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Type 2 diabetes mellitus (T2D), characterised by peripheral insulin resistance, is a risk factor for dementia. In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. In this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain. Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. Integrated Molecular Pathway Level Analysis was performed using the Kyoto Encyclopaedia of Genes and Genomes database on significantly differentially expressed genes, defined as P

The pattern of ocular dominance columns in primary visual cortex of mammals such as cats and macaque monkeys arises during development by the activity-dependent refinement of thalamocortical connections. Manipulating visual experience in kittens by the induction of squint leads to the emergence of ocular dominance columns with a larger size and larger column-to-column spacing than in normally raised animals. The mechanism underlying this phenomenon is presently unknown. Theory suggests that experience cannot influence the spacing of columns if the development proceeds through purely Hebbian mechanisms. Here we study a developmental model in which Hebbian mechanisms are complemented by activity-dependent regulation of the total strength of afferent synapses converging onto a cortical neurone. We show that this model implies an influence of visual experience on the spacing of ocular dominance columns and provides a conceptually simple explanation for the emergence of larger sized columns in squinting animals. Assuming that during development cortical neurones become active in local groups, which we call co-activated cortical domains (CCDs), ocular dominance segregation is controlled by the size of these groups: (1) Size and spacing of ocular dominance columns are proportional to the size s of CCDs. (2) There is a critical size s* of CCDs such that ocular dominance columns form if sBs* but do not form spontaneously if s\s*. This critical size of CCDs is determined by the correlation functions of activity patterns in the two eyes and specifies the influence of experience on ocular dominance segregation. We show that s* is larger with squint than with normal visual experience. Since experimental evidence indicates that the size of CCDs decreases during development, ocular dominance columns are predicted to form earlier and with a larger spacing in squinters compared to normal animals. © 2000 Editions scientifiques et medicales Elsevier SAS

1. Geniculocortical Y-axons (n = 38) in the optic radiations of 4-5-week-old kittens (n = 20) and adult cats (n = 18) were studied both physiologically and morphologically. Axons were recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in visual cortex (particularly well for those innervating area 18). Fourteen axons appeared to be completely filled with HRP (n = 8 in kitten, n = 6 in adult) and served as the basis for the quantitative analysis of the terminal arborizations reported in this study. 2. The distribution and correspondence of the axonal boutons to presynaptic elements in cortical layer 4A was analysed at both the light and electron microscope level using computerized three-dimensional analysis and serial section reconstruction, respectively. Compared to adult axons, the boutons of the kitten axons were smaller (means = 0.75 vs. 1.75 microns length, P less than 0.001) and more densely spaced both along individual axon branches (means = 6.60 vs. 11.20 microns interbouton interval, P less than 0.001) and between neighbouring branches of the same axon (means = 4.7 vs. 6.4 microns nearest-neighbour distance, P less than 0.01). 3. Most kitten boutons made a single Gray's type 1 synapse on a cortical neurone, unlike adult boutons which usually contacted two or more postsynaptic targets. Both kitten and adult axons had dendritic spines as their major target. Occasionally, HRP reaction-product was observed in cortical neurones postsynaptic to the labelled geniculocortical axon, which gave some estimate of the number of synaptic contacts between a single geniculocortical axon and target cell (about five). 4. The kitten Y-axons innervated the visual cortex in a pattern similar to that of the adult, with the richest terminal branching and bouton density in layer 4A with some additional boutons distributed in layers 3, 4B and 6. The extent of the terminal arborizations primarily in layer 4A (as measured in surface views) of kitten Y-axons in area 18 was significantly less than that of adult Y-axons in area 18 (means = 0.9 mm2 vs. means = 1.2 mm2, P = 0.04). 5. We conclude that between 4 and 5 postnatal weeks and 1 year, geniculocortical Y-axons projecting to cortical area 18 undergo four major changes. These include a reduction in synaptic bouton density (both in three-dimensional space and along individual branches), a concomitant moderate expansion in the surface area of cortex innervated, an increase in bouton size and an increase in the number of synaptic contacts made by each bouton. A general proportional growth of the individual axons' terminal arborization together with fusion and/or separation of neighbouring boutons is sufficient to explain this development.

The responses of neurones in the cat's visual cortex are very variable in amplitude. Thus, although the average response amplitude of a single neurone depends closely upon the contrast of a sinusoidal grating, the instantaneous amplitude of the response can convey little information about the grating's contrast. This paper shows that a typical cortical neurone can convey less than one bit of information about contrast in 0.5 s. The amount of information that a neurone can convey is closely correlated with the neurone's responsivity.

p-Tyramine, applied to cortical and caudate neurones with weak iontophoretic currents (0–10 nA), did not usually cause any alteration of base-line firing rate. However, neuronal responses to dopamine (DA) during such weak applications of p-tyramine were greatly enhanced. Cortical neurone responses to noradrenaline (NA) were similarly potentiated, but both cortical and caudate neurone responses to α-aminobutyric acid were unaffected by p-tyramine. In addition, weak background applications of DA which did not affect cell firing rate were also without effect on the neuronal responses to the standard application of DA. The responses of cortical neurones to DA were also potentiated by m-tyramine and β-phenylethylamine applied with weak cationic currents. The results may suggest that trace amines can enhance NA and DA transmission in the central nervous system.

β-Phenylethylamine (PE) potentiates single cortical neurone responses to noradrenaline (NA). The hypothesis that this is due to an action on the noradrenergic presynaptic terminal was tested. Extracellular recordings of the responses of single cortical neurones to iontophoretically applied NA and PE were made in rats with unilateral electrolytic lesions of the locus coeruleus. Ipsilateral lesions blocked responses to PE but did not affect the ability of PE to enhance responses to NA. Contralateral lesions had no effect on either the responses to PE or the enhancement of responses to NA. It is concluded that the PE-induced potentiation of responses to NA is not due to a presynaptic action of PE.

Electrical stimulation of 5-hydroxytryptamine (5-HT) containing cell bodies in the nucleus raphe medianus (NRM) evoked complex responses on most cortical neurones. The predominant response pattern was biphasic, a short latency inhibition being followed by a long latency excitation. Occasional cells showed a third phase, a very long latency weak inhibition. When tryptamine was applied iontophoretically with ejecting currents which did not alter cell firing rate the excitatory effects of NRM stimulation were profoundly reduced. The initial inhibition of cell firing was not altered by tryptamine but some evidence suggested that the long latency inhibition could be potentiated. The results may suggest that tryptamine can modify the neuronal effects of synaptically released 5-hydroxytryptamine.

Responses in the somatosensory cortical area S I to stimulation of facial sinus hairs were recorded in the anaesthetized cat and compared with activity in primary afferent fibres innervating vibrissae follicles. The specific cortical vibrissa area is somatotopically organized; 39% of the cortical units in that area responded to stimulation of only a single sinus hair but in some cases all maxillary vibrissae activated a single cortical neurone. The responses consisted of three major groups; either a phasic discharge in response to the movement part of a stimulus, or an additional tonic discharge related to the steady period of vibrissa deflection, or a tonic discharge. On the basis of a comparison of response and excitability characteristics of primary afferent and cortical neurones it is concluded that all four kinds of peripheral units innervating sinus hair follicles project to the somatosensory cortical area S I. It appears from these findings that some cortical neurones receive a specific input related to a particular component of the complex primary afferent response in fibres innervating sinus hair follicles. The results are discussed with respect to previous reports on the central representation of facial sinus hairs in different species.

The trace amines are a group of endogenous aromatic amines found in low concentrations in the nervous systems of many invertebrate and vertebrate species. They are a diverse group of compounds and it seems likely that they have diverse functions. It has been postulated that trace amines may act as neuromodulators (Boulton, 1976, 1980), false transmitters (Baldessarini, 1974), co-transmitters (Axelrod and Saavedra, 1977), or that they may be neurotransmitters in their own right (Jones, 1982b, Stoof et al. 1976).

Factors regulating somatic growth postnatally have been proposed to affect brain growth and subsequent function when applied prior to birth. This study pertains to the role of growth hormone administered to pregnant rats and the subsequent growth of the progeny. The results showed a significant increase in brain weight and cortical neurone number as determined by the incorporation of labelled thymidine into DNA and subsequent autoradiography. At maturity, learning performance on a series of conditional discrimination tasks was found to be enhanced.

Using electrophysiological techniques the actions of trace amines have been studied at the single cell level in the CNS. The results indicate that many of the neuronal effects of trace amines may be attributable to actions on specific receptors and as such they may possess transmitter function. In addition small amounts of these amines are able to strongly modify neuronal responses to established aminergic and non-aminergic transmitters and may also function as neuromodulators.

A case of encephalopathy, pathologically characterised by loss of cortical neurones, cortical gliosis and cortical and sub-cortical status spongiosus together with proliferation of cortical vessels, is described as an example of Subacute Spongiform Encephalopathy presenting evidence in support of a vascular pathogenesis to this condition.

In the adult brain, cortical neurones that project to other cortical areas have traditionally been classified as either ‘associational’ (having connections within the ipsilateral hemisphere) or ‘callosal’ (projecting to areas in the contralateral hemisphere). Using double-labelling with fluorescent dyes1,2, we have now identified a novel category of mature cortical neurone that has both an ‘associational’ and a ‘callosal’ axon. Such neurones can direct their callosal axons either to a cytoarchitectonic area homotopic to the one in which their cell bodies reside or to an entirely different heterotopic region in the contralateral hemisphere. These cortical neurones with divergent axon collaterals in the adult neocortex differ from recently described neurones that have two axons only transiently during development3–5.