Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study.

The ascending projections of the locus coeruleus were studied using an autoradiographic method. The major projection of locus coeruleus neurons ascends in a dorsal pathway traversing the midbrain tegmentum in a position ventrolateral to the periaqueductal gray. At the caudal diencephalon the locus coeruleus axons descend to enter the medial forebrain bundle at a caudal tuberal hypothalamic level. They are jointed in the medial forebrain bundle by a much smaller locus coeruleus projection which takes a ventral course through the midbrain tegmentum and enters the medial forebrain bundle via the mammillary peduncle and ventral tegmental area. Terminal projections are evident in the midbrain to the periaqueductal gray, tegmentum and raphe nuclei. There are widespread projections to the dorsal thalamus. The heaviest of these are to the intralaminar nuclei, the anteroventral and anteromedial nuclei, the dorsal lateral geniculate and the paraventricular nucleus. In the hypothalamus the largest projections are to the lateral hypothalamic area, periventricular nucleus, supraoptic nucleus and paraventricular nucleus. As the locus coeruleus projection ascends in the medial forebrain bundle, fibers leave it to traverse the lateral hypothalamus and zona incerta and enter the internal capsule, the ventral amygdaloid bundle and ansa peduncularis. These appear to terminate in the amygdaloid complex and, via the external capsule, in the lateral and dorsal neocortex. At the level of the septum 4 projections are evident. One group of fibers enters the stria medullaris to terminate in the paraventricular nucleus and habenular nuclei. A second group joins the stria terminalis to terminate in the anygdaloid complex. The third group turns into the diagonal band and medial septum; some fibers terminate in the septal nuclei and others continue into the fornix to termimate in hippocampus. A large component continues around the corpus callosum into the cingulum to terminate in the cingulate and adjacent neocortex, the subiculum and hippocampus. The remaining fibers continue rostrally in the medial forebrain bundle to terminate in olfactory forebrain and frontal neocortex. Commissural projections arise at 4 locations. The first decussation occurs in the dorsal tegmentum just below the central gray rostral to the locus coeruleus. The crossing fibers enter the contralateral dorsal bundle. A second group of fibers leaves the ipsilateral dorsal pathway, crosses in the posterior commissure and enters the contralateral dorsal pathway at the level. The third commissural projection arises more rostrally and crosses in the dorsal supraoptic commissure to enter the contralateral medial forebrain bundle. The fourth commissural projection is through the anterior commissure. The termination of the contralateral projection appears similar to that of the ipsilateral projection.     

Cholinergic and catecholaminergic afferents to the olfactory bulb in the hamster: a neuroanatomical, biochemical, and histochemical investigation

A series of neuroanatomical, biochemical, and histochemical studies have been conducted to determine the sources of cholinergic afferents to the main olfactory bulb (MOB) in the hamster. Following horseradish peroxidase (HRP) injections that are restricted to the MOB, retrograde neuronal labeling is observed bilaterally in the anterior olfactory nucleus, locus coeruleus, and raphe nuclei, and ipsilaterally in the ventral hippocampal rudiment, dorsal peduncular cortex, piriform cortex, nucleus of the lateral olfactory tract, anterior pole of the medial septal area and vertical limb of the diagonal band, nucleus of the horizontal limb of the diagonal band (HDB), and hypothalamus. Spread of HRP into the accessory olfactory bulb results in additional neuronal labeling ipsilaterally in the bed nucleus of the accessory olfactory tract, medial amygdaloid nucleus, and bed nucleus of the stria terminalis, and bilaterally in the posteromedial cortical amygdaloid nucleus. Retrograde tracing studies also have been conducted in cases with lesions in the basal forebrain or hypothalamus to assess the extent to which such lesions interrupt fibers of passage from other sources of centrifugal afferents, and the effects of such lesions on choline acetyltransferase (CAT) activity and catecholamine content in the MOB and on acetylcholinesterase (AChE) activity in the forebrain have been evaluated. Lesions in the basal forebrain reduce or eliminate CAT and AChE activity in the MOB in direct relationship to the extent of damage to the HDB. Norepinephrine (NE) content in the MOB also is reduced by basal forebrain lesions, but in relationship to damage of the medial forebrain bundle (MFB). The hypothalamic lesions have no effect on AChE activity in the forebrain or on CAT activity in the MOB, but they eliminate retrograde labeling in the locus coeruleus and raphe nuclei and reduce the NE content of the MOB to undetectable levels. The dopamine content of the MOB is not reduced by any of the lesions. Anterograde tracing studies have been conducted to compare the rostral projection patterns of the HDB with the distribution of AChE activity. Most of the rostrally directed axons travel in association with the MFB. A small component of axons travels in association with the lateral olfactory tract. Within the MOB, the axons terminate predominantly in the glomerular layer and in the vicinity of the internal plexiform layer. The projection and termination patterns of the HDB correspond well with the distribution of AChE activity. These various results indicate that the HDB is the major source of cholinergic afferents to the MOB.     

The adrenergic innervation of the rat thalamus as revealed by the glyoxylic acid fluorescence method

The adrenergic innervation of the thalamus, epithalamus, metathalamus, and subthalamus in the rat has been investigated by means of the recently introduced glyoxylic acid fluorescence method. Many areas of the thalamus and adjoining regions, that appear sparsely innervated by catecholamine (CA) fibers in specimens processed according to the standard Falck-Hillarp formaldehyde method, were found to be richly supplied with such fibres in the glyoxylic acid-treated specimens. Moreover, the glyoxylic acid method allows the tracing of the CA axons from the cell bodies up to the terminals, and in combination with stereotaxic lesions the following CA systems to the thalamus could be established:

• 1 The locus coeruleus system. Most of these axons ascend in the so-called dorsal tegmental bundle through the mesencephalon and the zona incerta into the medial forebrain bundle. From this bundle branches were traced along several routes, giving rise to extensive terminal systems in many thalamic, metathalamic and pretectal areas, most notably the anterior, ventral and lateral nuclear complexes, and the medial and lateral geniculate bodies.
• 2 The dorsal periventricular bundle, which constitutes a previously not described adrenergic component of the dorsal longitudinal fasciculus. This system originates in cell bodies (defined as the A11 cell group) in the dorsal raphe region, the central gray of the mesencephalon, and in the periventricular gray of the caudal thalamus. The axons ascend within the dorsal longitudinal fasciculus and give rise to a thalamic and hypothalamic periventricular system, projecting to medial and midline thalamic, epithalamic and pretectal regions.
• 3 Part of the terminals in the paraventricular thalamic nucleus was identified with a non-locus projection from cell bodies in the pontine or medullary reticular formation.
• 4 A system of delicate, probably dopamine-containing axons was revealed in the caudal thalamus, the zona incerta and the dorsal and anterior hypothalamus. This system probably originates in the dopamine cell bodies of the diencephalic A11 and A13 cell groups, forming a hitherto unknown intradiencephalic dopaminergic system.

The adrenergic afferent systems to the thalamus can, to a large extent, be regarded as adrenergic components of known ascending reticular projections. The information on the adrenergic systems obtained with the glyoxylic acid method revealed new features of the organization of the thalamic projections from the brain stem reticular formation.     

Organization of amygdaloid projections to brainstem dopaminergic, noradrenergic, and adrenergic cell groups in the rat.

The distribution of amygdaloid axons in the various brainstem dopaminergic, noradrenergic, and adrenergic cell groups was examined. This was accomplished by means of the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing technique combined with glucose-oxidase immunocytochemistry to catecholamine markers (i.e., tyrosine hydroxylase, dopamine beta hydroxylase, and phenylethanolamine N-methyltransferase). Injections of PHA-L in the medial part of the central amygdaloid nucleus resulted in axonal and terminal labeling in most catecholamine cell groups in the brainstem. Amygdaloid terminals appeared to contract catecholaminergic cells in several brainstem regions. The most heavily innervated catecholaminergic cells were the A9 (lateral) and A8 dopaminergic cell groups and the C2/A2 adrenergic/noradrenergic cell groups in the nucleus of the solitary tract. The medial part of the A9 and adjacent A10 dopaminergic cell groups was moderately innervated. A moderate innervation by amygdaloid terminals was observed on rostral locus coeruleus noradrenergic cells (A6 rostral) and adrenergic cells of the rostral ventrolateral medulla (C1). Noradrenergic cells of the A5, main body of the locus coeruleus (A6), A7, and subcoeruleus were sparsely innervated. Amygdaloid axons were not observed on noradrenergic neurons of the A4 cell group, area postrema, and A1 cells of the ventrolateral medulla. The results demonstrate that the amygdala primarily innervates the dopaminergic cells of midbrain (i.e., A8 and lateral A9 cells) and the adrenergic cells (C2) and noradrenergic (A2) cells in the nucleus of the solitary tract. The possible functional significance of amygdaloid innervation of catecholaminergic cells is discussed.     

Serotonin neurons of the midbrain raphe: ascending projections.

The ascending projections of serotonin neurons of the midbrain raphe were analyzed in the rat using the autoradiographic tracing method. Axons of raphe serotonin neurons ascend in the ventral tegmental area and enter the medial forebrain bundle. A number of fibers leave the major group to ascend along the fasciculus retroflexus. Some fibers enter the habenula but the majority turn rostrally in the internal medullary lamina of the thalamus to innervate dorsal thalamus. Two additional large projections leave the medial forebrain bundle in the hypothalamus; the ansa peduncularis-ventral amygdaloid bundle system turns laterally through the internal capsule into the striatal complex, amygdala and the external capsule to reach lateral and posterior cortex, and another system of fibers turns medially to innervate medial hypothalamus and median eminence and form a contrelateral projection via the supraoptic commissures. Rostrally the major group in the medial forebrain bundle divides into several components: fibers entering the stria medullaris to terminate in thalamus; fibers entering the stria terminalis to terminate in the amygdala; fibers traversing the fornix to the hippocampus; fibers running through septum to enter the cingulum and terminate in dorsal and medial cortex and in hippocampus; fibers entering the external capsule to innervate rostral and lateral cortex; and fibers continuing forward in the medial olfactory stria to terminate in the anterior olfactory nucleus and olfactory bulb.     

Olfactory relationships of the telencephalon and diencephalon in the rabbit. III. The ipsilateral centrifugal fibers to the olfactory bulbar and retrobulbar formations.

The axoplasmic retrograde transport of horseradish peroxidase (HRP) from axon terminals to their parent cell bodies and histochemical fluorescence microscopy have been used to study the ipsilateral centrifugal fibers to the olfactory bulbs and anterior olfactory nucleus in the rabbit. Focal injections of peroxidase were placed unilaterally into the main or accessory olfactory bulb or into the anterior olfactory nucleus. In animals with injected HRP confined within the main bulb, perikarya retrogradely labeled with the protein in the ipsilateral forebrain were observed in the anterior prepyriform cortex horizontal limb of the nucleus of the diagonal band, and far lateral preoptic and rostral lateral hypothalamic areas. Brain stem cell groups that contained HRP-positive somata include the locus coeruleus and midbrain dorsal raphe nucleus. Except for the prepyriform cortex, the basal forebrain structures with labeled perikarya correlate well with locations of cell bodies containing acetylcholinesterase and choline acetyltransferase. These somata may represent a cholinergic afferent system to the main olfactory bulb. Peroxidase-labeled cell bodies in the locus coeruleus and midbrain raphe are indicative of noradrenergic and serotonergic innervations respectively of the olfactory bulb. In rabbits in which peroxidase was injected or diffused into the accessory olfactory bulb and anterior alfactory nucleus, HRP-positive somata were identified in the prepyriform cortex bilaterally, the horizontal limb of the diagonal band nucleus, lateral hypothalamic region, nucleus of the lateral olfactory tract, corticomedial complex of the amygdala, mitral and tufted cell layers of the ipsilateral main olfactory bulb, locus coeruleus, and the midbrain raphe. Evidence for centrifugal fibers to the accessory olfactory bulb from the corticomedial complex of the amygdala, locus coeruleus, and possibly the nucleus of the lateral olfactory tract and midbrain raphe is discussed. A similar distribution of labeled perikarya in the forebrain and brain stem was seen in rats in which peroxidase injected into the main olfactory bulb had spread into the accessory bulb and anterior olfactory nucleus. Histochemical fluorescence microscopy of the main and accessory olfactory bulbs in the rabbit and rat revealed fine caliber, green fluorescent fibers and varicosities predominantly in the granule cell layer and less so among cells in the glomerular layer. In sections through the root of the main olfactory bulb, a similar fluorescence was seen in the deep half of the plexiform layer of the pars externa of the anterior alfactory nucleus. These fluorescent fibers likely represent the noradrenergic innervation of the olfactory bulbar and retrobulbar formations. A fluorescent yellow hue was observed in the glomerular layer of the main bulb and may signify a serotonergic innervation of this lamina...     

Efferents from medial basal forebrain and hypothalamus in the rat. I. An autoradiographic study of the medial preoptic area.

Efferent projections from the medial and periventricular preoptic area, bed nucleus of the stria terminalis and nuclei of the diagonal band were traced using tritiated amino acid autoradiography in albino rats. Medial and periventricular preoptic area efferents were not restricted to short-axon projections. Ascending projections from the medial preoptic area (mPOA) were traced through the diagonal band into the septum. Descending mPOA axons coursed in the medial parts of the medial forebrain bundle. Projections to most hypothalamic nuclei, including the arcuate nucleus and median eminence, were observed. In the midbrain, mPOA efferents were distributed in the central grey, raphe nuclei, ventral tegmental area and reticular formation. Projections from the mPOA were also observed to the amygdala through the stria terminalis, to the lateral habenula through the stria medullaris, and to the periventricular thalamus. Axons of the most medial and periventricular preoptic area (pvPOA) neurons had a distribution similar to more lateral mPOA neurons but their longest-axoned projections were weaker. The pvPOA did not send axons through the stria medullaris but did project more heavily than the more lateral mPOA to the arcuate nucleus and median eminence. Projections from the bed nucleus of the stria terminalis (nST) were in most respects similar to those from the medial preoptic area, with the major addition of a projection to the accessory olfactory bulb. The nuclei of the diagonal band of Broca (nDBB) gave a different pattern of projections than mPOA or nST, projecting, for instance, to the medial septum and hippocampus. Descending nDBB efferents ran in the ventral portion of the medial forebrain bundle. Among hypothalamic cell groups, only the medial mammillary nuclei received nDBB projections. nDBB efferents also distributed in the medial and lateral habenular nuclei and the mediodorsal thalamic nucleus.     

Distribution of thyrotropin-releasing hormone (TRH) immunoreactivity in the brain of the zebrafish (Danio rerio)

The distribution of thyrotropin-releasing hormone (TRH) in the brain of the adult zebrafish was studied with immunohistochemical techniques. In the telencephalon, abundant TRH-immunoreactive (TRHir) neurons were observed in the central, ventral, and supra- and postcommissural regions of the ventral telencephalic area. In the diencephalon, TRHir neurons were observed in the anterior parvocellular preoptic nucleus, the suprachiasmatic nucleus, the lateral hypothalamic nucleus, the rostral parts of the anterior tuberal nucleus and torus lateralis, and the posterior tuberal nucleus. Some TRHir neurons were also observed in the central posterior thalamic nucleus and in the habenula. The mesencephalon contained TRHir cells in the rostrodorsal tegmentum, the Edinger-Westphal nucleus, the torus semicircularis, and the nucleus of the lateral lemniscus. Further TRHir neurons were observed in the interpeduncular nucleus. In the rhombencephalon, TRHir cells were observed in the nucleus isthmi and the locus coeruleus, rostrally, and in the vagal lobe and vagal motor nucleus, caudally. In the forebrain, TRHir fibers were abundant in several regions, including the medial and caudodorsal parts of the dorsal telencephalic area, the ventral and commissural parts of the ventral telencephalic area, the preoptic area, the posterior tubercle, the anterior tuberal nucleus, and the posterior hypothalamic lobe. The dorsal thalamus exhibited moderate TRHir innervation. In the mesencephalon, the optic tectum received a rich TRHir innervation between the periventricular gray zone and the stratum griseum centrale. A conspicuous TRHir longitudinal tract traversed the tegmentum and extended to the rhombencephalon. The medial and lateral mesencephalic reticular areas and the interpeduncular nucleus were richly innervated by TRHir fibers. In the rhombencephalon, the secondary gustatory nucleus received abundant TRHir fibers. TRHir fibers moderately innervated the ventrolateral and ventromedial reticular area and richly innervated the vagal lobe and Cajal's commissural nucleus. Some TRHir fibers coursed in the lateral funiculus of the spinal cord. Some TRHir amacrine cells were observed in the retina. The wide distribution of TRHir neurons and fibers observed in the zebrafish brain suggests that TRH plays different roles. These results in the adult zebrafish reveal a number of differences with respect to the TRHir systems reported in other adult teleosts but were similar to those found during late developmental stages of trout (Díaz et al., 2001).     

Monoamine distribution in primate brain V. Monoaminergic nuclei: Anatomy,pathways and local organization

The noradrenergic, dopaminergic, and serotonergic cell groups of the brain stem and caudal diencephalon, and their projections, were examined in neonatal and adult squirrel monkeys, rhesus monkeys, and stump-tail monkeys utilizing the Falck-Hillarp formaldehyde condensation reaction. The axonal pathways fluoresced in neonatal monkeys and permitted direct visualization of the major bundles. Cell groups in the ventral and dorsal tegmentum of the medulla and pons (A1, A2, A3, A7) gave rise to a ventral ascending catecholamine pathway which coursed through the ventral tegmentum of the brain stem. The locus coeruleus (A4, A6) gave rise to a dorsal ascending catecholamine pathway which coursed through the medial region of the tegmentum above the ventral pathway. Prominent catecholamine cell bodies (Acg) in the central gray of the midbrain, rostral to the locus coeruleus, gave rise to an ascending dorsal periventricular pathway which ran dorsally in the tegmentum; some fibers then rapidly coursed ventrally to join a confluence with other ascending brain stem catecholamine axonal projections. The catecholamine axons ran through the medial forebrain bundle in the lateral hypothalamus, and sent further projections into limbic forebrain and cortical structures. Dopaminergic cells of the ventral tegmental area gave rise to an ascending ventral periventricular system which coursed through the most ventromedial region of the tegmentum, entered the medial forebrain bundle, and further coursed into regions of frontal and cingulate cortex, and limbic forebrain regions. The substantia nigra and some lateral cells of the lateral ventral tegmental area sent axons through the most ventral regions of the tegmentum above, and within the substantia nigra. These axons coursed into the lateral hypothalamus adjacent to the other monoaminergic axons, and proceeded to move further lateral as they ascended rostrally. They ran through the internal capsule and projected into the caudate nucleus and putamen. A major descending periventricular catecholamine system was found in the dorsal and medial region of the tegmentum of the lower brain stem, projecting into the medulla and spinal cord. Only scattered fluorescent axons were found descending to the spinal cord through the ventral tegmentum. Other catecholamine cell groups were noted in one or more primate species; they were found within the solitary tract (i.e. group Ast), and directly beneath the aqueduct (i.e. group Aaq). The hypothalamic cell groups A11–A14 were found in the caudal hypothalamus. Except for the short projection of the arcuate nucleus (A 12) to the contact zone of the median eminence, these cells gave rise to scattered axons which formed no prominent bundles visible with fluorescence histochemistry.The serotonergic cell bodies were found in the raphe nuclei of the brain stem and adjacent tegmental fields, and gave rise to both ascending and descending pathways. Nuclei raphe obscurus (B2), pallidus (B1), and magnus (B3) gave rise to dorsal and ventral descending pathways which descended to the caudal brain stem and spinal cord in a paramedian position alongside the nuclei. Nuclei raphe ponds (B5) and dorsalis (B6, B7) gave rise to a dorsal ascending serotonergic pathway, while nucleus centralis superior (B8,B9) and associated serotonergic tegmental cells gave rise to a ventral ascending serotonergic pathway. The ascending pathways coursed through the medial forebrain bundle and further projected to numerous diencephalic and telencephalic nuclei and regions.The monoamine pathways are represented in coronal, sagittal, and horizontal sections. Although differences were noted among the species examined, the general outline of the cell groups and pathways was similar. However, the primate patterns differed in several ways from comparable systems in the rat.The local organization of primate and monoaminergic nuclei demonstrated several unique characteristics. All monoaminergic nuclei demonstrated transmitter histofluorescence in primary dendrites, and sometimes in secondary or even tertiary dendrites. Some of these dendrites formed large dendrite bundles (e.g. nuclei raphe obscurus and pallidus in the caudal medulla, nuclei raphe dorsalis and centralis superior in the rostral pons and caudal mesencephalon) which possessed dendrites from both fluorescent and non-fluorescent neurons. Smaller bundles of fluorescent dendrites also were found in the locus coeruleus (coursing across the tract of the mesencephalic nucleus of V) and in the pars reticulata of substantia nigra. Further characteristics of the dendritic arborizations of the major monoaminergic nuclei are described utilizing Golgi-Cox impregnanted material. Electron microscopic observations of the locus coeruleus, substantia nigra, and raphe nuclei revealed a direct apposition of the basement membrane of some capillaries with the plasma membrane of somas and dendrites. Golgi-Cox observations revealed tanycytes on the floor of the fourth ventricle whose shafts projected into the two major raphe dendrite bundles, locus coeruleus, and the A2 region. These observations suggest that local dendritic modulation may play an important role in the regulation of neuronal excitability of some of the monoamine cell groups, and that blood-borne or CSF-borne ligands may have ready access to receptor surfaces on some monoamine cells through the unique neuronal-vascular and tanycyte shaft relationships, respectively.Electron microscopy of the medullary and dorsal raphe nuclei, locus coeruleus, substantia nigra, and ventral tegmental area revealed the presence of numerous dendro-dendritic synapses, sometimes demonstrating membrane specializations or vesicles, but not both. Each nucleus possessed a significant population (50% or more) of cells with absent or extemely sparse axo-somatic synapses. Theses somas were invested with astrocytic processes or with extended regions of the somatic membranes of oligodendroglia. Most of the synapses on these cells were axo-dendritic or dendro-dendritic. The axo-dendritic synapses terminated on both spines and parent dendrites. Some of these neurons in the raphe nuclei were tentatively identified at the ultrastructural level as serotonergic, and in locus coeruleus as catecholaminergic, utilizing x-ray analytical electron microscopic examination of chromium-tagged, glutaraldehyde-condensed monoamines. These ultrastructural observations reinforce the important role of dendrites in these major monoaminergic nuclei for the integration of afferent information from incoming axons and from dendrites of both monoaminergic and non-monoaminergic cells.     

Locus coeruleus stimulation modulates olfactory bulb evoked potentials

Field-evoked potentials from the main olfactory bulb in response to stimulation of the olfactory nerve and lateral olfactory tract were measured without and with conditioning stimulation of the locus coeruleus noradrenergic system. The locus coeruleus conditioning stimulus suppressed or inhibited the late components of the olfactory bulb potential evoked by orthodromic olfactory nerve stimulation; this inhibitory effect was suppressed by the microinjection of the alpha-adrenergic blocker prazosin into the olfactory bulb. Results indicate that noradrenergic fibers projecting from the locus coeruleus exert modulatory influences on neuronal networks underlying orthodromic evoked responses in the main olfactory bulb.     

Differential projections of the main and accessory olfactory bulb in the frog.

The central projections of the main olfactory bulb and the accessory olfactory bulb of the adult leopard frog (Rana pipiens) were reexamined, by using a horseradish peroxidase anterograde tracing method that fills axons with a continuous deposit of reaction product. The fine morphology preserved by this method allowed the terminal fields of the projection tracts to be delineated reliably, and for the first time. Herrick's amygdala has been newly subdivided into cortical and medial nuclei on the basis of cytoarchitecture, dendritic morphology, and the differential projections of the main and accessory olfactory tracts. The main olfactory bulb projects through the medial and lateral olfactory tracts to the postolfactory eminence, the rostral end of the medial cortex, the rostral end of the medial septal nucleus, the cortical amygdaloid nucleus, the nucleus of the hemispheric sulcus, and both the dorsal and ventral divisions of the lateral cortex, including its retrobulbar fringe. The lateral olfactory tract overlaps the dorsal edge of the striatal plate along the ventral border of the lateral cortex, but it is not certain whether any striatal cells are postsynaptic to the tract fibers. The lateral cortex is the largest of these territories, and receives the terminals of the main olfactory projection throughout its extent. It extends from the olfactory bulb to the posterior pole, and from the striatum to the summit of the hemisphere, where it borders the dorsal cortex. The medial and lateral olfactory tracts combine in the region of the amygdala to form a part of the stria medullaris thalami. These fibers cross in the habenular commissure and terminate in the contralateral cortical amygdaloid nucleus and periamygdaloid part of the lateral cortex. Cells projecting to the main olfactory bulb are found in the diagonal band and adjacent cell groups, but there is no evidence of an interbulbar projection arising from either the olfactory bulb proper or a putative anterior olfactory nucleus. The accessory olfactory bulb projects through the accessory olfactory tract to the medial and cortical amygdaloid nuclei. A fascicle of the tract crosses in the anterior commissure to terminate in the contralateral amygdala. While the main and accessory olfactory projections may converge in the cortical amygdaloid nucleus, the medial amygdaloid nucleus is connected exclusively with the accessory olfactory bulb.     

Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio)

Connections of the medial precommissural subpallial ventral telencephalon, i.e., dorsal (Vd, interpreted as part of striatum) and ventral (Vv, interpreted as part of septum) nuclei of area ventralis telencephali, were studied in the zebrafish (Danio rerio) using two tracer substances (DiI or biocytin). The following major afferent nuclei to Vd/Vv were identified: medial and posterior pallial zones of dorsal telencephalic area, and the subpallial supracommissural and postcommissural nuclei of the ventral telencephalic area, the olfactory bulb, dorsal entopeduncular, anterior and posterior parvocellular preoptic and suprachiasmatic nuclei, anterior, dorsal and central posterior dorsal thalamic, as well as rostrolateral nuclei, periventricular nucleus of the posterior tuberculum, posterior tuberal nucleus, various tuberal hypothalamic nuclei, dorsal tegmental nucleus, superior reticular nucleus, locus coeruleus, and superior raphe nucleus. Efferent projections of the ventral telencephalon terminate in the supracommissural nucleus of area ventralis telencephali, the posterior zone of area dorsalis telencephali, habenula, periventricular pretectum, paracommissural nucleus, posterior dorsal thalamus, preoptic region, midline posterior tuberculum (especially the area dorsal to the posterior tuberal nucleus), tuberal (midline) hypothalamus and interpeduncular nucleus. Strong reciprocal interconnections likely exist between septum and preoptic region/midline hypothalamus and between striatum and dorsal thalamus (dopaminergic) posterior tuberculum. Regarding ascending activating/modulatory systems, the pallium shares with the subpallium inputs from the (noradrenergic) locus coeruleus, and the (serotoninergic) superior raphe, while the subpallium additionally receives such inputs from the (dopaminergic) posterior tuberculum, the (putative cholinergic) superior reticular nucleus, and the (putative histaminergic) caudal hypothamalic zone.     

Catecholamin innervation of the basal forebrain. I. The septal area.

The septal area of the rat is known to receive a rich innervation by axons of catecholamine (CA) neurons. In the present study this innervatic was studied using biochemical assay of CA content and fluorescence histochemical analysis of the distribution of CA-producing axons to determine the nuclei origin of the septal CA innervation and the effects of lesions on these parameters. The autoradiographic tracing technique and the horseradish peroxidase (HRP)-retrograde transport technique also were used for this purpose. The norepinephrine (NE) content of the normal septal area is 1,162 ± 127 ng/g and the dopamine (DA) content is 522 ± 106 ng/g. Hemisection of the brainstem caudal to the locus coeruleus results in a 47% decrease in septal NE content and a unilateral locus coeruleus lesion produces a 48% decrease in septal NE content. These observations suggest that the NE innervation of the septal area arises approximately equally from the locus coeruleus and nuclei in the caudal brain stem. This is confirmed, at least in part, by the anterograde and retrograde transport studies. The DA innervation of the septal area is shown by all of the techniques employed to arise almost exclusively from cells of the ventral tegmental area. NE axons arising from the locus coeruleus distribute in the septal area to the hippocampal rudiment, the nucleus of the diagonal band, the interstitial nucleus of the stria terminalis, the medial septal nucleus, the lateral septal nucleus and the nucleus septofimbrialis. In each area the innervation is sparse to moderate in density and has the plexiform organization typical of locus coeruleus innervation. The brainstem NE innervation is very dense in the interstitial nucleus of the stria terminalis, moderately dense in the lateral septal nucleus and sparse in the nucleus of the diagonal band. The DA axons innervating the septum terminate in two distinct patterns. The first is identical to that seen in the neostriatum. Preterminal axons are very fine and non-varicose. As they reach a terminal area they branch markedly and give rise to extremely numerous, closely-packed, fine varicosities. This type of DA innervation is found in the medial part of the lateral septal nucleus in a dense band and about some scattered lateral septal nucleus neurons, in the nucleus accumbens and in the interstitial nucleus of the stria terminalis. The second pattern is for non-varicose preterminal axons to branch and terminate in pericellular baskets about lateral septal nucleus neurons or simply terminate in the lateral septal nucleus neuropil. In each case the terminal branches give off distinct varicosities which are larger than those formed in the first pattern of DA innervation. Thus, the septal area has a complex organization of CA innervation with NE axons arising from caudal brainstem nuclei and the locus coeruleus and DA axons arising from the ventral tegmental area.     

The projection field of the stria terminalis in the rat brain. An experimental study

The problem of the stria terminalis projection field has been examined by use of two versions of the cupric-silver technique as well as variations of the Fink-Heimer and Nauta-Gygax techniques applied to material fixed under different conditions using brains from very young rats surviving 30 hours to four days after production of lesions at different levels of the course of the stria terminalis and related structures. The findings are as follows:

• (1) A dorsal subventricular portion of the stria terminalis divides into retrocommissural and supracommissural contingents which together account for degenerating terminals seen in the ipsilateral bed nuclei of the stria terminalis and of the anterior commissure, and in the medial preoptic-hypothalamic junction area. The supracommissural bundle also disseminates into the laterobasal septum, nucleus accumbens, olfactory tubercle, the posterior and medial divisions of the anterior olfactory nucleus, and the granular layer of the accessory olfactory bulb. Additional fibers end in the paucicellular capsule of the ventromedial hypothalamic nucleus, also in a small lateral parvocellular tuberal nuclear area, and throughout the premammillary nuclei. A small truly commissural division of the dorsal component was traced to the contralateral cortical amygdaloid nucleus and to small clusters of medial amygdaloid cells.
• (2) A ventral juxtacapsular portion of the stria terminalis was traced to the ipsilateral strial bed nucleus, medial preoptic-hypothalamic junction area, the entire ventromedial hypothalamic nucleus, the lateral tuberal area and the premammillary nuclei. The lateralmost fibers of the dorsal strial component as well as those of the ventral component which lie lateral to the “commissural bundle” appear to terminate exclusively in the lateral portions of the bed nucleus of the stria.
• (3) A “commissural bundle” or component, after crossing the midline in the anterior commissure, ends in the bed nucleus of the posterior limb of the latter, in the olfactory tubercle, prepiriform cortex, lateral amygdaloid nucleus and the strial bed nucleus. It is thus a decussation rather than a commissure. No contribution from stria terminalis to stria medullaris could be identified.

     

Experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). II: Dorsal area and preoptic region

In this study and the accompanying article (Folgueira et al., 2004a), the fluorescent carbocyanine dye 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was used in fixed tissue to comprehensively analyze the connections of the different regions of the telencephalic lobes and the preoptic region of the rainbow trout. Here, we analyze the connections of the dorsal area (D; pallium) of the telencephalon, and the preoptic region, as well as the telencephalic connections of several structures in the diencephalon and brainstem of juvenile trout. The dorsal plus dorsolateral pallial zone of D (Dd+Dl-d) receives afferents from contralateral Dd+Dl-d, the ventral area of the telencephalon, preoptic nucleus, suprachiasmatic nucleus, medial thalamus, preglomerular complex, anterior and lateral tuberal nuclei, posterior tuberal nucleus, posterior hypothalamic lobe, superior raphe nucleus, and the rhombencephalic central gray and reticular formation, and projects to the central zone of D (Dc), medial thalamus, and some caudomedial hypothalamic regions. The medial zone of D (Dm) maintains reciprocal connections with the preglomerular complex and also receives afferents from the preoptic nucleus, suprachiasmatic nucleus, anterior tuberal nucleus, preglomerular tertiary gustatory nucleus, posterior tubercle, superior raphe nucleus, locus coeruleus, and the rhombencephalic central gray, and reticular formation. Dc receives fibers mainly from Dd+Dl-d, preoptic nucleus, preglomerular complex, and torus semicircularis and projects to several extratelencephalic centers, including the paracommissural nucleus, optic tectum, torus semicircularis, thalamus, preglomerular complex, posterior tubercle nuclei, and inferior hypothalamic lobes. The posterior zone of D (Dp) is mainly connected with the olfactory bulbs, the ventral and supracommissural nuclei of the ventral area (subpallium), the preoptic nucleus, and the preglomerular complex and projects to wide hypothalamic and posterior tubercular regions. The preoptic nucleus projects to the olfactory bulb, to most regions of the telencephalic lobes, and to several diencephalic and brainstem structures. These results reveal complex and specialized connectional patterns in the rainbow trout dorsal telencephalon and preoptic region. Most of these connections have not been described previously in salmonids. These connections indicate that the salmonid telencephalon is involved in multisensorial processing and modulation of brain activity.     

Noradrenergic innervation of the developing and mature septal area of the rat

The noradrenergic innervation of the developing and mature septal area of the rat was examined with light and electron microscopic immunocytochemistry using an antibody against dopamine-beta-hydroxylase. At birth, a small number of relatively thick noradrenergic fibers were found to innervate the lateral septum (mainly its intermediate part) and the nuclei of the vertical and horizontal limbs of the diagonal band of Broca. By postnatal day 7, a substantial increase in their density was observed. At this age some labeled fibers left the medial forebrain bundle and invaded the nucleus of the horizontal limb of the diagonal band. These fibers then ran in a ventrodorsal direction and innervated the nucleus of the vertical limb before entering the medial septum. Immunoreactive fibers were finer and more varicose than at birth. In the subsequent 2 weeks, the density of labeled fibers in the septal area was further increased. By postnatal day 21, the distribution pattern and density of the noradrenergic innervation appeared similar to the adult. In the adult, noradrenergic fibers exhibited more varicosities than in younger rats. Electron microscopic analysis revealed a low proportion (peaked at P7) of noradrenergic varicosities engaged in synaptic contacts throughout development. The overwhelming majority of these synapses were symmetrical, predominantly with small or medium-sized dendrites. The present findings provide the morphological basis for the functional interactions between noradrenergic afferents and neuronal elements in the septal area. The low proportion of synaptic contacts found in this study suggests that noradrenaline may exert its action in the septal area mainly through transmission by diffusion (volume transmission), as has been suggested for other areas of the developing and adult brain.     

Hypothalamic influences on the electrical activity of the olfactory pathway

By means of evoked potentials a direct efferent connection was found to run from the posterior hypothalamus and medial forebrain bundle to primary olfactory structures (olfactory bulb, olfactory tubercle and prepyriform cortex). The pathway from the hypothalamus to the olfactory bulb follows in the lateral olfactory tract at a conduction velocity 5–10 m/sec. The olfactory tubercle functions as a relay station for the efferent fibers from various sources, running to the olfactory bulb. In animals with electrodes chronically implanted in the olfactory structures, hypothalamic stimulation gives rise to a prolonged train of hypersynchronous bursts of activity (40–50 Hz), which resemble the arousal reaction. This response is modified by transecting the cervical sympathetic trunk. By pathways still to be defined, potentials are evoked in the olfactory bulb by stimulation of the cervical sympathetic trunk and the termination of these sympathetic fibers shows a common postsynaptic neuronal pool with axons of hypothalamic origin. Epinephrine topically applied to the olfactory mucosa induced hypersynchronous activity in olfactory structures, quite similar to that consequent to hypothalamic stimulation. These results suggest a multichanneled hypothalamic modulation of olfactory input.     

Efferents of the medial preoptic area in the guinea pig: An autoradiographic study

Medial preoptic axons were traced into the diagonal band of Broca and septum, particularly lateral septum. Other labeled fibers could be followed dorsally from medial preoptic area injections adjacent to the stria medullaris, and in the periventricular fiber system and the stria terminalis and its bed nucleus. The anterior and medial amygdaloid nuclei were labeled by fibers via the stria terminalis and others arching over the optic tract and through the substantia innominata. The lateral habenula was labeled. Labeled periventricular fibers reached the periventricular nucleus of the thalamus. Descending efferents were traced principally below the fornix and in the adjacent lateral hypothalamus to label the anterior hypothalamus, the tuberal nuclei, and median eminence. Axons of the medial preoptic area joined the medial part of the medial forebrain bundle and distributed to the reticular formation and the central gray of the midbrain and pons. A small amount of contralateral connections were described.     

Ascending connections of a thalamic auditory area in a crocodile, caiman crocodilus

Nucleus reuniens pars centralis is the major recipient of the ascending auditory lemniscus from the midbrain in the crocodile, Caiman crocodilus. Its ascending connections were studied by means of the Fink-Heimer procedure with the light microscope after anodal, stereotaxic lesions. Following unilateral destruction of nucleus reuniens pars centralis, degenerating axons assemble on the lateral aspect of the pars centralis, pass through the pars diffusa, and enter the dorsal peduncle of the lateral forebrain bundle. These fascicles travel rostrally in the lateral forebrain bundle where they remain restricted to the medial aspect of this tract. At more rostral levels, these degenerating axons turn dorsad, pass through and perhaps synapse on interposed neurons of the medial portion of the ventrolateral area, and end on cells located in the overlying dorsolateral area. This terminal field is composed of small, round, tightly packed neurons located in a medial caudal part of the dorsolateral area. This experiment together with a previous report demonstrates the existence of a specific and sharply localized auditory pathway leading from the central nucleus of the torus semicircularis by way of nucleus reuniens pars centralis to the telencephalon. The findings of this study are compared with similar research on thalamotelencephalic projections of diencephalic auditory areas in other amniotes.