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Results for “neocortex”

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At least 19 recordsLinked to original sources
PubMed1979

Histological and neurochemical effects of fetal treatment with methylazoxymethanol on rat neocortex in adulthood.

Forebrain microencephaly results when developing rats are exposed to methylazoxymethanol acetate (MAM) at 15 days of gestation (DG). This potent alkylating agent is selectively cytotoxic for dividing cells. Since distinct neuronal populations in neocortex vary greatly with respect to timing of mitotic activity during gestation, it was predicted that some groups would be differentially reduced by treatment. Histological examination of neocortex from treated rats grown to adulthood revealed major losses of laminae II--IV with relative preservation of deeper layers. The atrophic adult neocortex was further characterized by assay of several defined pre- and postsynaptic neurochemical markers. Total markers for GABAergic neurons were greatly reduced (glutamate decarboxylase -71%, [3H]GABA synaptosomal uptake -63% and endogenous GABA -59%). Total [3H]GABA binding to cortical membranes was reduced 67%. Total [3H]glutamate synaptosomal uptake and endogenous glutamate were reduced 71% and 65% respectively. In contrast, total presynaptic markers for noradrenergic innervation were minimally altered but concentration of tyrosine hydroxylase, [3H]norepinephrine synaptosomal uptake and endogenous norepinephrine were increased by 275%, 130% and 133%, respectively. Concentration of cholinergic presynaptic markers was also increased (choline acetyltransferase +97%, endogenous acetylcholine +64%) in atrophic cortex, but to a lesser degree than for noradrenergic innervation. Specific binding of muscarinic cholinergic antagonist [3H]quinuclidinyl benzilate and the beta-adrenergic receptor antagonist [3H]dihydroalprenolol was reduced 25% and 29% respectively in treated cortex. Thus, MAM treatment at 15 DG severely reduces intrinsic neuronal populations including GABAergic and glutamatergic neurons, and produces a shrunken cortex relatively hyperinnervated by noradrenergic and cholinergic neurons. MAM-induced microencephaly is a useful model system for producing relatively selective lesions of telencephalic neurons and for study of altered neurochemical relationships following developmentally incurred brain damage.

Acetylcholine↗
PubMed2024

Molecular mechanisms of the specialization of human synapses in the neocortex.

Synapses of the neocortex specialized during human evolution to develop over extended timescales, process vast amounts of information and increase connectivity, which is thought to underlie our advanced social and cognitive abilities. These features reflect species-specific regulations of neuron and synapse cell biology. However, despite growing understanding of the human genome and the brain transcriptome at the single-cell level, linking human-specific genetic changes to the specialization of human synapses has remained experimentally challenging. In this review, we describe recent progress in characterizing divergent morphofunctional and developmental properties of human synapses, and we discuss new insights into the underlying molecular mechanisms. We also highlight intersections between evolutionary innovations and disorder-related dysfunctions at the synapse.

Humans↗
PubMed1975

Chloralose induced alteration of visually evoked response from specific and non-specific regions of cat neocortex.

Visually evoked response (VER) and EEG from the motor cortex (precruciate gyrus) and the visual cortex (marginal gyrus) of cats were recorded from 4 to 7 h after the injection of anesthetic doses of alpha-chloralose. During the recording period the VER from the precruciat gyrus showed a 200-300% increase in amplitude while the VER from the marginal gyrus rarely varied more than 50% in amplitude, and did so independent of the changes in the VER from the precruciate gyrus. The number of large amplitude spikes in the EEG from the precruciate gyrus also increased dramatically during the recording period, but no definite correlation between changes in VER amplitude and in the number of spikes in the EEG could be demonstrated. These observations suggest a functional separation between specific and nonspecific sensory pathways, with the latter showing a considerably greater sensitivity to level of anesthesia.

Animals↗
PubMed1976

Visual evoked potentials during the development of a spiking cobalt focus in rat neocortex.

Averaged visual evoked potentials recorded from three electrode placements in visual cortex in response to single and paired light flashes were acquired from rats with epileptogenic cobalt implants or with stainless-steel control implants. Evoked potentials acquired after computer-detected epileptic spikes were also recorded from rats in the cobalt group. Epileptic spiking began between the 6th and 9th postoperative days and flashes then began to evoke epileptic spikes. Excitability cycles were assessed. On the day showing the maximum rate of spiking, excitability at the site of the cobalt was markedly reduced following flash-triggered or spontaneous epileptic spikes in almost all cases. By contrast, the electrode placement in contralateral homotopic cortex showed nearly normal excitability despite the presence of large amplitude epileptiform spikes and sharp waves projected from the site of the cobalt. The results are discussed with reference to other experimental findings.

Animals↗
PubMed1979

Methylazoxymethanol treatment of fetal rats results in abnormally dense noradrenergic innervation of neocortex.

A single injection of methylazoxymethanol in pregnant rats at 15 days of gestation results in severe cortical atrophy in the offspring. In the adult offspring, the neurochemical markers for the cortical gamma-aminobutyric acid-containing neurons are severely reduced, whereas the noradrenergic markers are minimally altered. Immunohistofluorescence microscopy demonstrates a marked increase in the density of noradrenergic axons which have an abnormal pattern of distribution in the atrophic cortex. The results suggest that the central noradrenergic neurons determine the number of axons to be formed early in brain development, but local factors in the terminal field regulate the ultimate distribution of the noradrenergic axons.

Adrenergic Fibers↗
PubMed1978

Origin of the neocortically monitored theta rhythm in the curarized rat.

An array of epidural electrodes was acutely implanted in locally anesthetized, curarized rats in order to map the surface distribution of rhythmic slow activity (RSA) which appears within the neocortex. Peak amplitudes (of about 122 muV) were centered over the dorsal hippocampus outline. A laminar profile of RSA recorded within the neocortex indicated no shifts in phase relative to a homotopic, epidural electrode. RSA increased slightly in amplitude (mean increase = 53%) at the deepest level or neocortex, but it did not approximate an amplitude peak or null within the neocortex. Multiple-unit activities within the neocortex were not phase-locked to RSA. On the other hand, all of these manifestations of an RSA generator were observed as electrodes passed into the dorsal hippocampus. A unilateral cortical spreading depression (CSD) treatment, which markedly attenuated barbiturate spindles in all subjects (N = 10), usually (N = 7 of 10) had no effect on the neocortically monitored RSA. Dissociations between depressed and non-depressed hemispheres, and between neocortical and hippocampal RSA, were obtained in some subjects during CSD. However, concurrent dissociations were also apparent between recording sites within the hippocampus. It is concluded that the neocortical RSA of rats is passively spread from the underlying hippocampus, and dissociations in neocortical and hippocampal RSA in the rat are secondary to changes in the organization of multiple generators of hippocampal RSA.

Animals↗
PubMed2025

Multiple Psychiatric Traits Enriched for Brain Tissues in the Early Postpartum Period.

BACKGROUND: The perinatal period is a high-risk time for onset of various psychiatric disorders. However, it is unclear how genetic risk factors for these disorders interact with biological changes associated with pregnancy and postpartum. This study evaluates whether psychiatric genome-wide association study (GWAS) results are enriched within various brain regions across the perinatal period. METHODS: Tissue-specific enrichment analyses were conducted to estimate the potential impact of GWAS loci on transcriptional changes in the brain across the perinatal period. GWAS summary statistics were obtained for 26 psychiatric phenotypes. RNA-sequencing data was acquired from four brain regions (hypothalamus, hippocampus, cerebellum, and neocortex) in mice at six timepoints (virgin, 14- and 16-days post-conception, and 1-, 3- and 10-days postpartum). RESULTS: Hippocampus and neocortex in the early postpartum period are significantly enriched (q-value < 0.05) for genetic variants associated with schizophrenia (SCZ), bipolar disorder (BD), depressive symptoms, and major depressive disorder with suicidal features. The most significant enrichment occurred in the neocortex for SCZ and BD, peaking at postpartum day 1 (SCZ p-value = 3.85 &#xd7; 10-8; BD p-value = 6.65 &#xd7; 10-5). In the hippocampus, BD and SCZ were enriched at postpartum day 1 (SCZ p-value = 3.27 &#xd7; 10-3; BD p-value = 4.33 &#xd7; 10-3). No enrichment was observed in cerebellum or hypothalamus for any of the psychiatric traits tested. CONCLUSIONS: The results accord with previous epidemiological studies and provide context in which to interpret GWAS results. Understanding the burden of genetic variants across the perinatal period may help prioritise pathways underlying onset of psychiatric disorders outside of pregnancy and postpartum periods.

Journal Article↗
PubMed1979

Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates.

Endogenous monoamine concentrations and turnover rates vary markedly in different regions of neocortex as well as in various subcortical structures of young adult rhesus monkeys. Monoamine levels and synthesis rates in amygdala, hippocampus, neostriatum, thalamus and brain stem are generally similar to comparable measures previously reported in a variety of species. However, extending and confirming the results of an earlier study, cortical monoamines exhibit topographically specific patterns of distribution. Thus, dopamine concentration is highest in the prefrontal and temporal neocortex; it decreases along the fronto-occipital axis and only trace amounts are detectable in the visual cortex. The distribution of norepinephrine is similar to that of dopamine except that the highest concentrations of norepinephrine are found in somatosensory cortex instead of prefrontal cortex. The pattern of distribution of serotonin is more uniform. However, the distribution of its metabolite, 5-hydroxyindoleacetic acid, is complementary to that of dopamine: the concentration is lowest in prefrontal cortex and highest in posterior regions of the telencephalon. Synthesis of catecholamines as measured by DOPA accumulation in monkeys treated with an aromatic amino acid decarboxylase inhibitor, NSD 1015, generally parallels the distribution of the catecholamines while indoleamine synthesis, as measured by 5-HTP accumulation, is similar to the distribution of 5-hydroxyindoleacetic acid. It may be significant that synthesis rates for the catecholamines are especially high in various areas of association cortex.

Amygdala↗
PubMed1977

Demonstration of bilateral claustro-cortical connections in the cat with the method of retrograde axonal transport of horseradish peroxidase.

The claustrum of the cat was studied to determine the extent of its projection to the cerebral cortex. Neurons in the bilateral dorsal claustrum are labeled by retrograde axonal transport of horseradish peroxidase (HRP) from injection sites of different neocortical areas with preponderance to the ipsilateral side. It is revealed that the dorsal claustrum projects to almost entire regions of the bilateral neocortex and that distribution of labeled neurons in the bilateral claustrum has topographical correspondence, rostro-caudal as well as dorso-ventral, with regard to the sites of injections in the neocortex. No neurons in the ventral claustrum are labeled.

Animals↗
PubMed2008

Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.

Delivery of genes to the brain and spinal cord across the blood-brain barrier (BBB) has not yet been achieved. Here we show that adeno-associated virus (AAV) 9 injected intravenously bypasses the BBB and efficiently targets cells of the central nervous system (CNS). Injection of AAV9-GFP into neonatal mice through the facial vein results in extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. In adult mice, tail vein injection of AAV9-GFP leads to robust transduction of astrocytes throughout the entire CNS, with limited neuronal transduction. This approach may enable the development of gene therapies for a range of neurodegenerative diseases, such as spinal muscular atrophy, through targeting of motor neurons, and amyotrophic lateral sclerosis, through targeting of astrocytes. It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies.

Animals↗
PubMed2025

A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans.

The remarkable ability of a single genome sequence to encode a diverse collection of distinct cell types, including the thousands of cell types found in the mammalian brain, is a key characteristic of multicellular life. While it has been observed that some cell types are far more evolutionarily conserved than others, the factors driving these differences in the evolutionary rate remain unknown. Here, we hypothesized that highly abundant neuronal cell types may be under greater selective constraint than rarer neuronal types, leading to variation in their rates of evolution. To test this, we leveraged recently published cross-species single-nucleus RNA-sequencing datasets from three distinct regions of the mammalian neocortex. We found a strikingly consistent relationship where more abundant neuronal subtypes show greater gene expression conservation between species, which replicated across three independent datasets covering >106 neurons from six species. Based on this principle, we discovered that the most abundant type of neocortical neurons-layer 2/3 intratelencephalic excitatory neurons-has evolved exceptionally quickly in the human lineage compared to other apes. Surprisingly, this accelerated evolution was accompanied by the dramatic down-regulation of autism-associated genes, which was likely driven by polygenic positive selection specific to the human lineage. In summary, we introduce a general principle governing neuronal evolution and suggest that the exceptionally high prevalence of autism in humans may be a direct result of natural selection for lower expression of a suite of genes that conferred a fitness benefit to our ancestors while also rendering an abundant class of neurons more sensitive to perturbation.

Humans↗