsilateral superior-lateral convexity of the frontal cortex, but a few were present in the contralateral cortex. The dark neurons began to appear 24 h after the last polarization; thereafter almost all of these neurons gradually reverted to their normal morphological profiles through a transitory state within 1 month of the last trial of repeated polarization. No morphological changes were apparent in any of the brain structures other than the cerebral cortex. These findings indicate that repeated anodal polarization has reversible morphological effects on the cortical neurons, suggesting that the appearance of dark neurons after anodal polarization is an important index for evaluation of cortical plastic change induced by polarization.

Nucleus cuneiformis lesion increases high-voltage spindle incidence in unrestrained rat neocortex.

The effects of bilateral electrolytical lesions of the mesencephalic nucleus cuneiformis (CU) on both the high-voltage splindle (HVS) activity and the spontaneous behaviour of unrestrained rats have been investigated. In control experiments, EEG spectral power mapping indicated different HVS rhythms in frontal and occipital cortices. The main lesion effect was a strong significant increase of the HVS incidence in the frontal cortex. However, the CU lesion did not affect the incidence of relaxed waking immobility which is specifically related to HVS generation. Furthermore, CU lesion did not alter the power spectra of the frontal cortical EEG during different behavioural states. The results indicate that CU exerts inhibitory influences on the generation of HVSs, which probable correlates with facilitation of the sensory information transfer through the thalamus.

Intact acquisition and long-term retention of mirror-tracing skill in Alzheimer's disease and in global amnesia.

The ability of patients with Alzheimer's disease (AD) or global amnesia (AMN) to acquire skill for tracing a pattern seen in mirror-reversed view and to retain that skill over 24-h intervals was examined. Both patient groups had poor recall and recognition of their mirror-tracing experience, but they acquired and retained mirror-tracing skill as well as normal control subjects. One AMN patient (H.M.) retained the skill over a year-long interval. Furthermore, the patients transferred their skill normally to an alternate pattern. These results indicate that the memory system underlying mirror-tracing skill learning is separable from medial-temporal structures compromised in AMN and AD and from neocortical areas compromised in AD. Brain regions relatively spared in early AD, such as the basal ganglia or cerebellum, may mediate critical aspects of the learning of novel sensorimotor associations that underlie skilled mirror tracing.

Delayed grafting of fetal CNS tissue into chronic compression lesions of the adult cat spinal cord

This review summarizes a series of experiments involving transplants of embryonic feline CNS tissue into chronic compression lesions of the adult cat spinal cord. Fetal spinal cord (FSC), caudal brainstem (BSt), neocortex (NCx) or a combination of either FSC/NCx or FSC/BSt was transplanted as solid pieces or as a suspension of dissociated cells into the developed cystic cavities produced by static-load compression trauma 2-10 weeks prior to grafting. All cats were immunosuppressed with cyclosporin A and their locomotor function was assessed for 6-30 weeks. Following the period of evaluation, all recipients were perfused with fixative and tissue specimens, taken at the transplantation site, were processed for general histological and/or immunocytochemical analysis. Viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. All of the viable intraspinal grafts were extensively vascularized and did not show any signs of imminent or on-going tissue rejection. Fetal cat CNS grafts showed an extended maturational phase in that features of immature neural tissue (e.g. a paucity of myelination) were still seen even 6-9 weeks after transplantation. By 20-30 weeks, FSC and BSt grafts had attained a more advanced stage of maturation. Transplants in these chronic lesions were extensively blended with both the gray and white matter of the host spinal cord and could be visualized by magnetic resonance imaging (MRI). MRI could also detect regions of cavitation at the graft-host interface, as well as within some transplants. While preliminary evidence from behavioral studies suggest that the FSC and BSt grafts may improve or spare locomotor function in some recipients, a more rigorous analysis of post-grafting locomotor function is required to determine conclusively the functionality of these transplants.

Phaclofen: a GABA B blocker reduces long-duration inhibition in the neocortex

Phaclofen: a GABA B blocker reduces long-duration inhibition in the neocortex

Elephants have a large neocortex too

Elephants have a large neocortex too

A classificatory network based on a study of the neocortex

A classificatory network based on a study of the neocortex

The hippocampus and conditioning to contextual cues.

Two experiments are reported in which behavioral control by contextual cues was assessed in groups of rats with dorsal hippocampal (HC), neocortical (NC), or operated control (OC) lesions. Following Odling-Smee's (1975) procedure, a Pavlovian conditioning paradigm was followed in which conditioned stimuli (CSs: tone, light) predicted an unconditioned stimulus (US:footshock) always, never, or half the time. Conditioning trials took place in a small black box. Subsequently, conditioning to background contextual cues was assessed by measuring the amount of time rats spent in the black box in preference to an adjacent white one with neither CS nor US presented. In OC groups and, to a lesser extent, NC groups, conditioning to background cues was inversely related to the probability that CS predicted US. In contrast to graded contextual conditioning in control groups, the HC groups consistently showed abnormally strong conditioning to context that was at or near asymptotic level. The results, which were related to current theories of the relation between contextual stimuli and CSs, suggest that the hippocampus may play an important role in stimulus selection during learning.

Neocortical ultrastructure during rehabilitation after long-term protein-caloric deficiency

Neocortical ultrastructure during rehabilitation after long-term protein-caloric deficiency

Motor Control of the Hand: Hand Function and the Neocortex . A. W. Goodwin and I. Darian-smith, Eds. Springer-Verlag, New York, 1985. x, 314 pp., illus. $34.50. Experimental Brain Research Supplementum 10. From a symposium, Melbourne, Aug. 1983.

Motor Control of the Hand: <i>Hand Function and the Neocortex</i> . A. W. Goodwin and I. Darian-smith, Eds. Springer-Verlag, New York, 1985. x, 314 pp., illus. $34.50. Experimental Brain Research Supplementum 10. From a symposium, Melbourne, Aug. 1983.