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Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine.

Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.

Animals↗

Multiple types of nitrogen monoxide synthase-/NADPH diaphorase-containing neurons in the human cerebral neocortex.

Nitrogen monoxide (NO) synthase (NOS)-containing neurons (NOSN) were identified by means of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry in nine areas of the human cerebral neocortex from patients 9-74 years of age. Labeled neurons were analyzed according to their disposition in the various layers of the cortical gray and immediately subjacent white matter, and classified according to their cytological features. The vast majority of NOSN (about 80%) are situated in the subcortical white matter and not in the cortical gray proper. Nevertheless, these NOSN extend their processes into the cortical gray and thus appear to participate in intracortical circuits, along with the minority of NOSN situated in all cortical layers. Although many NOSN are small aspiny local circuit neurons, as reported previously, additional distinct cytological types of NADPH diaphorase-positive neurons were also identified, including: (a) local circuit neurons in layer I; (b) granule cells in layer II, and (c) non-pyramidal neurons with densely spinous dendrites in the white matter immediately under the cortical gray. Processes fulfilling light microscopic criteria for axons were seen in many of the above cell types originating from proximal dendrites and, less frequently, from a presumed axon hillock. Taken together, these observations indicate that NOSN belong to several distinct morphological and presumably functional classes, some of which have a unique or restricted laminar location, raising the possibility that some of these various classes of neurons may be selectively affected or spared in neurodegenerative disorders.

Adult↗

Behavioral consequences of neonatal injury of the neocortex.

Several strains of autoimmune mice spontaneously develop molecular layer ectopias that are similar in appearance to those seen in humans and are caused by disturbances in neocortical neuronal migration. These mice also exhibit behavioral anomalies, some of which correlate with ectopias, others with the immunological disorder. In this study, we induced neocortical ectopias (via puncture wounds) and microgyria (via freezing lesions) in the neocortex of 1-day-old (newborn) mice without immune disorders in an attempt to further disentangle the effects of autoimmunity and of cortical malformation on behavior. In addition, we wished to compare the behavioral effects of small ectopias to larger microgyric lesions. DBA mice were assigned at birth to receive either a puncture wound or freezing lesion of either the left or right hemisphere. An independent group was subjected to sham surgery. In adulthood, these mice were given a battery of tests designed to measure lateralization and learning capacity. Lesioned mice (irrespective of hemisphere or type of damage) performed poorly when compared to sham-operated animals in discrimination learning, in a spatial Morris Maze Match-to-Sample task, and in a Lashley Type III maze. In shuttlebox avoidance conditioning, where immunological disorder has been shown to compromise behavioral performance in autoimmune mice, there was no difference between lesioned and sham animals. These results (1) support the dissociation between the effects of developmental neocortical anomalies and autoimmune disease on behavior (2) reveal similarities between spontaneous and induced neocortical malformations and (3) fail to support a difference in behavioral effects between ectopias and microgyria.

Animals↗

The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus.

We used in situ hybridization and immunocytochemistry to investigate the presence of GABA in neurons that express the type 3 serotonin receptor (5-HT3R). Quantitative analysis indicated that more than 90% of 5-HT3R expressing cells are GABAergic in the neocortex and hippocampus. The co-existence of 5-HT3R and GABA in cortical and hippocampal neurons indicates that serotonin, via 5-HT3R, can affect GABA release and suggests the participation of 5-HT3R in the inhibitory regulation of forebrain neurons.

Amygdala↗

Cyclic AMP analogues increase excitability and enhance epileptiform activity in rat neocortex in vitro.

Effects of the cyclic AMP agonists 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (CPT-cAMP), dibutyryl cyclic AMP (dbcAMP) and forskolin were studied on extracellular field potentials in rat neocortex slices in vitro. CPT-cAMP and forskolin produced a prolonged enhancement of epileptiform activity resulting from removal of Mg2+ from the bathing medium. DbcAMP had no apparent effect except at high concentrations (1 mM), when it reduced bursting activity. Field potentials observed following electrical stimulation of the corpus callosum in the presence of Mg2+ were enhanced by CPT-cAMP and dbcAMP; however forskolin was without effect. Intracellular recording techniques demonstrated a transient excitatory influence of dbcAMP. The results indicate a role for cyclic AMP in seizure mechanisms.

Animals↗

Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors.

Acamprosate (calciumacetylhomotaurinate) is used therapeutically against relapse in weaned alcoholics. In the present study, the mechanism of action was investigated by making intracellular in vitro and extracellular in vivo recordings from rat neocortical neurons. Acamprosate (0.1-1 mM) added to the perfusion fluid in vitro reduced excitatory and inhibitory postsynaptic potentials and the depolarizing responses evoked by iontophoretic application of the excitatory amino acids, L-glutamate, L-aspartate, L-homocysteate and N-methyl-D-aspartate, but did not alter the responses to gamma-aminobutyric acid. Acamprosate decreased electrical excitability without apparently changing membrane potential, input resistance, afterhyperpolarization, or threshold and amplitude of the action potential. In vivo iontophoretic application of acamprosate reduced the extracellularly recorded unit activity elicited by iontophoretically applied L-glutamate, whereas spontaneous discharges remained unaffected. These data suggest that acamprosate reduces the postsynaptic efficacy of excitatory amino acid neurotransmitters and lowers neuronal excitability in the neocortex of the rat.

Acamprosate↗

Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex.

Postmortem tissue was obtained from six normal and four Down's syndrome brains ranging in age from 12 to 40 weeks postconception. Tissue was processed for electron microscopy using routine osmium and EPTA staining procedures, and to examine synaptic development, photomicrographs were systematically taken throughout the molecular layer of the sensorimotor neocortex. The number of EPTA-stained synapses were consistently greater than the number of osmium-stained synaptic contacts. A progressive increase in synaptic density throughout the range of ages examined was observed for both normal and Down's syndrome tissue. There was also an increase with developmental age in apparent measures of synaptic maturity, e.g., an increased ratio of mature to primitive contacts and asymmetrical to symmetrical contacts. In normal tissue, pre- and postsynaptic membrane lengths were observed to increase with the ages studied, whereas synaptic membrane widths appeared to attain mature values by 29 weeks postconception. Cleft width remained fairly constant to 28 weeks postconception. Although direct statistical comparisons could not be made, in Down's tissue synaptic parameter development was generally less consistent and the parameters appeared to be reduced during the later stages of development studied.

Down Syndrome↗

Influence of anesthesia on spontaneous activity and receptive field size of single units in rat Sm1 neocortex.

Spontaneous and cutaneously driven unit activity was recorded in the hindfoot region of rat Sm1 neocortex under controlled intravenous infusion, at three selected rates, of the steroid anesthetic agent Althesin. Increasing depth of anesthesia decreased average spontaneous firing rates of 67 single units from 2.5 to 11 Hz during light anesthesia to 0 to 2.5 Hz in deep anesthesia. Thresholds to cutaneous stimulation for 58 units were innocuous (from 15 to 190 micron) using a 5-ms ramp displacement of the skin in the center receptive field. Responses from 13 sites on the hindfoot were classified according to response probability for each of the 58 units in reply to stimuli at 1.5 times center receptive field threshold. Small receptive fields were seen only under conditions of deep anesthesia, considerable expansion of both center and excitatory surrounds occurring with lighter anesthesia. Mean values for total receptive field size (center plus surround excitatory receptive field) were 10.8, 7.8, and 3.4 sites, respectively, for light, moderate, and deep anesthesia. The size of the receptive field was also influenced by stimulus repetition rate; moderate increases of this and anesthetic depth could eliminate substantial receptive fields. Surround inhibition of evoked activity was more effective in deeper anesthesia with little effect in light anesthesia. We suggest that receptive field expansion in light anesthesia arises from a relative increase in excitability of afferent pathways and an accompanying increase in the preponderance of surround excitation vis à vis surround inhibition.

Alfaxalone Alfadolone Mixture↗

The fine structure of vascular-astroglial relations in transplanted fetal neocortex.

The vascular development within allografts of rat fetal neocortex was examined ultrastructurally with particular attention to astroglial-endothelial relationships. Grafts placed in the fourth ventricle exhibited a progressive astrogliosis around the host pial or choroidal vessels incorporated within the transplant which was evident by 1 month postoperative. Immunostaining with antisera to laminin showed intense reactivity around such neovessels at the light microscopic level. Transplants located intraparenchymally within the host parietal cortex also developed reactive astroglial "cuffs" around their marginal vessels by 1 week postoperative, although the degree and location of this reaction varied considerably with time. The origin of the reactive astroglia could not be directly determined from this study, but it is possible that they were stimulated by the collagen and fibroblasts present around vascularizing host pial and choroidal vessels in intraventricular grafts and by meningeal elements that entered the wound created for the intraparenchymal grafts. The marked astroglial reactivity within the grafts raises issues concerning their metabolic activity and their intimate relationship with brain endothelium. The close proximity of reactive astroglia to the graft vasculature would not appear to enhance the blood-brain barrier capabilities of transplant neovasculature, especially in intraventricular transplants, as might be suggested by many in vitro studies.

Animals↗

Persistent innervation of the rat neocortex by basal forebrain cholinergic neurons despite the massive reduction of cortical target neurons. II. Neurochemical analysis.

A significant reduction in the activity of cholinergic enzymes in the neocortex is one of the characteristic neurochemical abnormalities in Alzheimer's disease. The withdrawal of cholinergic innervation is thought to be due to atrophy and degeneration of the cholinergic neurons of the basal forebrain, postulated to occur as a consequence of the loss of postsynaptic target neurons and trophic factors synthesized by these target cells. To directly test the dependence of basal forebrain cholinergic innervation on the presence of target neurons, pregnant rats were administered moderate doses of methylazoxymethanol acetate on Gestational Days 14 and 15. This results in a 40-70% reduction of cortical neurons in offspring of treated dams, but has no significant effect on the genesis of basal forebrain cholinergic neurons. In this paper, neurochemical analysis of cholinergic enzymes (ChAT and AchE) in 2-month-old offspring reveals that the basal forebrain innervates the hypocellular cortex in apparently normal fashion, despite the loss of target neurons. The cholinergic innervation of basal forebrain target regions was examined at various times through 20 months of age and was found to retain the initial high levels of enzymatic activity, without any evidence of loss of cholinergic innervation. The preservation of cholinergic innervation over 20 months despite the massive loss of target neurons contradicts the theory of dependence of basal forebrain cholinergic neurons on target-derived trophic support. These results suggest that the degeneration of basal forebrain cholinergic neurons in Alzheimer's disease is due to phenomena more complex than a reduction in the availability of trophic factors.

Acetylcholinesterase↗

Senile changes in the human neocortex and hippocampus compared by the use of the electron and light microscopes.

The severity of certain "senile" changes, namely senile plaques, neurofibrillary tangles and granulovacuolar degeneration in the neocortex and hippocampus, was estimated by light microscopy, in brains obtained at autopsy from 16 cases aged 24 to 93 years. An assessment of certain features of plaques and tangles as well as Hirano-bodies (also associated with senile change) was made by electron microscopy. A statistically significant correlation was found between the electron-microscopic and light-microscopic findings. The findings in an additional 4 cases aged 39 to 65 years in which only the cortex was examined supported the correlation.

Adult↗

Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type.

Ligand binding to alpha 1-, alpha 2- and beta-adrenergic, serotonin, benzodiazepine and GABA receptors was studied in neocortex and hippocampus of controls and patients with senile dementia of the Alzheimer-type. A selective loss of serotonergic binding sites characterised as a loss of both S1 and S2 sites was observed. The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change.

Aged↗

Modulation of mitogen-induced lymphoproliferation by cerebral neocortex.

The influence of the cerebral neocortex on the immunological status was studied in groups of C3H/He mice after lesioning the right or left fronto-parietal cortex. In left lesioned mice, mitogenesis induced either by phytohemagglutinin (PHA) or concanavalin A (Con A) was depressed by about 50% compared to controls. On the contrary, in animals with right lesions, T cell mitogenesis was enhanced by about 140% as compared to controls and by 220-300% as compared to that observed in left lesioned animals. Mitogenesis of B cells induced by lipopolysaccharide was modified by cortical lesions in exactly the same way as that of T cell proliferation although not reaching statistical significance. These results confirm the lateralization in the cortical modulation of the immune system.

Animals↗

Tricyclic antidepressant drug action correlates with its tissue levels in anterior neocortex.

In the behavioral reversal of learned helplessness in the rat by imipramine, a strong correlation is found between "cure" of helplessness and drug level in anterior neocortex, the locus of drug action in this model of depression. This suggests that the delayed onset of therapeutic action of antidepressant drugs is due to the time required to achieve adequate drug levels at the site of their action.

Animals↗

Effects of focal vs generalized kindled convulsions from anterior neocortex or amygdala on CER acquisition in rats.

Kindling of the anterior neocortex (AC) was shown to produce a brief focal motor seizure, characterized by a clonic-tonic-clonic response of the forelimbs with the animal in a prone posture. These same brief seizures, as previously reported, did not produce retrograde amnesia in a CER paradigm. With repeated evocations, over several days, the AC convulsions exhibited a dramatic increase of the second clonic phase (generalized) and came to appear similar to amygdala kindled convulsions. These generalized AC convulsions, like briefly kindled amygdala convulsions, produced good retrograde amnesia for a CER. With extensive amygdala kindling prior to CER training, a severe CER acquisition deficit was observed. These latter as well as other data suggest that protracted amygdala kindling produces a subsequent reduced ability to acquire fear motivated responses.

Amygdala↗

Role of residual anterior neocortex in recovery from neonatal prefrontal lesions in the rat.

Lesions of mediofrontal cortex in adult rats produce behavioral impairments on spatial alternation tasks as well as retrograde degeneration in the mediodorsal thalamic nucleus. The severity of the behavioral deficits and of the thalamic degeneration correlates positively with lesion size. In contrast, similar lesions in neonatal rats (10 days or younger) produce neither spatial alternation deficits nor thalamic degeneration, even after extensive lesions removing all of the mediofrontal cortex. This study examined the possibility that residual anterior cortex remaining intact after early mediofrontal lesions might be involved in the observed anatomical and behavioral sparing. The results show that the sparing of spatial alternation after neonatal frontal cortex lesions does not depend on functional substitution by intact regions of anterior cortex. Neonatal rats receiving extensive lesions including both the medial and orbital frontal cortex or the entire anterior neocortex remained unimpaired on this task. However, these same animals suffered severe retrograde degeneration in the mediodorsal thalamus. Therefore, although some form of neural plasticity cannot be entirely dismissed as the basis for the behavioral results, it seems more likely that behavioral rather than neural plasticity is involved. We suggest that rats deprived of frontal cortex from infancy are able to perform the spatial alternation task in a manner that differs from that used by most intact rats.

Animals↗

Taste discriminations in rats lacking anterior insular gustatory neocortex.

Previous neurobehavioral investigations have demonstrated that the anterior insular gustatory neocortex (AIGN) mediates taste-illness learning. The present experiment evaluated taste discriminations in rats lacking AIGN. Two groups of rats received distinct surgical treatments. One-half of the animals received bilateral electrolytic lesion placements in the AIGN: Remaining animals received anesthesia and scalp incisions only. Following postoperative recovery animals received standard two-bottle preference tests with various concentrations of sucrose to evaluate gustatory reactivity. Animals thereafter received two-bottle discrimination tests with selected sucrose concentrations. At the conclusion of preference tests and discrimination tests with sucrose, preference tests and discrimination tests were conducted with sodium chloride. Following those tests animals received taste aversion conditioning to determine whether or not AIGN lesions impaired taste-illness learning. Results of two-bottle taste tests indicated that AIGN lesions do not obviously alter taste reactivity nor taste discriminations to preferred concentrations of sucrose and NaCl. Anterior insular lesions did, however, impair normal taste aversion learning. These results, in combination with those of previous investigators, provide further evidence that the AIGN preferentially contributes to taste learning functions.

Animals↗

A procedure for culturing rat neocortex explants in a serum-free nutrient medium.

A procedure is described for long-term culturing of rat neocortex explants in a serum-free growth medium. Slices spanning the entire cortical depth from pial to ventricular side are prepared from 6-day-old rat pups. After preincubation in Hanks' balanced salt solution with extra glucose, the explants are placed on polyamide gauze carriers in plastic culture dishes containing serum-free medium. The dishes are continuously rocked during the culture period. After 3 weeks in vitro the explants consist of a three-dimensional network of neural tissue with a mean thickness above the gauze of ca. 100 micron which corresponds with about 8 cell layers. Central necrosis is either fully absent (in one-third of the explants) or restricted to a minimal strip or patch located close to the gauze. From pial to ventricular side, 5 layers can be distinguished which, with respect to cell size and cell density, reflect a histiotypic architecture. The dense neuropil shows abundant axo-dendritic synapses (both on shafts and spines), myelinated fibers, and spontaneous bioelectric activity.

Animals↗