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The emergence and evolution of mammalian neocortex.

Cortical variation in mammals and other terrestrial vertebrates, re-examined by current comparative methodology (out-group analysis), indicates that separate lateral (olfactory), dorsal and medial (hippocampal) pallial or cortical formations arose with the origin of vertebrates. Although the exact origin of mammalian isocortex (so-called neocortex) is still disputed, it appears that the earliest mammals already had a six-layered isocortex with ten to 20 functional subdivisions. Among placental mammals, at least, isocortex has expanded numerous times, producing additional cortical subdivisions. Because these expansions were independent transformations of a simpler cortex, they produced subdivisions that are not homologous.

Animals↗

The organization of neocortex in mammals: are species differences really so different?

By examining a variety of mammals, it is possible to determine common features of cortical organization, and from these infer homologies across species. Such analysis also enables differences in the organization of the neocortex to be identified. Species differ in the amount of cortex that is devoted to a particular sensory system, in the size and configuration of a cortical field, in the number of cortical fields, and in the pattern of connections of homologous fields. It is suggested that the plan of organization that is retained is the result of homologous developmental events, and that modifications to this plan are generated by a limited set of mechanisms. These types of changes to the common network might account for the sensory and behavioural diversity that is observed in extant mammals.

Animals↗

Layer I of primary sensory neocortex: where top-down converges upon bottom-up.

A fundamental paradigm shift is underway in the behavioural neurosciences which promotes renewed discussion of neural correlates of conscious sensation. A growing body of evidence that the primary sensory areas are central to conscious processing is inconsistent with conventional bottom-up models of passive sensory transformation. The new paradigm emphasizes the interaction of top-down corticocortical influences with bottom-up sensory feedback. This review develops the new interactive paradigm with respect to the behaviourally relevant N1 component of the somatosensory evoked response in primary somatosensory neocortex which is only observed during conscious states and predicts touch discrimination behaviour. N1 is generated by layer I excitation apparently in response to backward projections from higher order cortical areas. The backward corticocortical projections mediating top-down influences are anatomically concentrated in layer I where they strongly excite the subpopulation of pyramidal neurons with extensive distal apical dendrites. This subpopulation includes the forward-projecting pyramids subserving corticocortical reentrance as well as the corticobulbar projections mediating cortical control over fine sensory-oriented movements. This interactive paradigm views conscious sensation as an active behaviour with the optimal spatial resolution of primary areas serving as the sensory-motor interface at the major convergence point between reentrant bottom-up and top-down pathways. A device is proposed for the reconstruction of cortical sensory processing based upon the central importance of the primary area as the focus of convergent top-down cortical projections.

Animals↗

Effects of aspiration lesions of hippocampus or overlying neocortex on concurrent and configural object discriminations in rats.

Rats with aspiration lesions of the hippocampus plus overlying neocortex or control lesions of this cortex alone were trained on five-pair concurrent object discriminations in an enclosed Y-maze and subsequently on an open maze. Acquisition of the former task was impaired only in rats with cortical lesions, but on the latter both groups were equally impaired. Recombining positive and negative stimuli into novel pairs did not disrupt performance. Acquisition of single-pair discriminations was normal or slightly impaired in lesion groups. The cortical, but not the hippocampal group, was impaired on the concurrent learning of a positive and a negative pattern configural task. Recombining stimuli did not impair performance of this task either. The study demonstrates that extensive damage to the hippocampal formation need not necessarily impair concurrent learning, and impairments seen in other studies may relate to details of experimental procedure.

Animals↗

The role of brain noradrenaline in cortical activation and behavior: a study of lesions of the locus coeruleus, medial thalamus and hippocampus-neocortex and of muscarinic blockade in the rat.

Local injection of 6-hydroxydopamine in the locus coeruleus resulted in a 90% depletion of noradrenaline (NA) in the cerebral cortex as assessed by high-pressure liquid chromatography. This NA depletion had no effect on scopolamine-resistant hippocampal rhythmical slow activity and only an occasional effect on scopolamine-resistant neocortical low voltage fast activity. However, NE depletion resulted in a slight deficit in a behavioral swim-to-platform test and increased the deficit produced on the test by systemic treatment with scopolamine. Large surgical lesions of the medial thalamus or hippocampal formation plus posterior neocortex greatly increased the behavioral deficit produced by scopolamine. It is concluded that ascending noradrenergic projections play only a modest and possibly indirect role in the control of electrocortical activation and that a number of different brain lesions increase the behavioral impairment produced by central muscarinic blockade.

Animals↗

Non-specific characteristics of intracerebral fiber elongation from the olfactory bulb transplanted into the young adult host neocortex or hippocampal formation, demonstrated immunohistochemically by the mouse Thy-1 allelic system.

The olfactory bulb of an embryo (BALB/c strain mouse) was transplanted into the neocortex or hippocampal formation in a young female adult host (AKR strain mouse) and matured for at least 1 month. Projection fibers from the transplant were demonstrated immunohistochemically using the allelic form of the Thy-1 system between both mice. Fibers from the olfactory bulb transplanted into the frontal cortex showed non-specific elongation in two directions where normally there are no targets of the olfactory bulb fibers: one was toward the cortical surface among radially oriented host fiber systems and another on the corpus callosum running rostrocaudally together with the host's long association bundle. Transplants placed in the hippocampal dentate and hilar regions emit fibers mainly towards the dentate molecular layer and these fibers spread medially and laterally within the molecular layer. The results suggest that projection neurons (mitral and tufted cells) in the transplanted olfactory bulb have the potential ability of non-target-directing axon elongation into the host nerve tissue which usually prevents the penetration of newly growing fibers.

Animals↗

Increased number of somatostatin-immunoreactive neurons in primary cultures of trisomy 16 mouse neocortex.

The gene encoding for pre-prosomatostatin is located on chromosome 16 of the mouse. To determine the effect of an extra copy of this gene on somatostatin expression in neurons, primary disaggregated cultures of neocortex prepared from 15 days gestational Trisomy 16 mice and their littermate euploid controls were subjected to immunocytochemical staining for somatostatin, neuropeptide Y and glutamic acid decarboxylase. The results demonstrate a selective and significant increase in the number of somatostatin-immunoreactive neurons.

Animals↗

Characterization and differential regulation of GABAA and benzodiazepine receptors in rat neocortex.

We have characterized the gamma-aminobutyric acid-A (GABAA) and benzodiazepine (BZ) receptors in in vitro living slices of adult rat neocortex using [3H]SR95531, a GABAA antagonist, and [3H]flunitrazepam (FNZ), a BZ ligand. [3H]SR95531 labelled a single population of GABAA receptors with a Bmax of 1030.7 fmol/mg protein and a Kd of 43.5 nM. [3H]FNZ also labelled a single binding site with a Bmax of 4239 fmol/mg protein and a Kd of 22 nM. The GABAA receptor labelled using [3H]SR95531 could be down-regulated by 2 h preincubations in GABA and the GABAA agonist muscimol (8% and 11%, respectively). Increases in cellular electrical activity induced by a combination of veratridine and glutamate led to an average increase in GABAA receptor number of 58%. The BZ binding site labelled with [3H]FNZ was down-regulated by clonazepam (-55%), increased by GABA (+17%), but not altered by changes in electrical activity. The present results demonstrate the rapid differential regulation of a ligand-gated receptor by agonist stimulation or increases in bioelectric activity. Such regulation may provide clues to the nature of the modifications which occur following changes in cellular activity in the cortex.

Animals↗

Characterization and regulation of a high affinity [3H]CNQX labelled AMPA receptor in rat neocortex.

We have characterized a high affinity site of the alpha-amino-3 hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor in in vitro living slices of adult rat neocortex using [3H]CNQX, and AMPA antagonist. [3H]CNQX labelled multiple binding sites with a Bmax of a high affinity site of approximately 470 fmol/mg protein and an apparent Kd of 11.3 nM. The high affinity site of the AMPA receptor could be down-regulated (36%) by 2 h preincubations in quisqualate, an AMPA agonist. Increases in electrical activity induced by a combination of veratridine and glutamate also led to an average decrease of the high affinity AMPA receptor number of 17%. In addition, preincubations with muscimol, a GABAA agonist, as well as glutamate agonists kainate and N-methyl-D-aspartate (NMDA) led to an average increase in high affinity AMPA receptor number of 17%, 14%, and 37%, respectively. The present results show that a ligand-gated high affinity AMPA receptor can be regulated by agonist stimulation as well as changes in neural activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Age-dependent regulation of GABAA receptors in neocortex.

We have shown previously that GABAA receptors labelled with the antagonist [3H]SR95531 can be regulated in a living cortical slice preparation by agonists or changes in electrical activity. Due to the important role that receptor regulation may play in controlling neural activity, we have now investigated the regulation of GABAA receptors in neocortex at different stages in postnatal life. We found that regulation by agonist stimulation and increases in bioelectric activity is age-dependent in amount and, in the latter case, in direction. Using muscimol as an agonist we observed a GABAA receptor down-regulation of between 60 and 70% at 20-30 days of age; in adults muscimol gave an 11% down-regulation. A combination of veratridine and glutamate gave a peak down-regulation of 39% at 20 days postnatal, but an up-regulation of 58% in adults. These age-dependent effects may signal a role for receptor regulation in cortical neural critical period plasticity.

Aging↗

Expression of the proenkephalin A gene in organotypic cultures of neocortex from newborn rats.

In rats, the proenkephalin A gene is expressed in proliferating cells of the neuroepithelial zone which later give rise to neocortical neurones and glial cells. Therefore, organotypic cultures of neocortex of newborn rats were used in the present study to examine whether neurones as well as glial cells expressed the gene. The slices were prepared at birth and kept in culture for 7-13 days. Proenkephalin mRNA was visualised by in situ hybridisation, while immunocytochemical staining for MAP-2 and GFAP was used to identify neurones and astroglial cells, respectively. In the analysed slices, only neurones contained proenkephalin mRNA. Activation of protein kinase C with tetradecanoylphorbol acetate (1 mumol/l) caused a strong increase in the number of neurones expressing proenkephalin mRNA. Our results indicate that a large number of neurones is able to express the proenkephalin gene under these conditions. However, only a few of them have a basal expression which is strong enough to be detected with in situ hybridisation.

Animals↗

Neurotransmitters in neocortex of aged rhesus monkeys.

The effects of aging on levels of neurotransmitters were determined in two regions of the cerebral cortex in rhesus monkeys (Macaca mulatta). Choline acetyltransferase (ChAT) activity as well as somatostatin, neuropeptide Y, and substance P immunoreactivities were analyzed in the right caudal cingulate gyrus and in the left and right inferior occipital poles in five age groups: 4-6 years; 8-11 years; 20-25 years; 26-29 years; and 31-34 years. Neuroactive amino acids and markers for monoamine transmitters were analyzed only in the youngest (4-6 years) and oldest (31-34 years) animals. Across the five age groups studied. ChAT activity as well as somatostatin and neuropeptide Y immunoreactivities were significantly decreased bilaterally in occipital poles of the 31- to 34-year-old group. There were no significant age-related differences in substance P immunoreactivity. In 4-6-year-old vs. 31-34-year-old monkeys, levels of amino acid neurotransmitters were unchanged. However, there were significant reductions in norepinephrine, serotonin and its metabolites, kynurenine, and 4-hydroxyphenyllactic acid in occipital poles of the 31- to 34-year-old monkeys. No significant neurochemical changes were detected in the cingulate cortex. These findings demonstrate that aged nonhuman primates show reductions in cortical markers for a variety of neurotransmitters, including acetylcholine, somatostatin, neuropeptide Y, norepinephrine, and serotonin but that these changes do not occur uniformly in the neocortex.

Aging↗

Gene expression in Alzheimer neocortex as a function of age and pathologic severity.

Previous studies have shown a marked decline in neuronal and an increase in glial gene expression in Alzheimer's disease (AD) neocortex. Severity of pathologic changes may be greater in presenile AD (PAD) than in senile AD (SAD). We evaluated whether changes in transcript expression were altered as a function of age or pathologic severity. Northern analysis revealed a marked (> 50%) decline in expression of transcripts for the neurofilament light subunit and the major amyloid precursor protein (APP) isoforms in both PAD and SAD. Expression of these neuronal transcripts declined as a function of age in AD and control cases. Expression of the glial fibrillary acidic protein (GFAP) transcript was increased in AD, particularly in the presenile group. AD cases with larger numbers of neurofibrillary tangles had higher levels of GFAP transcript; AD cases with larger numbers of senile plaques had higher levels of APP695 transcript. We conclude that the neuronal mRNA decrements of AD are superimposed on an age-related decline. Age-related shift in expression of certain genes may account for the differences in pathologic severity of PAD and SAD.

Aged↗

Adrenergic and serotonergic receptors in aged monkey neocortex.

Autoradiography was employed to compare the distribution and density of adrenergic (alpha 1, alpha 2, and beta) and serotonergic (5-HT1 and 5-HT2) receptors in the neocortex of young adult (3 to 10 years of age) and aged (> 20 years of age) rhesus monkeys. The age-related changes in the density of adrenergic and serotonergic sites were area and layer specific. A decrease in the density of alpha 1 receptors occurred only in the superficial layers of the somatosensory cortex, whereas the density of alpha 2 receptors declined in layer I of the prefrontal cortex and in most layers of the motor and somatosensory regions. The increase in beta receptors was largely confined to the deep layers of the motor and somatosensory areas. The density of 5-HT1 sites decreased in most layers of the somatosensory cortex, while 5-HT2 receptors declined in the deep layers of the motor cortex and middle strata of the visual cortex. Overall, adrenergic and serotonergic receptors were least affected in the prefrontal cortex and most compromised in the motor and somatosensory cortex of aged primates.

Aging↗

Evidence for the occurrence of early modifications in the 'glia limitans' layer of the neocortex of the reeler mutant mouse.

A comparative EM study of the marginal zone of the neocortex in E15 foetuses of normal and 'reeler' mice was carried out. In the mutant a direct contact between 'proneurons' and the superficial basal lamina bordering the 'glia limitans' layer was observed. Since this phenomenon occurs with a much higher frequency in the mutant than in the normal animal, it is thought to be important in the genesis of the 'reeler' anomaly. In the discussion, different hypotheses concerning the possible nature, mechanism and importance of the interaction described are suggested.

Animals↗

The neocortex of rats behaving in a driven rotating wheel shows a band characterized by preferential uptake of deoxyglucose.

In comparison with control rats placed in a glass chamber, the neocortex of experimental rats performing in a motor-driven activity wheel shows a limited region of high metabolic activity, as revealed by the deoxyglucose radioautographic method. This region consists of a bilateral band located in the somesthetic area SI. An overlap of this labeling with the sensory and/or motor cortical representation of the head, and especially a correlation with head posture and movements, is discussed.

Animals↗

Spontaneous inhibitory postsynaptic potentials in guinea pig neocortex and olfactory cortex neurones.

The membrane potential of olfactory cortex and neocortex neurones in vitro was recorded using conventional microelectrode techniques. During recordings with KCl- or CsCl-filled microelectrodes, spontaneous, subthreshold, transient membrane depolarizations were observed. These were abolished by the GABAA-receptor antagonist, bicuculline methiodide, and were prolonged by the barbiturate pentobarbitone. In most cells they were abolished by tetrodotoxin. It is concluded that these spontaneous depolarizations are inhibitory postsynaptic potentials arising from spontaneous activity in inhibitory interneurones.

Animals↗

Acetylcholinesterase and somatostatin-immunoreactivity coexist in human neocortex.

Immunohistochemistry was combined with enzyme histochemistry to examine the localization of somatostatin (SOM) and acetylcholinesterase (AChE) in the human neocortex. Many of the SOM-immunoreactive cortical neurons were found to display specific AChE activity. Similar coexistence was seen in the rat cortex. In contrast, AChE and SOM appear to be present in distinct cell groups in the human caudate nucleus.

Acetylcholinesterase↗