Ultrastructure of neurons in the nucleus basalis of Meynert in squirrel monkey

The nucleus basalis of Meynert in the squirrel monkey exhibits numerous labeled neurons following the retrograde transport of horseradish peroxidase from occipital cortical injection sites. The typically large, often clustered, labeled cells are seen most frequently in association with the fibrous bordering structures of the substantia innominata and in the internal and external laminae of the globus pallidus. Ultrastructurally the copious cytoplasm of nucleus basalis neurons abounds with organelles. Large, vacuolated lipofuscin granules proliferate as a function of age and are not evident in younger monkeys. Approximately 4% of the somal surface is occupied by symmetrical synapses with either flat or pleomorphic vesicles. The remainder is covered mostly by neuroglial processes. Somatic spines bearing synapses are occasionally observed. In the neuropil surrounding nucleus basalis somata, the synapses onto dendrites and spines are mostly asymmetrical with large, round vesicles. Labeled nucleus basalis cells in the substantia innominata immediately lateral to the optic tract are larger and rounder than cells in the internal and external pallidal laminae. However, no remarkable ultrastructural differences were observed between nucleus basalis somata in the substantia innominata and external pallidal lamina, or between horseradish peroxidase-labeled and unlabeled large cells.     

Morphological and electrophysiological characteristics of noncholinergic basal forebrain neurons

Cholinergic neurons in the basal forebrain are the focus of considerable interest because they are severely affected in Alzheimer's disease. However, both cholinergic and noncholinergic neurons are intermingled in this region. The goal of the present study was to characterize the morphology and in vivo electrophysiology of noncholinergic basal forebrain neurons. Neurons in the ventral pallidum and substantia innominata were recorded extracellularly, labeled juxtacellularly with biocytin and characterized for the presence of choline acetyltransferase immunoreactivity. Two types of ventral pallidal cells were observed. Type I ventral pallidal neurons had axons that rarely branched near the cell body and tended to have smaller somata and lower spontaneous firing rates than did type II ventral pallidal neurons, which displayed extensive local axonal arborizations. Subtypes of substantia innominata neurons could not be distinguished based on axonal morphology. These noncholineregic neurons exhibited local axon arborizations along a continuum that varied from no local collaterals to quite extensive arbors. Substantia innominata neurons had lower spontaneous firing rates, more variable interspike intervals, and different spontaneous firing patterns than did type II ventral pallidal neurons and could be antidromically activated from cortex or substantia nigra, indicating that they were projection neurons. Ventral pallidal neurons resemble, both morphologically and electrophysiologically, previously described neurons in the globus pallidus, whereas the substantia innominata neurons bore similarities to isodendritic neurons of the reticular formation. These results demonstrate the heterogeneous nature of noncholinergic neurons in the basal forebrain. J. Comp. Neurol. 394:186–204, 1998. © 1998 Wiley-Liss, Inc.     

Collateralization and GAD immunoreactivity of descending pallidal efferents

The first phase of this study involves injecting a different fluorescent retrograde axonal tracer into the subthalamic nucleus, the substantia nigra, and the mesopontine tegmentum. Multiple labeled cells are found within the caudal third of the globus pallidus. The entopeduncular nucleus and adjacent basal forebrain structures such as the substantia innominata, lateral hypothalamus, bed nucleus of the stria terminalis, and central nucleus of the amygdala all exhibit some dye containing cell, although multiple labeled cells are rare. The second phase of this study involves injecting a different fluorescent retrograde tracer into either the substantia nigra, or the mesopontine tegmentum, and subsequent processing of the tissue for glutamic acid decarboxylase (GAD) immunocytochemistry. Many dye and antibody double-labeled cells could be found within the entopeduncular nucleus and the caudal third of the globus pallidus. This is in contrast to the surrounding basal forebrain regions with brainstem efferents which were rarely GAD-positive. This study indicates that the collateral pattern and immunocytochemistry of globus pallidus neurons with descending efferents are distinct from other basal forebrain neurons having similar efferents. These results also extend previous findings and suggest that the neuron of the pallidal complex are heterogeneous with respect to their patterns of projections. In particular, the present findings question previous assumptions concerning the homology of pallidal segments between primate and rodent species.     

Activity of identified cortically projecting and other basal forebrain neurones during large slow waves and cortical activation in anaesthetized rats

To examine the role played by the basal forebrain cholinergic system in cortical activation, neuronal activity was investigated in the globus pallidus and substantia innominata of urethane-anaesthetized rats during large cortical slow waves and spontaneous or elicited low voltage fast activity. An effort was made to identify the neurones by antidromic stimulation from the neocortex (supposedly cholinergic cells) and from the subthalamic nucleus (pallidal cells). Most of the cortically projecting neurones were strongly activated during cortical activation (5-fold increase in firing rate on average), while the discharge rate of pallidal units was increased only slightly (ratio 1.25 on average). In contrast to the cortically projecting cells, some unidentified cells in the substantia innominata fired at a much higher rate during large cortical slow waves as compared to low voltage fast activity. The results are discussed in relation to previous work on the cortically projecting cells and on the mechanisms of cortical activation.     

Organization of the basal forebrain in the cat: localization of -enkephalin, substance P, and choline acetyltransferase immunoreactivity

The present study uses immunocytochemical techniques to determine whether cholinergic basal forebrain neurons in the cat are in a position to receive a homogeneous pattern of inputs, or if specific immunocytochemically defined afferent systems are localized to only selected regions of the basal forebrain. Monoclonal antibodies against choline acetyltransferase (ChAT) were used to identify the location of putative cholinergic neurons which are known to project to the cerebral cortex. In addition, polyclonal antibodies against substance P (SP) or enkephalin (Enk) were used on either adjacent or on the same histological sections reacted for ChAT to identify the neuropeptide plexuses that provide input to the basal forebrain. ChAT-immunoreactive (ChAT-IR) perikarya were located throughout the vertical limb, genu and horizontal limb of the diagonal band of Broca. ChAT-IR neurons also were located within the substantia innominata (SI), within the peripallidal zone around the globus pallidus, and were intercalated within the internal capsule. Enk-IR and SP-IR were used to determine the distribution of putative peptidergic terminals within the basal forebrain. Extensive Enk-IR and SP-IR terminal label was localized within the globus pallidus and the surrounding peripallidal zones, as well as within the SI, whereas the components of the diagonal band of Broca demonstrated negligible Enk-IR and SP-IR label. These data predict that the subdivisions of the cholinergic basal forebrain in the cat do not share a uniform afferent system, and only selective portions of this cholinergic system are in an anatomical position to receive a major direct input from the identified subcortical peptidergic afferents. The segregation of afferents has important consequences in the selective control of cortical function by the cholinergic basalocortical pathway.     

Cholinergic projections from the basal forebrain to the basolateral amygdaloid complex: a combined retrograde fluorescent and immunohistochemical study

We have examined the location of cholinergic and non-cholinergic neurons that project to the rat basolateral amygdaloid nucleus by using choline acetyltransferase (ChAT) immunohistochemistry in combination with retrograde fluorescent tracing on the same tissue section. Since many tracer-and ChAT-positive neurons were identified in basal forebrain areas, including the ventral pallidum, we also stained many of the sections for glutamate decarboxylase, a suitable marker for the delineation of pallidal areas. Cholinergic neurons projecting to the basolateral amygdaloid nucleus were observed in a continuous territory stretching from the dorsal part of ventral pallidum, through sublenticular substantia innominata to ventral parts of globus pallidus and peripallidal areas. Non-cholinergic neurons projecting to the basolateral amygdaloid nucleus were found intermixed within the same structures and constitute approximately 25% of the amygdalopetal projection neurons in these ventral forebrain structures. Since amygdalopetal cholinergic neurons were demonstrated in areas generally recognized as giving rise to cholinergic projections to cerebral cortex, several retrograde double-labeling experiments with two different fluorescent tracers were performed for the purpose of detecting the possible existence of collateral projections. The results obtained showed that the cholinergic basal forebrain neurons in general project to only one forebrain region, and, furthermore, that the cholinergic system consists of partially overlapping subsets of neurons that project to various neocortical and allocortical areas and to the amygdaloid body.     

Direct catecholaminergic-cholinergic interactions in the basal forebrain. II. Substantia nigra-ventral tegmental area projections to cholinergic neurons

Previous observations indicate that the basal forebrain receives dopaminergic input from the ventral midbrain. The present study aimed at determining the topographic organization of these projections in the rat, and whether this input directly terminates on cholinergic neurons. Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into discrete parts of the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNC) labeled axons and terminals in distinct parts of the basal forebrain, including medial and lateral septum, diagonal band nuclei, ventral pallidum, globus pallidus, substantia innominata, globus pallidus, and internal capsule, where PHA-L-labeled terminals abutted cholinergic (choline acetyltransferase=ChAT-containing) profiles. Three—dimensional (3-D) computerized reconstruction of immunostained sections clearly revealed distinct, albeit overlapping, subpopulations of ChAT-immunoreactive neurons apposed by PHA-L-labeled input from medial VTA (mainly in vertical and horizontal diagonal band nuclei), lateral VTA and medial SNC (ventral pallidum and anterior half of substantia innominata), and lateral SNC (caudal half of the substantia innominata and globus pallidus). At the ultrastructural level, about 40% of the selected PHA-L-labeled presynaptic terminals in the ventral pallidum and substantia innominata were found to establish synaptic specializations with ChAT-containing profiles, most of which on the cell body and proximal dendritic shafts. Convergent synaptic input of unlabeled terminals that formed asymmetric synapses with the ChAT-immunoreactive profiles were often found in close proximity to the PHA-L-labeled terminals. These observations show that the cholinergic neurons in the basal forebrain are targets of presumably dopaminergic SNC/VTA neurons, and suggest a direct modulatory role of dopamine in acetylcholine release in the cerebral cortical mantle. © 1996 Wiley-Liss, Inc.     

Topographic analysis of the innervation of the rat neocortex and hippocampus by the basal forebrain cholinergic system

The basal forebrain-cortex connections of the rat were topographically mapped by retrograde tracer methods; and their contribution to the cholinergic innervation of the cortex was assessed by excitotoxin lesions placed in the rostral and caudal aspects of the complex. Discrete injections of tracer into frontal cortex labeled the prominent multipolar acetylcholinesterase (AchE)-positive cells of the ventromedial globus pallidus. Injections of tracer into the parietal cortex labelled cells in the ventral globus pallidus, the underlying substantia innominata, and the lateral hypothalamus. Separate injections of Fast Blue and Nuclear Yellow in the frontal and in the parietal cortex resulted in double-labeled cells in the ventral globus pallidus, which indicates that at least some of these cells may possess collateralizing axons. The cingulate cortex is innervated predominantly by neurons in the nucleus of the horizontal limb of the diagonal band. The occipital cortex was also shown to receive a projection primarily from the nucleus of the horizontal limb of the diagonal band. The hippocampal formation is innervated primarily by cells located in the vertical limb of the diagonal band and in the medial septum. Consistent with the results of the retrograde tracing studies, excitotoxin lesions affecting the diagonal band and medial septum decreased choline acetyltransferase (CAT) activity up to 40% on the occipital cortex and by 64% in the hippocampus, but did not affect CAT activity in the rostral neocortex. In contrast, ibotenate lesions of the caudal ventral globus pallidus and substantia innominata caused decreases in CAT activity in the frontal cortex of up to 65% without affecting enzyme activity in the hippocampal formation. The results of the present study provide details on the topographic organization of the cortical projections originating in the basal forebrain complex and indicate that these neurons are the predominant source of cortical cholinergic innervation.     

Direct catecholaminergic-cholinergic interactions in the basal forebrain. III. Adrenergic innervation of choline acetyltransferase-containing neurons in the rat

The central adrenergic neurons have been suggested to play a role in the regulation of arousal and in the neuronal control of the cardiovascular system. To provide morphological evidence that these functions could be mediated via the basal forebrain, we performed correlated light and electron microscopic double-immunolabeling experiments using antibodies against phenylethanolamine N-methyltransferase (PNMT) and choline acetyltransferase, the synthesizing enzymes for adrenaline and acetylcholine, respectively. Most adrenergic/cholinergic appositions were located in the horizontal limb of diagonal band of Broca, within the substantia innominata, and in a narrow band bordering the substantia innominata and the globus pallidus. Quantitative analysis indicated that cholinergic neurons of the substantia innominata receive significantly higher numbers of adrenergic appositions than cholinergic cells in the rest of the basal forebrain. In the majority of cases, the ultrastructural analysis revealed axodendritic asymmetric synapses. By comparing the number and distribution of dopamine beta-hydroxylase (DBH)/cholinergic appositions, described earlier, with those of PNMT/cholinergic interactions in the basal forebrain, it can be concluded that a significant proportion of putative DBH/cholinergic contacts may represent adrenergic input. Our results support the hypothesis that the adrenergic/cholinergic link in the basal forebrain may represent a critical component of a central network coordinating autonomic regulation with cortical activation.     

Neurotransmitters contained in the efferents of the striatum

The transmitters contained in the efferent projections of the striatum were studied by producing two types of lesions: coronal hemitransections just anterior to the globus pallidus, and semi-circular knife cuts that isolated a considerable portion of the globus pallidus from the striatum to produce 'GP islands'. The levels of substance P and Met-enkephalin in the globus pallidus, entopeduncular nucleus and substantia nigra were measured after these lesions. For comparison, the effect of these lesions on glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) in some of these projection areas of the striatum was assessed. Both lesions caused similar reductions in substance P levels in each of the three striatal projection areas. In contrast, hemitransections reduced Met-enkephalin levels only in the globus pallidus. Both lesions reduced pallidal and entopeduncular GAD activity while nigral GAD activity was reduced only by the hemitransections. CAT activity was reduced in the globus pallidus by both lesions but was unaltered in the entopeduncular nucleus. However, additional experiments ruled out the existence of a striato-pallidal cholinergic projection. GAD activity and Met-enkephalin levels were significantly increased in the striatum anterior to the lesions. In contrast, CAT activity and substance P levels did not change in this region. The results support and broaden emerging view of the organization of the neurons containing the various transmitter candidates of the efferent projections of the striatum.     

Third group of neostriatofugal neurons: neurokinin B-producing neurons that send axons predominantly to the substantia innominata

Neostriatal neurons that produce neurokinin B were investigated immunocytochemically in the rat brain with an antibody against the C-terminal portion of the precursor prepropeptide of neurokinin B, preprotachykinin B (PPTB). PPTB-immunoreactive neurons were scattered throughout the neostriatum and constituted 5.1% of neostriatal neurons. They were immunopositive for projection neuron markers, such as precursor peptides of substance P, enkephalins, and dynorphins, but negative for intrinsic neuron markers, suggesting that PPTB was expressed in neostriatal projection neurons. However, PPTB-immunoreactive neurons were immunonegative for dopamine- and cyclic AMP-regulated phosphoprotein, which is known to be produced by striatopallidal and striatonigral neurons. Furthermore, almost no PPTB-immunoreactive axon terminals were observed in the substantia nigra or globus pallidus. The authors then made large kainic acid lesions in the neostriatum to reveal the target areas of PPTB-producing neurons and observed a decrease in PPTB-immunoreactive fibers in the sublenticular portion of the substantia innominata and, to much lesser extent, in the bed nucleus of the stria terminalis and central nucleus of the amygdala. After injection of wheat germ agglutinin into the substantia innominata, PPTB immunoreactivity was detected in many retrogradely labeled neostriatal neurons. In contrast, no PPTB immunoreactivity was observed in striatonigral or striatopallidal neurons after injection of retrograde tracers into the substantia nigra or globus pallidus. Thus, neurokinin B-producing neostriatal neurons were considered to send projection fibers predominantly to the substantia innominata. Furthermore, PPTB-immunoreactive axonal swellings were closely apposed to neurokinin B receptor-immunoreactive dendrites in the substantia innominata. Overall, the present results indicate that the rat brain possesses a chemically and hodologically unique neostriatofugal pathway in addition to the direct and indirect pathways.     

Topographic organization of the basal forebrain projections to the perirhinal,postrhinal, and entorhinal cortex in rats

Previous studies have shown that the basal forebrain (BF) modulates cortical activation via its projections to the entire cortical mantle. However, the organization of these projections is only partially understood or, for certain areas, unknown. In this study, we examined the topographic organization of cholinergic and noncholinergic projections from the BF to the perirhinal, postrhinal, and entorhinal cortex by using retrograde tracing combined with choline acetyltransferase (ChAT) immunohistochemistry in rats. The perirhinal and postrhinal cortex receives major cholinergic and noncholinergic input from the caudal BF, including the caudal globus pallidus and substantia innominata and moderate input from the horizontal limb of the diagonal band, whereas the entorhinal cortex receives major input from the rostral BF, including the medial septum and the vertical and horizontal limbs of the diagonal band. In the perirhinal cases, cholinergic projection neurons are distributed more caudally in the caudal globus pallidus than noncholinergic projection neurons. Compared with the perirhinal cases, the distribution of cholinergic and noncholinergic neurons projecting to the postrhinal cortex shifts slightly caudally in the caudal globus pallidus. The distribution of cholinergic and noncholinergic neurons projecting to the lateral entorhinal cortex extends more caudally in the BF than to the medial entorhinal cortex. The ratio of ChAT‐positive projection neurons to total projection neurons is higher in the perirhinal/postrhinal cases (26–48%) than in the entorhinal cases (13–30%). These results indicate that the organization of cholinergic and noncholinergic projections from the BF to the parahippocampal cortex is more complex than previously described. J. Comp. Neurol. 524:2503–2515, 2016. © 2016 Wiley Periodicals, Inc.     

Topographic organization of the ventral striatal efferent projections in the rhesus monkey: An anterograde tracing study

The ventral striatum is considered to be that portion of the striatum associated with the limbic system by virtue of its afferent connections from allocortical and mesolimbic areas as well as from the amygdala. The efferent projections from this striatal region in the primate were traced by using 3H aminoacids and Phaseolus vulgaris-leucoagglutinin (PHA-L). Particular attention was paid to the topographic organization of terminal fields in the globus pallidus and substantia nigra, the projections to non-extrapyramidal areas, the relationship between projections from the nucleus accumbens and the other parts of the ventral striatum, and the comparison between ventral and dorsal striatal projections. This study demonstrates that in monkeys a circumscribed region of the globus pallidus receives topographically organized efferent fibers from the ventral striatum. The ventral striatal fibers terminate in the ventral pallidum, the subcommissural part of the globus pallidus, the rostral pole of the external segment, and the rostromedial portion of the internal segment. The more central and caudal portions of the globus pallidus do not receive this input. This striatal output appears to remain segregated from the dorsal striatal efferent projections to pallidal structures. Fibers from the ventral striatum projecting to the substantia nigra are not as confined to a specific region as those projecting to the globus pallidus. Although the densest terminal fields occur in the medial portion, numerous fibers also extend laterally to innervate the dorsal stratum of dopaminergic neurons of the substantia nigra and the retrorubral area. Furthermore, they project throughout the rostral-caudal extent of the substantia nigra. Projections from the medial part of the ventral striatum reach the more caudally located pedunculopontine tegmental nucleus. Thus unlike the above described terminals in the globus pallidus, the ventral striatum project widely throughout the substantia nigra, a fact that indicates that they may contribute to the integration between limbic and other output systems of the striatum. Finally, the ventral striatum projects to non-extrapyramidal regions including the bed nucleus of the stria terminals, the nucleus basalis magnocellularis, the lateral hypothalamus, and the medial thalamus.     

Topography of the magnocellular basal forebrain system in human brain

In primates, the large neurons in the nucleus basalis of Meynert (nbM), nucleus of the diagonal band of Broca (dbB), and medial septum are part of a cholinergic system with direct projections to amygdala, hippocampus, and cortex. Recent evidence indicates that neurons of this system selectively degenerate in individuals with Alzheimer's disease (AD) and suggests that degeneration of these cells contributes to the loss of presynaptic cortical cholinergic markers which occurs in these patients. The present report describes the topographical distribution of these large intensely basophilic, basal forebrain neurons in human brain. Rostrally, neurons of this magnocellular system are present in the medial septum and the dorsal and ventral parts of the nucleus of the dbB. The largest number occur in the nbM, which is situated in the substantia innominata below the globus pallidus. Caudally, large nbM-type neurons are found along the ventral and lateral edges of the globus pallidus. Neurons of this type are also encountered in the white matter below the putamen and nucleus accumbens, at the edges of the anterio commissure, in the white matter laminae of the globus pallidus and within and at the medial edge of the genu of the interal capsule. Directions for dissection of this system in human brain are given in an Appendix.     

The distribution and origin of glutamate decarboxylase and choline acetyltransferase in ventral pallidum and other basal forebrain regions.

The distribution of choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD), and the histochemical reaction for acetylcholinesterase have been studied in the basal forebrain and globus pallidus of unoperated rats and in rats with an electrolytic lesion of the nucleus accumbens. ChAT was highly concentrated in the substriatal region, the neostriatum and the lateral part of the rostral substantia innominata. The strongest intensity of staining for acetylcholinesterase was found in the substriatal grey and the neostriatum. Very high GAD activity was found in the substantia innominata, being even slightly higher than that in the pars reticulata of the substantia nigra. The lateral preoptic area, the bed nucleus of the stria terminalis and the globus pallidus also showed high activity of GAD. After lesions of the nucleus accumbens the activity of GAD decreased significantly in the substantia innominata and in a restricted part of the rostroventral globus pallidus, but not in the other regions studied. ChAT activity and acetylcholinesterase staining were unaffected in all regions. The results indicate that a dense GABAergic projection originates in the nucleus accumbens and terminates in the rostral substantia innominata and rostroventral part of the globus pallidus. The study gives neurochemical support to the suggestion that nucleus accumbens may be regarded as a ventral part of the neostriatum and that the rostral substantia innominata may be regarded as a ventral part of the globus pallidus.     

Parvalbumin-containing neurons in the basal forebrain receive direct input from the substantia nigra-ventral tegmental area

By means of anterograde tracing of Phaseolus vulgaris-leucoagglutinin (PHA-L) it was determined if parvalbumin-immunoreactive neurons in the basal forebrain receive a direct synaptic input from the A9–A10 dopaminergic nuclei of the substantia nigra and ventral tegmental area. Forebrain sections were processed for immunocytochemical detection of PHA-L and parvalbumin (PV) at light and electron microscopic levels. At the ultrastructural level, PHA-L-labeled terminals were found to establish synaptic contacts with PV-immunoreactive neuronal somata in the ventromedial globus pallidus, the ventral pallidum, the internal capsule, and the substantia innominata. PV-containing neurons in pallidal and adjacent basal forebrain territories are thus directly targeted by presumably A9–A10 dopaminergic neurons and represent a novel aspect of midbrain dopaminergic control of basal forebrain neuronal activity.     

The distribution and origin of glutamate decar☐ylase and choline acetyltransferase in ventral pallidum and other basal forebrain regions

The distribution of choline acetyltransferase (ChAT) and glutamate decar☐ylase (GAD), and the histochemical reaction for acetylcholinesterase have been studied in the basal forebrain and globus pallidus of unoperated rats and in rats with an electrolytic lesion of the nucleus accumbens. ChAT was highly concentrated in the substriatal region, the neostriatum and the lateral part of the rostral substantia innominata. The strongest intensity of staining for acetylcholinesterase was found in the substriatal grey and the neostriatum. Very high GAD activity was found in the substantia innominata, being even slightly higher than that in the pars reticulata of the substantia nigra. The lateral preoptic area, the bed nucleus of the stria terminalis and the globus pallidus also showed high activity of GAD. After lesions of the nucleus accumbens the activity of GAD decreased significantly in the substantia innominata and in a restricted part of the rostroventral globus pallidus, but not in the other regions studied. ChAT activity and acetylcholinesterase staining were unaffected in all regions.The results indicate that a dense GABAergic projection originates in the nucleus accumbens and terminates in the rostral substantia innominata and rostroventral part of the globus pallidus. The study gives neurochemical support to the suggestion that nucleus accumbens may be regarded as a ventral part of the neostriatum and that the rostral substantia innominata may be regarded as a ventral part of the glubos pallidus.     

The pallidointralaminar and pallidonigral projections in primate as studied by retrograde double-labeling method

The cellular origin and degree of collateralization of the pallidointralaminar and pallidonigral projections in squirrel monkey (Saimiri sciureus) were studied using Evans blue (EB) and a mixture of DAPI-Primuline (DP) as fluorescent retrograde tracers. In a first series of experiments EB was injected into the VA/VL thalamic nuclei whereas DP was delivered into the CM/Pf complex. After these injections numerous EB-labeled cells were scattered throughout the central 'motor' zone of the internal segment of the globus pallidus (GPi), compared to a smaller number of DP-positive neurons forming two small but distinct clusters in central GPi. The majority of the neurons within these two clusters were double-labeled. In addition, EB-labeled cells were disclosed in the lateral two-thirds of substantia nigra pars reticulata (SNr), whereas DP-positive neurons occurred in a wide variety of structures including the nucleus reticularis thalami, the SNr, the periaqueductal gray, the superior colliculus, the midbrain raphe nuclei, the pedunculopontine nucleus (TPP) area (bilaterally), and the locus coeruleus. In a second series of experiments, EB was injected into the CM/Pf complex whereas DP was delivered into the TPP area of the midbrain tegmentum. After these injections two small clusters of EB-labeled cells and a larger number of more uniformly distributed DP-positive cells occurred in the core of GPi. The cell clusters were similar in size and location to those observed after VA/VL-CM/Pf injection, but contained only a minority of double-labeled neurons. The distribution of non-pallidal cells projecting to CM/Pf complex was similar to that reported above, whereas retrogradely labeled cells resulting from TPP injection were disclosed in the paraventricular hypothalamic nucleus, the central amygdaloid nucleus, the preoptico-hypothalamic complex, the lateral habenula, the ventral tegmental area, and the SNr where some double-labeled cells were present. In a third series of experiments DP alone was injected into the entire substantia nigra (SN), involving both pars compacta and pars reticulata. The SN injection produced retrograde cell labeling in numerous structures such as the striatum, the rostral intralaminar nuclei, the subthalamic nucleus, the TPP area (bilaterally), the dorsal raphe nucleus and the locus coeruleus. At pallidal levels, a moderate number of DP-labeled cells occurred within the dorsal half of the external segment of the globus pallidus (GPe), whereas the GPi was virtually devoid of labeled neurons. The GPi appeared nevertheless surrounded ventromedially by numerous large-sized DP-positive cells belonging to the substantia innominata.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination acquisition, performance and reversal in the rat

Rats received infusions of ibotenic acid into the substantia innominata, in the region of the nucleus basalis of Meynert (nbM), before and after training on simple (simultaneous) and conditional visual discriminations. The ibotenate infusions reduced cortical choline acetyltransferase (ChAT) levels by about 20%, destroyed many ChAT-immunoreactive neurons in the nbM, but also caused the loss of many neurons in the substantia innominata and adjacent areas. These lesions did not impair the acquisition and performance of a simple visual discrimination, but did impair reversal of the discrimination and the performance of a conditional visual discrimination. However, the degree of impairment was unrelated to the degree of cortical ChAT loss. Ibotenic acid lesions to the dorsal globus pallidus also impaired reversal of discrimination but left acquisition and performance unaffected. Striatal dopamine depletion produced by 6-hydroxydopamine (6-OHDA) infusions into the mid-ventral caudate nucleus impaired performance of the simultaneous visual discrimination. Cortical noradrenaline depletion produced by 6-OHDA lesions of the dorsal noradrenergic bundle either alone or in combination with ibotenic acid lesions of the substantia innominata had no effect on acquisition of the discrimination. It is concluded that ibotenic acid lesions of the substantia innominata or to the dorsal globus pallidus affect learning and performance of conditional visual discrimination performance and impair reversal learning without affecting the capacity to discriminate visual events. These results are compared to those following cortical noradrenaline depletion or striatal dopamine loss.