Jose de Olmos

Mapping of collateral projections with the HRP-method.

Abstract By increasing the sensitivity of a recently developed horseradish peroxidase (HRP) method [2] long axon-collaterals of a retrogradely labeled cell population can be successfully displayed by injecting HRP in one of its terminal fields. The increase in sensitivity has been achieved by introducing certain metal salts into the incubation solution.

“Perestroika” in the basal forebrain: Opening the border between neurology and psychiatry

Publisher Summary This chapter focuses on recent advances in the understanding of basal forebrain organization. Such knowledge forms the necessary conceptual framework for physiologic, behavioral, and clinical studies of forebrain functions relevant to neuropsychiatric disorders. Description of the anatomy of the basal forebrain has touched only peripherally on closely related areas of septal and hypothalamic neuronal systems or the many aspects of diffuse ascending brainstem projections. Nevertheless, considering the strategic position of the three basal forebrain systems discussed in the chapter, and the intimate relation that they have with one another and with other parts of the neuraxis, it is not difficult to envision how disruption of the functional integrity of any one of these systems can easily present itself with a multitude of symptoms that show little regard for traditional boundaries of neurologic and psychiatric disciplines.

Silver Methods for the Impregnation of Degenerating Axoplasm

The reduced silver methods were introduced in the beginning of this century (Ramon y Cajal, 1904; Bielschowsky, 1904), and they were initially appreciated primarily for their remarkable capacity to reveal normal histology and fiber architecture of the brain. Unfortunately, attempts to trace specific fiber systems using these methods were generally unsuccessful, because fiber bundles from a selected neuronal cell group could not be followed with any certainty through the complex meshwork of axons arising from other parts of the nervous system. In the 1930s, neuroanatomists (e.g., Hoff, 1932a,b; Glees and Le Gros Clark, 1941; Glees, 1946) discovered that the capacity of silver stains to identify axons in some stage of Wallerian degeneration* could be utilized to “mark” a system of interest, thus facilitating its recognition as it meandered through the nervous system. Thus, an area of the nervous system could be subjected to an experimental lesion, and, after an appropriate survival interval, the animal could be sacrificed, and its brain processed by a silver method to reveal degenerating axons en route to their destination. Although degenerating axons could usually be distinguished from normal ones in such preparations, evaluating this histological material was tedious, and the results often inaccurate or incomplete. A major breakthrough occurred when Nauta and his colleagues (Nauta, 1950; Nauta and Gygax, 1951, 1954; Nauta and Ryna, 1952) first developed a silver stain that was selective for degenerating neural elements.

Supracapsular bed nucleus of the stria terminalis contains central and medial extended amygdala elements: evidence from anterograde and retrograde tracing experiments in the rat.

Neurons that accompany the stria terminalis as it loops over the internal capsule have been termed collectively the supracapsular bed nucleus of the stria terminalis (BSTS). They form two cell columns, a lateral column and a considerably smaller medial column. The lateral column merges rostrally with the lateral bed nucleus of the stria terminalis and caudally with the central amygdaloid nucleus (central extended amygdala components). The medial column is continuous with the medial bed nucleus of the stria terminalis and the medial amygdaloid nucleus (medial extended amygdala districts). The connections of the BSTS were investigated in the rat by placing injections of Phaseolus vulgaris‐leucoagglutinin (PHA‐L) or retrograde tracers in different parts of the extended amygdala or in structures related to the extended amygdala. BSTS inputs and outputs were identified, respectively, by the presence of varicose fibers and retrogradely labeled neurons within the stria terminalis. The results suggest that the medial‐to‐lateral compartmentalization of BSTS neurons reflects their close alliance with the medial and central divisions of the extended amygdala. The medial BSTS contains primarily elements that correspond to the posterodorsal part of the medial amygdaloid nucleus and the medial column of the posterior division of the medial bed nucleus of the stria terminalis, and the lateral BSTS contains elements that correspond to the medial and lateral parts of the central amygdaloid nucleus and lateral bed nucleus of the stria terminalis. These results add strong support to the concept of the extended amygdala as a ring‐like macrostructure around the internal capsule, and they are of theoretical interest for the understanding of the organization of the basal forebrain. J. Comp. Neurol. 422:533–555, 2000.

Quantitative determination of collateral anterior olfactory nucleus projections using a fluorescent tracer with an algebraic solution to the problem of double retrograde labeling

The bilateral projections of the rat anterior olfactory nucleus (AON) were evaluated using retrograde fluorescent tracers. Competitive effects of these tracers led to severe underestimation of bilaterally projecting neurons, when double-labeled cells were counted. The underestimate was corrected using a numerical approach, which is of general utility for problems in double labeling and requires only a single tracer. With this method we estimated that approximately 63% of AON neurons project bilaterally to the olfactory bulbs, except for the external part which projects exclusively to the contralateral olfactory bulb. No other AON neurons project only to the contralateral bulb.

Transition Areas of the Striatopallidal System with the Extended Amygdala in the Rat and Primate: Observations from Histochemistry and Experiments with Mono- and Transsynaptic Tracer

In several papers we have extensively reviewed the concepts of the ventral striatopallidal system and the extended amygdala (de Olmos et al., 1985; Heimer et al., 1985; Alheid and Heimer, 1988; Alheid et al., 1990; Heimer and Alheid, 1991; Heimer et al., 1991a, 1993), and these topics are only briefly recapitulated here. In some of these (e.g. Alheid and Heimer, 1988; Heimer and Alheid, 1991; Heimer et al., 1993) we have pointed out areas where these two structures are difficult to distinguish; these are the problem areas that we wish to confront in this chapter. In some instances, it is clear that the extended amygdala occupies portions of the forebrain normally considered part of the basal ganglia and more speculatively, we believe that some unusual features in other areas of the basal ganglia might reflect some ectopic elements of the extended amygdala.

Strain and colony differences in the neurotoxic sequelae of MK-801 visualized with the amino-cupric-silver method

The strain and sex of a species under investigation may influence the animals physiological response to a variety of stimuli. Strain and sex differences are important considerations when evaluating animal models. In the rodent MK-801 model of schizophrenia, degenerative changes occur widely in the main olfactory system and in a number of cortical brain regions. In the present report, we compare the effects of MK-801 neurotoxicity in two strains of female rats and also two lines within each strain. The magnitude and regional extent of the neurodegeneration detected with the amino-cupric-silver method varied markedly both between the Sprague-Dawley and Wistar rat strains and also between two lines derived from each strain. For example, terminal degeneration occurred in layer VI of somatosensory cortex and the central extended amygdala in Sprague-Dawley but not Wistar rats. Moreover, MK-801 treatment led to somatodendritic degeneration in the dentate gyrus of the dorsal hippocampus and basolateral amygdala in Wistar rats from Charles River Laboratories but not those from Ferreyra Institute. There are thus both strain and intrastrain differences in the magnitude of the neurodegenerative response to MK-801 treatment. The differing neurotoxicity of MK-801 between rat strains and between lines within a strain may reflect genetic variation and/or differences in hepatic biotransformation and thus the bioavailability of the drug between strains and lines within a strain.