Stanley Jacobson

Prefrontal granular cortex of the rhesus monkey. II. Interhemispheric cortical afferents.

In 6 adolescent rhesus monkeys, unilateral injections of horseradish peroxidase (HRP) were made into 6 regions on the convexity of the prefrontal granular cortex. The afferents to each zone were considered with respect to whether they were local afferents (from adjacent frontal areas) or distal afferents (from outside frontal lobe). The strongest input onto prefrontal granular cortex comes from the temporal lobe and especially areas in and around the superior temporal gyrus. Area 10 in the frontal pole region receives input primarily from area 22 in the superior temporal gyrus and dorsal portion of the superior temporal sulcus. That portion of area 46 above the principal sulcus receives input primarily from area 22 in the upper bank of the superior temporal sulcus while area 46 below the principal sulcus has input from the insula of the superior temporal sulcus and area 21 in the lower bank of the superior temporal sulcus. The cortex within the concavity of the acurate sulcus differs in that the dorsal half (including areas 46 and 8a) receives input primarily from the dorsal bank and to a lesser degree the insula of the superior temporal sulcus while the ventral portion of this region including areas 45 and 46 receives input primarily from the lower bank of the superior temporal sulcus, inferior temporal gyrus and insula of the superior temporal sulcus. Input was noted from cingulate areas 23 and 24 to all 6 injected regions while retrosplenial cortex was noted to project to all but one of the injected regions, i.e. area 10. In addition, some labeled neurons were seen in area 7 after injections into area 46 and some were also seen in the inferior temporal gyrus and parahippocampal region after injections into the arcuate region. Finally, labeled neurons were noted in area 19 after injections into the ventral portion of the prefrontal granular cortex bounded by the arcuate sulcus. The HRP-positive neurons that comprised the intrahemispheric cortical afferents to prefrontal granular cortex were located primarily in layer iii. They were pyramidal in shape and ranged in size from small to medium. These neurons were found to be distributed in a horizontal band in which the number of labeled neurons waxed and waned, or they were distributed in a patchy or clumped manner. The possibility that both patterns of distribution represent a vertical or columnar organization to these afferent neurons is discussed.

Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress

Stress activates the hypothalamic-pituitary-adrenal axis through release of corticotropin releasing hormone (CRH), leading to production of glucocorticoids that down-regulate immune responses. Acute stress, however, also has proinflammatory effects that seem to be mediated through the activation of mast cells. Stress and mast cells have been implicated in the pathophysiology of various inflammatory conditions, including some in the central nervous system, such as multiple sclerosis in which disruption of the blood-brain barrier (BBB) precedes clinical symptoms. We previously showed that acute restraint stress increases rat BBB permeability to intravenous 99Tc gluceptate and that administration of the “mast cell stabilizer” disodium cromoglycate (cromolyn) inhibits this effect. In this study, we show that the CRH-receptor antagonist Antalarmin blocks stress-induced 99Tc extravasation, whereas site-specific injection of CRH in the paraventricular nucleus (PVN) of the hypothalamus mimics acute stress. This latter effect is blocked by pretreatment of the PVN with cromolyn; moreover, restraint stress cannot disrupt the BBB in the diencephalon and cerebellum of W/Wv mast cell-deficient mice. These results demonstrate that CRH and mast cells are involved in regulating BBB permeability and, possibly, brain inflammatory disorders exacerbated by acute stress.

The tuberoinfundibular system of the rat as demonstrated by immunohistochemical localization of retrogradely transported wheat germ agglutinin (WGA) from the median eminence

The origin of neuronal perikarya which project to the external zone of the median eminence (the tuberoinfundibular neuronal system) was determined in the rat after injection or diffusion of wheat germ agglutinin (WGA) into the median eminence. The retrogradely transported lectin was detected in neurons using an immunohistochemical method based on the peroxidase-antiperoxidase technique. Immunoreactive cell bodies were found both in hypothalamic and extrahypothalamic regions. Within the hypothalamus, the majority of peroxidase-positive cells were present in the dorsomedial and basolateral portions of the arcuate nucleus, regions of the periventricular nucleus, and the preoptic region, particularly at the level of the organum vasculosum of the lamina terminalis (OVLT). Within the extrahypothalamic regions, WGA-positive perikarya were found in the diagonal band of Broca, the region of the medical septum and the brainstem. Only rare cells were labeled in the ventromedial nucleus of the hypothalamus and no cells were labeled in any region of the amygdala. These data demonstrate that neurons with afferent projections to the median eminence are more widely distributed in the rat brain than previously recognized and therefore, that the concept of the tuberoinfundibular neuronal system must be expanded.

Corticothalamic neurons and thalamocortical terminal fields: An investigation in rat using horseradish peroxidase and autoradiography

Subsequent to thalamic injections in rats of horseradish peroxidase (HRP) alone or HRP and [3H]leucine in combination, the cells of origin of the corticothalamic projections and the terminal fields of the thalamocortical projections were identified. HRP-labeled corticothalamic neurons were uniformly found in layers V and VI. They were medium to small in size and always pyramidal in shape with the larger neurons being found in layer V. On the other hand, 3 different patterns for the distribution of thalamocortical terminal fields were observed. The autoradiographic material indicated that in prefrontal cortex the bulk of thalamocortical fibers terminate in layer III while in motor cortex they terminate primarily in layer V. A third pattern was shared by temporal, occipital and parietal cortex where the bulk of thalamocortical fibers terminate preferentially in layer IV. The data derived from the rats which had received thalamic injections of HRP and [3H]leucine in combination indicated that the connections between cortex and thalamus are in general reciprocal. These results are discussed with regard to earlier studies using classical or more recently developed neuroanatomical methods.

The hypothalamic ‘tuberoinfundibular’ system of the rat as demonstrated by horseradish peroxidase (HRP) microiontophoresis

Microiontophoresis of horseradish peroxidase (20%) into the median eminence of the rat has allowed visualization of perikarya and axon projections of the tuberoinfundibular system after retrograde transport. Cells projecting to the median eminence were found in the periventricular regions of the hypothalamus and were particularly pronounced in dorsal portions of the rostral arcuate nucleus, the medial division of the paraventricular nucleus, and within the anterior periventricular nucleus. Labeling of perikarya within the ventromedial nucleus was rarely found. No labeling by HRP was found within cells of the dorsomedial, anterior, suprachiasmatic, preoptic, lateral hypothalamic nuclei or within the septal and amygdaloid nuclei. Axons from identifiably cells were located within the periventricular neuropil and contained within the baso-lateral portions of the hypothalamic-hypophysial tract.

Medial pulvinar afferents to frontal eye fields in rhesus monkey demonstrated by horseradish peroxidase

Abstract Using horseradish peroxidase as a retrograde axoplasmically transported tracer, afferents from medial pulvinar to a region of cortex within the arcuate sulcus roughly coextensive with the frontal eye fields or area 8 could be demonstrated. The relationship between this cortical region and medial pulvinar was found to be topographical. The cells of origin for the afferents to cortex lying between the superior limb of arcuate sulcus and principal sulcus were located in two bands; one ventral and one dorsal in the nucleus. Cells with projections sulcus were found in a band situated midway between the ventral and dorsal limits of medial pulvinar. Most of the labeled cells in medial pulvinar were located in the anterior two-thirds of the nucleus. No afferents from other pulvinar nuclei to this region were noted. A small number of labeled cells in oral pulvinar resulted from injections of the tracer in premotor area. Injections in pre- and postcentral gyri and prefrontal cortex outside of arcuate sulcus did not result in labeled neurons in pulvinar. A discussion of these findings in light of earlier anatomical investigations of cortex within the arcuate sulcus and pulvinar follows a detailed description of the methods used and the results.

Amygdaloid projections to prefrontal granular cortex in rhesus monkey demonstrated with horseradish peroxidase.

The frontal lobe is divided into an agranular motor and premotor region and a more rostral granular prefrontal region 1. The cortical afferent supply to the motor and premotor areas are the primary and secondary somatosensory regions respectively~, a6, while afferents to the granular cortex arise from more widely distributed sites with several afferent systems converging on this region. These systems originate mainly in the association areas of the visual, auditory and somatosensory corticesS,S,14,16. A recent study of the projections of the amygdala v demonstrated efferent connections from this nucleus to the possible homologue of primate prefrontal cortex in the rat and cat 11. In view of this we have studied the connections of the frontal granular cortex in the rhesus monkey using horseradish peroxidase (HRP) in order to determine whether subcortical projections exist from amygdala to this region in monkey. The brains of 8 adolescent rhesus monkeys were used in this study. All animals received unilateral multiple injections of HRP with each single injection consisting of 0.6 #1 of 10~ aqueous solution of the marker. The injections were carried out over 2-5 min to a depth of 2 mm. The animals survived 65-80 h and the perfusion and processing of the brains for H R P was as previously described z°. Every tenth section through the amygdaloid complex was examined bilaterally under both darkand light-field illumination and the location of the labeled neurons was recorded on a sheet of paper with the aid of an X-ray plotter. In order to determine the exact location of the labeled cells in amygdala, the sections were subsequently stained with cresyl violet and each stained section was projected onto the sheet of paper from the x-y recorder so that the boundaries of the individual nuclei could be drawn in and the HRPpositive neurons located with respect to them. The terminology of Lauer 1° and RusseP 9 is used for the subdivisions of amygdala. HRP-positive neurons were seen in all 8 animals in ipsilateral thalamus and in ipsilateral and contraIateral cortex 4, however, in only 4 of the 8 animals were HRPpositive cells seen in the amygdala and they were always observed ipsilateral to the

Immunohistochemical Localization of Retrogradely and Anterogradely Transported Wheat Germ Agglutinin (WGA) within the Central Nervous System of the Rat: Application to Immunostaining of a Second Antigen within the Same Neuron'

Immunohistochemical localization of retrogradely transported wheat germ agglutinin (WGA) is proposed as a sensitive histochemical technique to identify point to point connections within regions of the central nervous system. Injections of WGA into the median eminence of the hypothalamus and the caudate-putamen complex, respectively, were performed to illustrate that this material is rapidly transported over long distances and accumulates within the cytoplasm of neuronal perikarya and their processes. The applicability of this technique to identification of a second antigen within immunoreactive-WGA-labeled neurons is also demonstrated by sequential immunostaining of tyrosine hydroxylase within dopamine-containing cells of the mesencephalon, ipsilateral to an injection in the caudate-putamen complex. This technique is of use in characterizing bioaminergic neurons in the central nervous system and may also be of use in characterizing peptidergic neurons.

Afferent and efferent subcortical projections of behaviorally defined sectors of prefrontal granular cortex.

Although the functional significance of the midprincipalis region is well known, the afferent and efferent connections of this zone, in comparison to the anterior and posterior portions of the cortex lining the principal sulcus, are poorly understood. In 3 animals the retrograde tracer HRP and the anterograde tracers, tritiated proline, lysine and leucine, were injected into the sulcal cortex lining the principal sulcus. The cortex forming the banks of the principal sulcus was divided into anterior, middle and posterior sectors with one animal used for each zone. As expected from previous studies, the heaviest afferents to the cortex forming the principal sulcus were from the parvocellular portions of the medical dorsal nucleus. The medial pulvinar nucleus and the nucleus limitans projected to only the anterior and posterior portions of the cortex lining the principal sulcus. Projections were seen to all 3 sectors from the anterior, midline, intralaminar and lateral thalamic nuclei. Although cells were seen in the hypothalamus following injections in all 3 sectors of the cortex lining the principal sulcus, the heaviest hypothalamic projections were noted after injections into the mid-sector of the cortex. These HRP-positive cells were in the dorsal and lateral hypothalamic area, dorsal medial nucleus and in the lateral mammillary nucleus. These findings link the midprincipalis region with the prefrontolimbic circuit, and suggest that the midprincipalis region, n. medialis dorsalis, the mammillary bodies and perhaps the cingulate gyrus constitute part of an anatomical circuit concerned with memory processes.

Distribution of commissural axon terminals in the rat neocortex

Abstract The corpus callosum of adult albino rats was sectioned and the brain prepared with the Fink-Heimer technique 5 days postoperatively. The laminar distribution of neuron terminations in the cerebral cortex showed three distinct patterns: fronal-parietal-occipital-insular, and a variant in temporal region; cingular; and retrohippocampal. In the first type, the degenerating terminals were more numerous in supragranular than infragranular layer, while in the second type, they were limited to infragranular layers. In the third type, they were confined to supragranular layers. Comparison of the total callosal projection in the rat with that in opossum, racoon, cat, and rhesus monkey shows that the findings in the rat are similar to that in opossum.