Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular basal forebrain in the rat

Abstract

The distribution of presumptive glutamatergic and/or aspartatergic neurons retrogradely labeled following injections of [3H]-D-aspartate into the magnocellular basal forebrain of the rat was compared with the distribution of neurons labeled by comparable injections of the nonspecific retrograde axonal tracer wheat germ agglutinin conjugated to horseradish peroxidase. Cells retrogradely labeled by wheat germ agglutinin-horseradish peroxidase were found in a wide range of limbic and limbic-related structures in the forebrain and brainstem. In the telencephalon, labeled neurons were seen in the orbital, medial prefrontal, and agranular insular cortical areas, the amygdaloid complex, and the hippocampal formation. Labeled cells were also seen in the olfactory cortex, the lateral septum, the ventral striatopallidal region, and the magnocellular basal forebrain itself. In the diencephalon, neurons were labeled in the midline nuclear complex of the thalamus, the lateral habenular nucleus, and the hypothalamus. In the brainstem, labeled cells were found bilaterally in the ventral midbrain, the central gray, the reticular formation, the parabrachial nuclei, the raphe nuclei, the laterodorsal tegmental nucleus, and the locus coeruleus. A significant fraction of the afferents to the magnocellular basal forebrain appear to be glutamatergic and/or aspartatergic. Only a few of the regions labeled with wheat germ agglutinin-horseradish peroxidase were not also labeled with [3H]-D-aspartate in the comparable experiments. Most prominent among the non-glutamatergic/aspartatergic projections were those from fields CA1 and CA3 of the hippocampus, the hilus of the dentate gyrus, the dorsal subiculum, the tuberomammillary nucleus, and the ventral pallidum. In addition, most of the lateral hypothalamic and brainstem projections to the magnocellular basal forebrain were not significantly labeled with [3H]-D-aspartate. In addition to these inputs, a commissural projection from the region of the contralateral nucleus of the horizontal limb of the diagonal band was confirmed with both wheat germ agglutinin-horseradish peroxidase and the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin. This projection did not label with [3H]-D-aspartate or [3H]-GABA, suggesting that it is not glutamatergic/aspartatergic or GABAergic. Furthermore, double labeling experiments with the fluorescent retrograde tracer True Blue and antibodies against choline acetyltransferase indicate that the projection is not cholinergic.

Connections of the nucleus incertus

“…PHA-L injections in the NId labeled a similar but less dense projection to the septal region. A projection from the region of the NI to the medial-diagonal band complex is well established with retrograde tract-tracing methods (Segal and Landis, 1974;Semba et al, 1988;Vertes, 1988;Carnes et al, 1990). Our anterograde tracer analysis has expanded these results by showing that fibers arising from both the NIc and NId are preferentially distributed toward the lateral borders of the medial septal nucleus and tend to avoid its central core.…”

Rhythmical bursts induced by NMDA in guinea‐pig cholinergic nucleus basalis neurones in vitro.

“…In ultrastructural studies of identified cholinergic basal forebrain neurones, it has been found that the synaptic input to these cells is greatest on the dendrites and, in fact, of the highest density upon the distal dendrites (Ingham, Bolam, Wainer & Smith, 1985). Multiple forebrain and brainstem neurones project into the region of the basal forebrain cholinergic neurones and their dendrites (Grove, 1988;Jones & Cuello, 1989) and many of these neurones may release an excitatory amino acid from their terminals (Carnes et al 1990). The basalis neurones appear to receive input, primarily to their dendrites, from the neocortex (Saper, 1984;Lehmann & Saper, 1985), and the cortical projection neurones are known to contain high concentrations of glutamate and glutaminase, a synthetic enzyme for glutamate (Ottersen & Storm-Mathisen, 1984;Kaneko & Mizuno, 1988).…”

“…Such NMDAinduced rhythmic firing has been shown (in vivo or in vitro) for cells located in the spinal cord (Wallen & Grillner, 1987), the nucleus tractus solitarius (Tell & Jean, 1991), the medial vestibular nucleus (Serafin, Khateb, de Waele, Vidal & Miihlethaler, 1992), the abducens nucleus (Durand, 1993), the substantia nigra (Johnson, Seutin & North, 1992;Chergui et al 1993), the caudate nucleus (Herrling, Morris & Salt, 1983), the supraoptic nucleus (Hu & Bourque, 1992), the thalamus (Leresche, Lightowler, Soltesz, JassikGerschenfeld & Crunelli, 1991) and the cerebral cortex (Flatman, Schwindt, Crill & Stafstrom, 1983). Since the basal forebrain is thought to receive an important contingent of glutamatergic fibres from the brainstem reticular formation and from the cerebral cortex (Carnes, Fuller & Price, 1990;Jones, 1994), it would be possible that glutamate, acting on NMDA channels, might also induce rhythmic bursting in nucleus basalis cholinergic neurones. Our results indeed demonstrated that NMDA, and not agonists of the other glutamate receptors, induced the cholinergic neurones. This action depended predominantly on the presence of powerful low-threshold Ca2+ spikes in the cholinergic cells, and differed accordingly in temporal characteristics and ionic mechanisms from that reported for other systems.…”

Neurotensin promotes oscillatory bursting behavior and is internalized in basal forebrain cholinergic neurons

“…If so, an important role of the NT-induced rhythmic bursts may be that of modulating slow forebrain rhythms. The BF projects heavily upon the cortical mantle and receives a direct cortical feedback (Lemann and Saper, 1985;Cames et al, 1990). In addition, both cholinergic and noncholinergic BF neurons project upon the thalamic nucleus reticularis (Steriade et al, 1987), which is a key element in the generation of different forms of oscillatory rhythms in the thalamocortical network (Steriade et al, 1985(Steriade et al, , 1986(Steriade et al, ,1993Steriade and Llinls, 1988;von Krosigk et al, 1993).…”