Vasoactive Intestinal Polypeptide (VIP) promotes the hydrolysis of 3H-glycogen newly synthesized from 3H-glucose by mouse cortical slices. This effect occurs rapidly, approximately 50% of the maximal effect being reached within one minute. The maximal effect is achieved after 5 minutes and maintained for at least 25 minutes. Furthermore the glycogenolytic effect of VIP is reversible, and pharmacologically specific. Thus several neuropeptides present in cerebral cortex such as cholecystokinin-8, somatostatin-28, somatostatin-14, met-enkephalin, leu-enkephalin, do not affect 3H-glycogen levels. VIP fragments 6-28, 16-28 and 21-28 are similarly inactive. Furthermore, among the peptides which share structural homologies with VIP, such as glucagon, secretin, PHI-27 and Gastric Inhibitory Peptide, only secretin and PHI-27 promote 3H-glycogen hydrolysis, with EC50 of 500 and 300 nM respectively, compared to an EC50 of 25 nM for VIP. Immunohistochemical observations indicate that each VIP-containing bipolar cell is identified with a unique radical cortical volume, which is generally between 15-60 micrograms in diameter and overlaps with the contiguous domains of neighbouring VIP-containing bipolar cells. Thus this set of biochemical and morphological observations support the notion that VIP neurons have the capacity to regulate the availability of energy substrates in cerebral cortex locally, within circumscribed, contiguous, radial domains.

Animals↗

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Differential vulnerability, connectivity, and cell typology.

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Alzheimer Disease↗

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Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization with amyloid plaques.

In the present study, we examined the relationship between ApoE and amyloid containing profiles within the cerebral cortex of young, middle aged, and aged Rhesus monkeys. Polymerase chain reaction analysis revealed a pattern consistent with the ApoE e4 phenotype in the rhesus monkey similar to that reported in humans. We found numerous ApoE immunoreactive plaques within the temporal neocortex and amygdala, whereas the hippocampus contained only a few such plaques. Although virtually all ApoE-immunoreactive plaques coexpressed beta-amyloid, most plaques were beta A4 positive/ApoE immunonegative within the aged monkey cortex. Moreover, we observed a close correspondence between ApoE and thioflavin-positive (i.e., amyloid) plaques suggesting that ApoE may play a critical role in the conversion of beta A4 to its beta-pleated form. Because ApoE, beta A4 and amyloid are expressed in plaques within the aged Rhesus macaque cortex, this species may provide an in vivo model for investigations aimed at clarifying the interactions between these proteins in normal and pathologic aging.

Aging↗

PubMedDate not supplied

Noradrenergic innervation patterns in three regions of medial cortex: an immunofluorescence characterization.

A homologous antiserum directed against rat dopamine beta-hydroxylase (DBH was used for the immunohistofluorescent visualization of the noradrenergic (NA) innervation of medial cortex in the albino rat. Three cytoarchitectonic divisions of the medial cortex were studied: prelimbic (PL), anterior cingulate (AC), and granular retrosplenial (RSg). Each division of medial cortex possesses a characteristic and distinct pattern and density of NA fibers. The branching patterns and density of the fibers in PL cortex are similar to those of lateral cortex. AC cortex has the lowest density of NA innervation found in the neocortex; there is minimal arborization in layer I, and a very low density of fibers in layers II and III. In contrast RSg is the most densely innervated region, and NA fibers arborize extensively throughout all layers. The dopaminergic (DA) fibers in medial cortex were studied with glyoxylic acid-induced histofluorescence following midbrain lesions of the dorsal noradrenergic bundle (DNB). A laminar complementarity exists in AC cortex such that the DA fibers terminate in layers I-III, while the NA fibers are largely confined to the deep layers. The distinctive patterns of termination of coeruleocortical fibers indicate that in different cortical areas NA axons contact different elements of neuronal circuitry and that there is some degree of specificity in the distribution of NA terminals within the cortex.

Afferent Pathways↗

PubMedDate not supplied

Laminar, tangential and regional organization of the noradrenergic innervation of monkey cortex: dopamine-beta-hydroxylase immunohistochemistry.

An antiserum directed against human dopamine-beta-hydroxylase purified from pheochromocytoma tissue was employed in an immunohistochemical study of the organization of the noradrenergic innervation of monkey neocortex. A detailed description is given of the laminar pattern of noradrenergic innervation in the dorsolateral prefrontal cortex (Brodmann areas 9 and 10) and the primary somatosensory cortex of the postcentral gyrus (Brodmann areas 3,1,2). The noradrenergic innervation of these two regions is similar in the following respects: (1) fibers are present in all six layers, (2) the innervation is dense and terminal-like in layers IV and V, and (3) layer VI is characterized by fibers oriented parallel to the pial surface which follow the contours of the subcortical white matter. However, these regions differ with respect to specific laminar patterns of fiber distribution and orientation and by virtue of the fact that the primary somatosensory cortex has a very dense noradrenergic innervation, while the density of innervation in dorsolateral prefrontal cortex is low relative to the postcentral gyrus and most other neocortical areas. The laminar pattern of noradrenergic innervation in primary visual cortex differs fundamentally from both prefrontal and primary somatosensory cortices. In a separate series of experiments, dorsolateral frontal cortex lesions were used to investigate the intracortical trajectory of noradrenergic fibers. A discrete aspiration lesion confined to the grey matter of the prefrontal cortex led to a substantial loss of noradrenergic fibers in cortical regions caudal to the lesion. The decrease in density of noradrenergic innervation was particularly pronounced in the pre- and postcentral gyri. These results demonstrate that while the noradrenergic innervation of primate cortex exhibits a far greater degree of regional variation than is present in the rat cortex, the tangential intracortical trajectory that is characteristic of the lissencephalic rat brain is also a dominant feature of the noradrenergic innervation of the gyrencephalic primate brain.

Adrenergic Fibers↗

PubMedDate not supplied

Which synapses are affected in aging and what is the nature of their vulnerability? A commentary on "life span and synapses: will there be a primary senile dementia?".

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Adult↗

PubMedDate not supplied

Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys.

The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

Aging↗