A Search for Discrete Cholinergic Nuclei in the Human Ventral Forebrain

Abstract: Slices cut from five frozen human brains were dissected into 2-mm cubes and assayed for choline acetyltransferase (ChAT) activity and protein content. A pattern of enrichment of ChAT activity was found ventral to the anterior commissure; this finding is consistent with the location of the enzyme in the cells of the nucleus basalis of Meynert. The region beneath the anterior commissure was the only place a discrete enrichment of activity could be found, and the precise topography of the enrichment was somewhat variable from brain to brain. The results are discussed in the light of recent knowledge concerning the source of the cortical cholinergic innervation.     

Morphology of neurons and axon terminals associated with descending and ascending pathways of the lateral forebrain bundle in Rana esculenta

Summary The cells of origin of afferent and efferent pathways of the lateral forebrain bundle were studied with the aid of the cobalt-filling technique. Ascending afferents originated from the lateral thalamic nucleus, central thalamic nucleus, posterior tuberculum and the cerebellar nucleus. They terminated in the anterior entopeduncular nucleus, amygdala and the striatum. Telencephalic projection neurons, which are related to the lateral forebrain bundle, were located mainly in the ventral striatum and the anterior entopeduncular nucleus, but were not so numerous in the dorsal striatum. Irrespective of their location, most of the neurons projecting axons into the lateral forebrain bundle had piriform or pyramidal perikarya. Long apical dendrites usually arborized in a narrow space, whereas widely arborizing secondary dendrites originated from short dendritic trunks. The other neurons that contributed to the lateral forebrain bundle were fusiform or multipolar cells. Striatal efferents terminated in the pretectal area and in the anterodorsal, anteroventral and posteroventral tegmental nuclei.     

Dihydrotetrabenazine Binding and Monoamine Uptake in Mouse Brain Regions

The objective of the present study was to estimate extracellular pH (pHe) and intracellular pH (pHi) during near-complete forebrain ischemia in the rat, and to evaluate the relative importance of lactic acidosis and rise in tissue Pco2 (Ptco2) in causing pHe and pHi to fall. The animals, which were ventilated, normoxic, normocapnic, and normothermic, were subjected to 15 min of ischemia, either without or with 30-60 min of recirculation. Ptco2 was measured with a tissue electrode, pHe with a double-barrel liquid ion-exchanger microelectrode, changes in extracellular fluid (ECF) volume by impedance measurements, tissue CO2 content by a microdiffusion technique, and labile tissue metabolites by enzymatic fluorometric methods. Ischemia caused Ptco2 to rise to between 95 and 190 mm Hg (mean 149 mm Hg), and pHe to fall by 0.45-1.05 units (mean 0.70 units). During recovery, Ptco2 normalized within 5 min and pHe after 15-30 min. During ischemia, high-energy phosphates were depleted and tissue lactate content increased to 15 mumol X g-1. The total CO2 content (Tco2) was minimally or moderately reduced (normal, 11.9 mumol X g-1; range of ischemic values, 7.9-12.1 mumol X g-1), this range probably reflecting variable amounts of remaining blood flow. Impedance measurements demonstrated that ECF volume during ischemia was reduced to 55% of control, with gradual normalization during the first 15-30 min of recirculation. From values for Ptco2, Tco2, [HCO3-]e, and ECF volume, [HCO3-]i and pHi could be calculated. These values pertain to an idealized homogeneous intracellular compartment, and the methods used cannot detect whether different intracellular compartments diverge in their acid-base responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fate of the anterior neural ridge and the morphogenesis of the xenopus forebrain

The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division. © 1995 John Wiley & Sons, Inc.     

Cholinergic innervation of the retrosplenial cortex via the fornix pathway as determined by high affinity choline uptake,choline acetyltransferase activity,and muscarinic receptor binding in the rat

The cholinergic projections from basal forebrain nuclei to the retrosplenial cortex (RSC) have previously been studied using a variety of histological approaches. Studies using acetylcholinesterase (AChE) histochemistry and choline acetyltransferase (ChAT) immunocytochemistry have demonstrated that this projection travels via the cingulum on route to the RSC. Preliminary studies from our laboratory, however, have shown that the fornix may also be involved in this projection. The present study uses the combination of pathway lesions, and the analysis of cholinergic neurochemical markers in the RSC to determine the role of the fornix in the cholinergic projection to the RSC. High affinity choline uptake (HACU) and ChAT activity were measured in the RSC of control rats, animals with cingulate lesions, and animals with fornix plus cingulate lesions. Fornix plus cingulate lesions resulted in significant deceases in HACU and ChAT activity in comparison to cingulate lesions alone. Muscarinic receptor binding was also evaluated in combination with the various lesions, and a significant increase in retrosplenial receptor binding was noted following fornix lesions. Together, these results support the concept of a fornix-mediated cholinergic pathway to the RSC.     

Effects of Frequency and Pattern of Medial Forebrain Bundle Stimulation on Caudate Dialysate Dopamine and Serotonin

In vivo microdialysis was employed to detect changes in extracellular dopamine and serotonin in the rat caudate in response to electrical stimulation of the medial forebrain bundle. Extracellular dopamine concentrations increased linearly as a function of the frequency (4-33 Hz) of evenly spaced stimuli in both the presence and absence of cocaine added to the dialysate. Because dopamine neurons are known to fire in single-spike and burst patterns, stimulation pulses were also delivered in a bursting pattern. The response of extracellular dopamine was augmented in both the presence and absence of cocaine when the same number of stimuli were delivered in bursts as compared to an evenly spaced pattern. Serotonin, which was only assessed in the presence of cocaine, similarly increased linearly with frequency, but, in contrast to the dopamine response, levels of serotonin were not augmented by stimuli presented in bursts. These results suggest that microdialysis can be used to detect physiological changes in synaptic transmitter concentrations.     

Increased Salsolinol Levels in Rat Striatum and Limbic Forebrain Following Chronic Ethanol Treatment

Abstract: Endogenous levels of salsolinol and its methylated metabolite were measured by combined gas chromatography and mass spectrometry in rats chronically exposed to ethanol for 150 days. The chronic ethanol administration produced a significant increase of salsolinol concentrations in dopamine-rich brain areas, e.g., the striatum and the limbic forebrain. A negative correlation was observed between plasma ethanol concentration and the level of salsolinol in the brain. A possible role for salsolinol in the regulation of ethanol drinking and/or in the development of ethanol dependence is discussed.     

Influence of Catecholamines on Migration and Differentiation of GnRH Neurons in Rats

The GnRH producing neurons are the key link of neuroendocrine regulation of the adult reproductive system. Synthesis and secretion of GnRH are, in turn, under the afferent catecholaminergic control. Taking into account that catecholamines exert morphogenetic effects on target cells during ontogenesis, this study was aimed at investigation of the effects of catecholamines on development of GnRH neurons in rats during ontogenesis. We carried out comparative quantitative and semiquantitative analyses of differentiation and migration of GnRH neurons in fetuses of both sexes under the conditions of normal metabolism of catecholamines (administration of saline) or their pharmacologically induced deficiency (administration of -methyl-para-tyrosine). The inhibition of catecholamine synthesis from day 11 of embryogenesis led to an increasing number of GnRH neurons in rostral regions of the trajectory of their migration over the brain: in the area of olfactory tubercles on day 17 and in the area of olfactory bulb on days 18 and 21. In addition, the optical density of GnRH neurons located in the rostral regions of migration was higher in the fetuses after administration of -methyl-para-tyrosine during embryogenesis, as compared to the control. It has been concluded that catecholamines stimulate the migration of GnRH neurons and affect their differentiation.