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Subset of neurons characterized by the presence of NADPH-diaphorase in human substantia innominata.

The substantia innominata encompasses an area of the basal forebrain that is ventral to the lenticular nucleus and anterior commissure, medial to the claustrum and external capsule, and lateral to the hypothalamus. The nucleus basalis of Meynert consists primarily of large acetylcholinesterase (AchE)-positive neurons embedded within the substantia innominata. Damage to these neurons may be important in the pathogenesis of cortical dysfunction in Alzheimer's disease. In order to characterize other neuronal elements in the substantia innominata and their relationship to the nucleus basalis, we chose to study a biochemically distinct neuronal subset containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The substantia innominata was blocked from six normal brains obtained postmortem and fixed in neutral-buffered formalin at 4 degrees C for 48 hours. Free-floating 50-micron sections from several levels were stained for NADPH-d or AchE activities. Selected sections were double stained for NADPH-d and AchE. NADPH-d activity was present in a network of pleomorphic neurons that extended through all levels of the substantia innominata and into the striatum and amygdala. NADPH-d neurons were particularly numerous at the level of the anterior commisure and were closely associated with the cholinergic neurons of the nucleus basalis. They were not seen in the ventral pallidum, or the vertical limb of the diagonal band of Broca or in the islands of Calleja. The cell bodies of NADPH-d neurons were quite varied in shape, ranging from ovoid to fusiform, and about half the cells were bipolar. Where neuronal density was high, their dendrites formed an interlacing pattern. NADPH-d-positive fibres were seen coursing through the external capsule, hypothalamus, and amygdala. This novel set of neurons in the substantia innominata may be part of a more extensive network that interacts with the magnocellular basal forebrain system at the level of the nucleus basalis. Whether other neurotransmitters are present within these neurons and whether NADPH-d neurons are involved in Alzheimer's disease remain to be elucidated.

Aged↗

The synchronizing influence of Substantia Innominata on the thalamus of the cat.

We examined the stimulating effect of Substantia Innominata pars anterior (SIa), during the waking state, on the 'central' part of the Mediodorsal nucleus of the thalamus (MD), combining electrophysiological and anatomical techniques in restrained, undrugged, unanaesthetized cats. Thalamic MD units were recorded, after electrical stimulation of the Substantia Innominata, at 1 Hz, with a single pulse or short trains of four pulses. Responses were studied by poststimulus histograms. In about 64 of the 84 recorded MD neurones (76%), stimulation of the Substantia Innominata, during the waking state, induced a brief cell excitation, followed first by prolonged inhibition of firing and then by a strong excitatory rebound discharge; after this comes a second sequence of inhibition and excitation, of decreasing amplitude. After stimulation of the Substantia Innominata, the MD units tended to start a repetitive discharge at 4--7 Hz. To investigate the connections of Substantia Innominata cells upon the areas where MD units were recorded we injected horseradish peroxidase wheat germ agglutinin (WGA-HRP), combined with immunohistochemistry for glutamic acid decarboxylase (GAD) and choline acetyl transferase (ChAT). Of the total population of retrogradely labelled cells in the Substantia Innominata 53% were GAD positive while less than 16% were ChAT positive. The GAD positive MD-projecting cells in the Substantia Innominata were triangular to fusiform and small to medium in size. These findings indicate that GABAergic input from the Substantia Innominata may contribute to increasing the hyperpolarizing inhibitory pressure on MD cells in the 'central' part during slow wave sleep (SWS).

Animals↗

MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia.

BACKGROUND AND PURPOSE: The substantia innominata can be visualized on coronal thin-section T2-weighted MR images. The purpose of this study was to investigate the morphologic changes of the substantia innominata in normal aging by using MR imaging and to determine whether the changes in this structure on MR images were specific to Alzheimer disease (AD). METHODS: The thickness of the substantia innominata was measured on the coronal T2-weighted image obtained through the anterior commissure in 39 healthy control subjects (age range, 25-86 y; mean age, 62 y); 39 patients with AD; and 36 patients with non-AD dementia, including vascular dementia, frontotemporal dementia, and Parkinson disease with dementia. RESULTS: In the control subjects, the thickness of the substantia innominata significantly decreased with age. Compared with age-matched control subjects, both patients with AD and patients with non-AD dementia had significant atrophy of the substantia innominata. The thickness of the substantia innominata significantly correlated with scores from the Mini-Mental State Examination in patients with AD but not in patients with non-AD dementia. CONCLUSION: MR analysis reveals age-related shrinkage of the substantia innominata. Atrophy of the substantia innominata, which reflects degeneration in the nucleus basalis of Meynert, is pronounced both in patients with AD and in those with non-AD dementia. MR imaging features in this structure may not be specific to AD.

Adult↗

[Limbic seizure and ibotenic acid-induced lesions of substantia innominata in cats].

The substantia innominata (SI) contains a lot of cholinergic neurons and mainly project their fibers to the cerebral cortex and to the amygdala. Degenerative lesions were made in the bilateral SI and influences of these lesions upon kainic acid-induced limbic seizure were studied. Eleven adult cats were stereotaxically implanted and 2.5 micrograms of ibotenic acid (IBO) was injected into the bilateral SI in 6 cats (IBO group) and 1 microliter of phosphate buffer (PB) in 5 cats (PB group). All animals were given freedom at least 8 days to recover from the operation. Kainic acid microinjection was made into the left amygdala and electroclinical observation was done. In PB group, the limbic status was elicited and these seizures persisted for about 3 days after the KA injection. Seizures were subsided but interictal discharges were observed at the injected site of the amygdala. Then, limbic seizures reappeared within 10 days and a slowly progressive development of limbic seizure was observed. These seizures developed further. Occasionally, these limbic seizures successively developed and secondarily generalized seizures occurred once or twice a week. Otherwise, their clinical behaviors were normal during the interictal periods. In IBO group, the limbic status were elicited and lasted for about 3 days after the KA injection. Although interictal discharges reappeared at the injected site of the amygdala, successive development of the limbic seizure was not observed. The secondarily generalized seizure never occurred in the IBO group. Histopathological studies revealed circumscribed degenerative changes in the bilateral SI. The KA microinjection into the amygdala resulted stereotyped amygdaloid degenerative lesions in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

The afferent connections of the substantia innominata in the monkey, Macaca fascicularis.

The afferent connections of the substantia innominata and the magnocellular nuclei within it (the nucleus of the horizontal limb of the diagonal band, NHDB, and the nucleus basalis of Meynert, NBM) have been studied with anterograde and retrograde axonal tracing techniques. Prominent inputs arise in the amygdaloid complex, restricted areas of the cerebral cortex, parts of the thalamus and hypothalamus, and nuclei of the lower brainstem. Autoradiographic tracing experiments indicate that the amygdaloid fibers are distributed throughout the NHDB and the NBM, and to a lesser extent to the ventral pallidum. Relatively few fibers innervate the more medially located nucleus of the vertical limb of the diagonal band (NVDB) and the medial septal nucleus. Visualization of the amygdalofugal fibers with the tracer PHA-L (Phaseolus vulgaris leuco-agglutinin) shows that they have varicosities resembling boutons en passant along their length in the substantia innominata. Retrograde tracing experiments using WGA-HRP indicate that the cells of origin of the projection from the amygdala are concentrated in the parvicellular basal nucleus, the caudal part of the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the central nucleus. Relatively few fibers to the substantia innominata arise in the rostrodorsal part of the magnocellular basal nucleus, or in the lateral or parvicellular accessory basal nuclei. Cortical cells projecting to the substantia innominata were retrogradely labeled in the orbitofrontal cortex (including areas 11-14 and 25), the rostral insula (especially the agranular area), the rostroventral temporal cortex (including areas 35, 36, and parts of TG and TE), and the piriform and entorhinal cortices. The projections from the orbital and rostral temporal cortex were confirmed with anterograde tracers. Projections to the substantia innominata were not found from the more lateral, dorsal or caudal parts of the cerebral cortex, although fibers from temporal area TA may pass through the dendritic field of the most caudal cells of the NBM. Diencephalic cells projecting to the substantia innominata are distributed diffusely throughout the preoptic area and hypothalamus, with higher concentration in the lateral preoptic area and in the pre-, supra-, and tubero-mammillary nuclei. Cells are also found in the midline thalamic nuclei and in the region between the peripeduncular and subparafascicular nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease.

Atrophy of the substantia innominata on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, may be an in vivo marker of cholinergic damage. We attempted to investigate whether the MRI features of the substantia innominata predict response to donepezil treatment in Alzheimer's patients. The thickness of the substantia innominata was measured on the coronal T2-weighted MRI through the anterior commissure. Seventy-two patients treated with donepezil were divided into the two groups (responders and non-responders) based on changes in Mini-Mental State Examination (MMSE) scores from baseline to study endpoint. Atrophy of the substantia innominata was more pronounced in responders than non-responders. There was a significant inverse correlation between thickness of the substantia innominata and MMSE changes. MRI analysis of the substantia innominata may be a simple and practical method for the selection of possible treatment responders.

Acetylcholine↗

The substantia innominata and adjacent regions in the human brain: histochemical and biochemical observations.

The substantia innominata was investigated in the adult human brain with particular reference to the cholinergic nature of the nucleus of Meynert. Based on histochemical observations of acetylcholinesterase activity and biochemical estimations of choline acetyltransferase the relations of the Meynert nucleus to adjacent structures in the substantia innominata region were identified precisely. A new dissection procedure is described which permits combined histochemical and histological examination of anatomically complex regions of the human brain, such as the substantia innominata, to be carried out in conjunction with accurate tissue dissection for neurochemical analysis. Using this technique, various acetylcholinesterase-positive and choline acetyltransferase-containing structures are apparent in coronal sections removed from the rostrocaudal length of the substantia innominata. These include, in addition to the prominently stained, putative cholinergic neurons, acetylcholinesterase-positive tracts which contain putative cholinergic projections to the neocortex, and 'islands' of acetylcholinesterase-positive neuropil which presumably reflect a collateral or intrinsic cholinergic innervation in the area. This anatomical complexity of cholinergic structures in the substantia innominata suggests that neurochemical analysis should be conducted on microdissected as opposed to macrodissected tissue samples. Neuropathologically, the present report provides a further basis for optimising quantification of putative cholinergic perikarya. Continued systematic analysis of the nucleus of Meynert at the morphological and biochemical level should thus establish the role of this nucleus in normal brain function and in disease.

Acetylcholinesterase↗

MR anatomy of the substantia innominata and findings in Alzheimer disease: a preliminary report.

PURPOSE: To demonstrate normal MR anatomy of the substantia innominata and its changes in Alzheimer disease on MR imaging. METHODS: Using a 1.5-T superconductive MR unit, thickness of the substantia innominata was measured on coronal thin-section images obtained in 22 patients with Alzheimer disease and 14 age-matched control subjects. Comparison of these images with postmortem specimens of human brain was also performed. RESULTS: On T2-weighted images through the anterior commissure, the substantia innominata was clearly identified between the globus pallidus and the anterior perforated substance. In Alzheimer disease, thinning of the substantia innominata was more frequently observed than in the age-matched controls. CONCLUSION: Thin-section T2-weighted coronal MR images can demonstrate shrinkage of the substantia innominata, a finding that may aid in the diagnosis of Alzheimer disease.

Aged↗

Atrophy of the substantia innominata on magnetic resonance imaging predicts response to donepezil treatment in Alzheimer's disease patients.

To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer's disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy. Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months. Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found. The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata. Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders. We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD.

Aged↗

Evidence that projections from substantia innominata to zona incerta and mesencephalic locomotor region contribute to locomotor activity.

A series of anatomical, electrophysiological and behavioral experiments was carried out in the rat to investigate the possible functional significance of a recently demonstrated neural pathway from the substantia innominata of the subpallidal forebrain to the mesencephalic locomotor region. Following injections of the anterogradely transported lectin PHA into the substantia innominata labeled fibers with terminal boutons were observed in the zona incerta, dorsal to the medial part of the subthalamic nucleus, and some appeared to continue on to the pedunculopontine nucleus. Electrophysiological recordings of action potentials were made from neurons in the substantia innominata and some of these neurons were activated antidromically by single-pulse stimulation of the zona incerta and/or by single-pulse stimulation of the pedunculopontine nucleus as well. Neurons in the zona incerta responded orthodromically to stimulation of the substantia innominata. Locomotor activity was initiated by injecting picrotoxin, a GABA antagonist, unilaterally into the substantia innominata through chronic cannulae, as reported previously. This picrotoxin-initiated locomotor activity was reduced significantly when procaine (a neuronal blocker) was injected into the ipsilateral zona incerta. Injecting procaine into the contralateral zona incerta had little or no effect on the picrotoxin-initiated locomotor activity. Taken together these observations suggest the tentative working hypothesis that projections from the substantia innominata to the zona incerta as well as the pedunculopontine nucleus may contribute to the locomotor component of adaptive behaviors resulting from limbic forebrain integrative activities, an hypothesis that can now be investigated further.

Animals↗

Effects of stimulation of the substantia innominata upon attack behavior elicited from the hypothalamus in the cat.

Experiments were undertaken in order to determine the role of the substantia innominata and surrounding regions in quiet biting attack elicited from electrical stimulation of the hypothalamus in the cat. Stimulation from sites in the lateral aspect of the substantia innominata resulted in a suppression of quiet biting attack and in a constriction of the 'effective trigeminal sensory fields' established during hypothalamic attack site stimulation. Stimulation from sites situated more medially in the substantia innominata resulted in a facilitation of quiet biting attack and in an expansion of the 'effective trigeminal sensory fields'. The motor component of the jaw opening response was altered in only 50% of the cases in contrast to the consistent effects observed upon the 'effective sensory fields'. Electrical stimulation of the substantia innominata had little effect upon affective display elicited from the ventromedial hypothalamus. Stimulation from sites located in the nucleus accumbens had no effect upon hypothalamically-elicited quiet biting attack and inhibited the occurrence of affective display in 2 to 5 animals tested. These studied suggest that the substantia innominata differentially modulates quiet biting attack and accomplishes this, at least in part, through its effects upon sensory mechanisms associated with the jaw opening reflex.

Affect↗

Neuropeptide localisation in the substantia innominata and adjacent regions of the human brain.

A dense peptidergic innervation has been demonstrated in the substantia innominata region in postmortem specimens of human brain using immunocytochemical techniques. A peptidergic innervation of the nucleus of Meynert - the prominent nucleus of this area containing the cholinergic cell bodies which innervate the cerebral cortex - has been demonstrated by immunostaining with antisera against the following eight neuropeptides: somatostatin, substance P, cholecystokinin octapeptide, vasoactive intestinal polypeptide, met-enkephalin, ACTH, alpha-MSH and oxytocin. Other immunocytochemical features of the substantia innominata region include a dense band of peptide immunoreactivity beneath the medial aspect of the anterior commissure and islands of somatostatin and substance P terminal immunoreactivity in the rostral part of the substantia innominata. Somatostatin immunostained cell bodies have been located in a discrete area of the bed nucleus of the stria terminalis and in the rostral portion of the substantia innominata, nucleus accumbens and the ventral part of the putamen. The dense band of peptide immunoreactivity beneath the medial aspect of the anterior commissure consists of ribbon-like processes stained with antisera against somatostatin, substance P, cholecystokinin octapeptide, vasoactive intestinal polypeptide and met-enkephalin. Less intense immunostaining of ribbon-like elements is also present in the globus pallidus. The presence of a peptidergic innervation to the nucleus of Meynert suggests a possible important modulatory role in cortical cholinergic function.

Adrenocorticotropic Hormone↗

Suppression of amygdala-kindled seizure in cats by enhanced GABAergic transmission in the substantia innominata.

The chronological effect of intracerebral injection of GABAergic drugs, either muscimol or gabaculine, into the substantia innominata, was examined in amygdala-kindled cats. Results obtained indicate: that the substantia innominata may play a significant role in ictal linkage between a nonmotor system such as the amygdala and the motor mechanism responsible for amygdala-kindled convulsion, and that the GABA terminals in the substantia innominata exert a suppressive action toward convulsive seizure generalization of amygdala origin.

Amygdala↗

Serotonergic input to cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis in the rat.

The aim of the present study was to determine, at the light microscopic level, whether the serotonergic fibers originating from the dorsal raphe nucleus (B7), median raphe nucleus (B8) and ventral tegmentum (B9) make putative synaptic contacts with cholinergic neurons of the nucleus basalis magnocellularis and substantia innominata. For this purpose, we utilized: (i) the anterograde transport of Phaseolus vulgaris leucoagglutinin combined with choline acetyltransferase immunohistochemistry; (ii) choline acetyltransferase/tryptophan hydroxylase double immunohistochemistry; and (iii) the FluoroGold retrograde tracer technique combined with tryptophan hydroxylase immunohistochemistry. Following iontophoretic injections of Phaseolus vulgaris leucoagglutinin in the dorsal raphe nucleus, labeling was observed primarily in the ventral aspects of the nucleus basalis magnocellularis and in the intermediate region of the substantia innominata. When Phaseolus vulgaris leucoagglutinin was combined with choline acetyltransferase immunohistochemistry, a close association between the Phaseolus vulgaris leucoagglutinin-positive fibers and cholinergic neurons was observed, even though the majority of the Phaseolus vulgaris leucoagglutinin-immunoreactive terminals seemed to establish contact with non-cholinergic elements. Following Phaseolus vulgaris leucoagglutinin injection in the median raphe nucleus, very few labeled fibers with no evident close contact with nucleus basalis magnocellularis and substantia innominata cholinergic neurons were observed. After tryptophan hydroxylase/choline acetyltransferase double immunohistochemistry, a plexus of serotonergic (tryptophan hydroxylase-positive) fibers in the vicinity of choline acetyltransferase-immunoreactive neurons of the substantia innominata and nucleus basalis magnocellularis was observed, and some serotonergic terminals have been shown to come into very close contact with the cholinergic cells. Most of the tryptophan hydroxylase-immunoreactive terminals seem to establish contacts with non-cholinergic cells. Following FluoroGold injection in the nucleus basalis magnocellularis and substantia innominata, the majority of retrogradely labeled neurons was observed mainly in the ventromedial cell group of the dorsal raphe nucleus. In this area, a minority of the FluoroGold-positive neurons was tryptophan hydroxylase immunoreactive. These findings show that serotonergic terminals, identified in very close association with the cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis, derive primarily from the B7 serotonergic cell group of the dorsal raphe nucleus, and provide the neuroanatomical evidence for a direct functional interaction between these two neurotransmitter systems in the basal forebrain.

Animals↗

Substantia innominata: a notion which impedes clinical-anatomical correlations in neuropsychiatric disorders.

Comparative neuroanatomical investigations in primates and non-primates have helped disentangle the anatomy of the basal forebrain region known as the substantia innominata. The most striking aspect of this region is its subdivision into two major parts. This reflects the fundamental organizational scheme for this portion of the forebrain. According to this scheme, two major subcortical telencephalic structures, i.e. the striatopallidal complex and extended amygdala, form large diagonally oriented bands. The rostroventral extension of the pallidum accounts for a large part of the rostral subcommissural substantia innominata, while the sublenticular substantia innominata is primarily occupied by elements of the extended amygdala. Also dispersed across this region is the basal nucleus of Meynert, which is part of a more or less continuous collection of cholinergic and non-cholinergic corticopetal and thalamopetal cells, which stretches from the septum diagonal band rostrally to the caudal globus pallidus. The basal nucleus of Meynert is especially prominent in the primate, where it is sometimes inappropriately applied as a synonym for the substantia innominata, thereby tacitly ignoring the remaining components. In most mammals, the extended amygdala presents itself as a ring of neurons encircling the internal capsule and basal ganglia. The extended amygdala may be further subdivided, i.e. into the central extended amygdala (related to the central amygdaloid nucleus) and the medial extended amygdala (related to the medial amygdaloid nucleus), which generally form separate corridors both in the sublenticular region and along the supracapsular course of the stria terminalis. The extended amygdala is directly continuous with the caudomedial shell of the accumbens, and to some extent appears to merge with it. Together the accumbens shell and extended amygdala form an extensive forebrain continuum, which establishes specific neuronal circuits with the medial prefrontal-orbitofrontal cortex and medial temporal lobe. This continuum is particularly characterized by a prominent system of long intrinsic association fibers, and a variety of highly differentiated downstream projections to the hypothalamus and brainstem. The various components of the extended amygdala, together with the shell of the accumbens, are ideally structured to generate endocrine, autonomic and somatomotor aspects of emotional and motivational states. Behavioral observations support this proposition and demonstrate the relevance of these structures to a variety of functions, ranging from the various elements of the reproductive cycle to drug-seeking behavior. The neurochemical and connectional features common to the accumbens shell and the extended amygdala are especially relevant to understanding the etiology and treatment of neuropsychiatric disorders. This is discussed in general terms, and also in specific relation to the neurodevelopmental theory of schizophrenia and to the neurosurgical treatment of neuropsychiatric disorders.

Animals↗

[Participation of the substantia innominata in differential inhibition in the cat].

Elaboration of differentiation, its disturbance resulting from bilateral lesion of the substantia innominata and its subsequent restoration was studied in cats. Ablation of the substantia innominata was accompanied by disturbances of the internal inhibition. The initial level, that before the operation, was not obtained even after a long training. It is suggested that substantia innominata modulates cortical activity and its ablation prolongs the afferent synthesis.

Animals↗

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.

Animals↗

Evidence for a projection from the lateral preoptic area and substantia innominata to the 'mesencephalic locomotor region' in the rat.

A series of anatomical and electrophysiological experiments have been carried out to examine the organization of a direct projection from the substantia innominata and the lateral preoptic area of the hypothalamus, referred to collectively as the subpallidal region, to the pedunculopontine nucleus and adjacent parts of the dorsal midbrain in the adult rat. In the first series of experiments, the retrogradely transported fluorescent tracer SITS, which does not appear to be taken up by fibers-of-passage, was injected into the pedunculopontine nucleus, and the distribution of labeled neurons was plotted in the substantia innominata and lateral preoptic area, as well as in adjacent regions including the medial preoptic area, the bed nucleus of the stria terminalis and parvocellular parts of the paraventricular nucleus. Then, the anterogradely transported lectin PHA-L, which also does not appear to be taken up in effective amounts by fibers-of-passage, was injected into parts of the substantia innominata and lateral preoptic area that project directly to the pedunculopontine nucleus. These experiments demonstrated that fibers from both regions descend through the medial forebrain bundle and give rise in the pedunculopontine nucleus to a terminal field that contains many structures with the appearance of terminal boutons. They also indicated that individual fibers from the subpallidal region innervate both the pedunculopontine nucleus and adjacent parts of the central gray, and that the pathway innervates areas along the length of the medial forebrain bundle on its way to the dorsal midbrain. In a third series of experiments the retrogradely transported fluorescent tracer True Blue was injected into upper thoracic levels of the spinal cord, and it was found that the region of the pedunculopontine nucleus that receives the densest input from the subpallidal region contained many retrogradely labeled neurons on both sides of the brain. And finally, a series of electrophysiological experiments demonstrated that single-pulse stimulation of the substantia innominata and the lateral preoptic area altered the firing rate of a majority of the neurons in and around the pedunculopontine nucleus, and that excitatory and inhibitory responses occurred about equally. These results clearly suggest that the subpallidal region projects directly to the pedunculopontine nucleus and adjacent regions including the central gray and the superior colliculus.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗