The role of the medial septal nucleus in mediating adrenocortical responses to somatosensory stimulation

In view of the demonstrated involvement of the hippocampus in the mediation of adrenocortical responses following sciatic nerve stimulation, the role of the septum and the preoptic area in the transmission of this response was investigated. Changes in plasma corticosterone following ether stress and photic, acoustic, or sciatic nerve stimulation were studied in intact rats and in animals with lesions in the medial septal nucleus and the preoptic area. The response to ether stress and to photic and acoustic stimulation was normal in these animals. However, the adrenocortical response to sciatic nerve stimulation was partially reduced in the rats with lesions in the superior, but not in the inferior preoptic area, and it was completely blocked in those with medial septal lesions. Our previous and present experiments indicate that the ventral hippocampus, the fimbria, the septum, and anterior hypothalamic afferents mediate the adrenocortical response to somatosensory stimulation.     

A [C]2-Deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. III. The hippocampal formation

The regions metabolically activated in the rat brain following focal electrical stimulation of various components of the hippocampal formation were identified with the use of [¹⁴C]2-deoxyglucose (2-DG) autoradiography. The results of these experiments, conducted in the rat, showed that in the absence of elicited afterdischarge activity, stimulation of either the CA1 or CA3 field of the dorsal hippocampus resulted in bilateral metabolic activation of only the dorsal hippocampus as well as of a relatively restricted region within the dorsomedial aspect of the lateral septal nucleus, bilaterally. In contrast, stimulation of either the CA1 or CA3 field of the ventral hippocampus resulted in bilateral activation of the ventral hippocampus and no region of the dorsal hippocampus. Following such stimulation, the lateral septal nucleus was also labeled bilaterally, but the activated regions were situated in a position ventrolateral to those resulting from stimulation at dorsal levels. Stimulation of the subicular cortex, in contrast, resulted in only ipsilateral activation of the hippocampal formation and lateral septal nucleus. Further rostral levels of the lateral septal nucleus were noted to be activated following stimulation of subicular cortex as compared to stimulation of the cornu Ammonis.The hypothalamus was directly activated by two pathways, the postcommissural fornix and the medial corticohypothalamic tract. Following stimulation at dorsal and posterior levels of CA1 and the subiculum, the mammillary bodies were demonstrably labeled by input from the postcommissural fornix. Regions of the medial hypothalamus were activated via the medial corticohypothalamic tract following stimulation of the ventral subiculum.The amygdala, stria terminalis and its bed nucleus were also shown to be demonstrably activated following stimulation of the ventral subiculum, ventral CAl field and posterior prosubiculum. This pathway may represent an additional route by which hippocampal modulation may indirectly modulate hypothalamic function.The presence of elicited afterdischarges resulted in more extensive patterns of metabolic labeling within the hippocampal formation and lateral septal nuclei as compared to experiments in which afterdischarges were not elicited. The extent of the demonstrable labeling, both within, and extrinsic to the hippocampal formation appeared to be a function of the duration and severity of the elicited seizure discharge. Additional structures which were demonstrably labeled following the elicitation of seizure activity include the entorhinal cortex-prepyriform area, amygdala, substantia innominata, putamen, substantia nigra, olfactory and prefrontal cortices and medial thalamic nuclei.     

Hypothalamic norepinephrine mediates limbic effects on adrenocortical secretion

The purpose of this study was to elucidate the role of norepinephrine (NE) in the mediation of adrenocortical responses following limbic stimuli. The effects of stimulation of the dorsal and ventral hippocampus and the midbrain reticular formation on the plasma corticosterone (CS) levels was studied in rats with vehicle or 6-hydroxydopamine (6-OHDA) injected bilaterally into the paraventricular nucleus of the hypothalamus (PVN). The injection of 6-OHDA caused a very significant reduction in the concentration of PVN NE and blocked the rise in plasma CS following the stimulation of the above three limbic structures. The basal CS level and the response to ether stress were not affected. The present study supports previous observations on the stimulatory role of NE on CS secretion and that the modulatory effects of extrahypothalamic limbic structures on the adrenocortical activity depend on the presence of NE in the PVN.     

Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion

The purpose of this study was to further elucidate the role of serotonin (5-HT) in adrenocortical regulation. The effects of stimulating the frontal cortex and extrahypothalamic limbic structures, on plasma corticosterone (CS) responses, were studied in rats with vehicle or 5,7-dihydroxytryptamine (5,7-DHT) injection into the midbrain raphe nuclei. In another group of rats the neurotoxin was injected locally into the paraventricular nucleus (PVN) in view of its importance in adrenocortical regulation, and the effects of photic and dorsal hippocampal stimulation on plasma CS were studied. 5,7-DHT caused a significant depletion of hypothalamic 5-HT and blocked the rise in plasma CS following the stimulation of the above neural modalities. These studies suggest that the PVN 5-HT mediates the adrenocortical responses following afferent neural stimuli.     

Locomotion elicited by lateral hypothalamic stimulation in the anesthetized rat does not require the dorsal midbrain

Locomotor stepping elicited by lateral hypothalamic stimulation in the anesthetized rat is blocked by lesions in the anterior ventromedial midbrain. This study determined in acute experiments whether the dorsal midbrain regions implicated in locomotion were also part of the necessary pathway. Rats were anesthetized with Nembutal and held in a stereotaxic apparatus so that stepping responses rotated a wheel. Stepping was elicited by stimulation of the lateral hypothalamus (up to 100 microA, 0.5 ms cathodal pulses, 50 Hz, 10-s train length). Nine rats received unilateral lesions ipsilateral to the locomotor electrode and 3 rats received bilateral lesions. None of the dorsal midbrain lesions reduced locomotion elicited by ipsilateral lateral hypothalamic stimulation. Therefore the following regions are unnecessary for this type of locomotion: the dorsal and lateral central gray, the tegmentum lateral to the central gray, and in particular the area cuneiformis and the dorsal aspect of the pedunculopontine region. The neural systems required for lateral hypothalamic locomotion are located ventral to the superior cerebellar peduncle.     

The topographic organization of hypothalamic and brain stem projections to the hippocampus

Direct projections primarily ipsilateral to hippocampus from medial septal, diagonal band, supramammillary, submammillothalamic, locus coeruleus, and dorsal and medianus raphe nuclei were demonstrated. The locus coeruleus projects primarily through the cingulum and fornix superior to the dorsal posterior hippocampus, with its terminal fields in the stratum lacunosum moleculare of the subiculum and areas CA 1-CA 2 of the dorsal posterior hippocampus. LC projections to the granular layer of the dentate hilus were not found. Raphe nuclei project through the cingulum, fornix superior, and primarily the fimbria, to the dorsal and ventral posterior hippocampus, with their terminal fields in the stratum lacunosum moleculare of the dorsal posterior subicular region, stratum radiatum of CA 1-CA 3 in the dorsal hippocampus, and the stratum polymorph of the dentate gyrus, primarily in its superficial part. Raphe projections to the anterior hippocampal rudiment were found. However, no projection was found to the subiculum of the ventral posterior hippocampus, nor to stratum oriens. Hypothalamic nuclei project through the fornix superior and the fimbria, mainly to the dorsal posterior hippocampus with abundant terminal fibers in the depth of the dentate hilus. Smaller cells in these hypothalamic nuclei appear projecting to the ventral hippocampus. The number of neurons in the entorhinal area, the diagonal band, and the hypothalamic nuclei projecting to the hippocampus suggests these groups as the main sources of the extrinsic hippocampal afferents. In addition, they may also serve as relay stations for inputs from more caudal nuclei, and the topographic organization of their terminal fields as described herein may have important functional implications.     

The topographical organization of the hippocampal projection to the septal area: a comparative neuroanatomical analysis in the gerbil, rat, rabbit, and cat

An experiment was performed to determine the origin of the projection from the hippocampus to the septal area in the subrimate mammalian nervous system. Lesions were made by aspiration or by radio frequency in 4 gerbils, 17 rats, 8 rabbits, and 7 cats. Survival times varied from 2–5 days. Tissues were stained principally with the Fink Heimer I method for identification of degenerating axons and their terminals. Following lesions destroying any one or more of the fields of the dorsal hippocampus of the gerbil, rat, rabbit, or cat, terminal degeneration was observed only in the medial septal area, olfactory tubercle, and adjacent portions of the diagonal band. In addition, lesions producing total destruction of all dorsal hippocampal fields also resulted in the presence of terminal degeneration restricted to the medial septal area. In contrast, superficial lesions of field CA1 of the ventral hippocampus produced terminal degeneration in the lateral septal area, nucleus accumbens, olfactory tubercle, and adjacent portions of the diagonal band. Similar findings were also observed following more widespread lesions of the ventral hippocampus which produced damage to other CA fields as well. Superficial lesions of the posterior crus of the hippocampus (i.e., a position midway between dorsal and ventral hippocampus) resulted in terminal degeneration localized to an intermediolateral region of the septum. Combined lesions of the dorsal hippocampus and fimbria produced widespread terminal degeneration in both the lateral and medial septum indicating that the axons contained within the fimbria arise only from the ventral hippocampus. Finally, lesions of the medial and lateral segments of the fornix of the cat produced terminal degeneration in the medial and lateral regions of the septum, respectively. These findings, collectively, indicate that the origin of the topographical projection to the medial and lateral septum are the dorsal and ventral hippocampus, respectively. This projection is unrelated to cytoarchitectonic fields within the hippocampus and is also invariant among the species considered in this study.     

Electrical stimulation of the dorsal hippocampus caused a long lasting inhibition of ACTH and adrenocortical responses to photic stimuli in freely moving rats

The effect of a single train of electrical hippocampal stimulation on ACTH and corticosterone (CS) responses to subsequent photic stimulation was studied in freely moving male rats. The hippocampal stimulation inhibited the stress-induced rise [corrected] in serum CS levels up to 150 h when compared to sham stimulated animals. This effect did not exist at 300 h following stimulation. This sustained hippocampal inhibitory effect on the adrenocortical response, which was not reported previously, was partially abolished by section of the dorsal fornix. The present data demonstrate that dorsal hippocampal stimulation has a long lasting inhibitory effect on pituitary adrenocortical secretion following neural stimuli and this is partially mediated by the dorsal fornix.     

The connections of the septal region in the rat

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.     

An analysis of the mechanisms underlying hippocampal control of hypothalamically-elicited aggression in the cat

An experiment was performed to determine the role of the hippocampal formation in the regulation of quiet biting attack behavior elicited from electrical stimulation of the hypothalamus. The results showed clearly that stimulation of the dorsal hippocampus resulted in an increased latency to quiet biting attack and that ventral hippocampal stimulation resulted in a decreased latency to quiet biting attack.In addition, the results indicate that those sites in the ventral hippocampal formation from which facilitation of attack can be produced are linked to sensory mechanisms associated with trigeminal reflexes established during hypothalamic stimulation inasmuch as stimulation of these sites increase the lateral extent of the effective sensory field of the lipline. No effect was observed upon a motor component of the jaw-opening response — the latency to jaw-opening — during ventral hippocampal stimulation. In contrast, no effects were observed upon either sensory or motor components of the hypothalamically-elicited jaw-opening response as a result of stimulation of dorsal hippocampal sites.Deoxyglucose autoradiography revealed that the major effect of stimulation of modulatory sites in both the dorsal and ventral hippocampal formation was exerted upon the lateral septal nucleus. Thus, it is proposed that hippocampal modulation of hypothalamically-elicited quiet biting attack is mediated primarily through the lateral septal nucleus.     

Efferent connections of the hippocampal formation in the rat.

In this investigation the projections of the hippocampal formation to the septal area and hypothalamus were studied in the rat with the combined use of 3H-amino acid radioautography and horseradish peroxidase histochemistry. The results indicate that all of the fibers which project to the hypothalamus and the majority of fibers which project to the septum arise from the subicular cortex and not from hippocampal pyramidal cells. The projection to both of these areas are topographically organized along the longitudinal axis of the hippocampal formation. Specifically, fibers from subicular cortical cells situated at the septal end of the hippocampal formation which project through the medial part of the dorsal fornix terminate in the dorsomedial quadrant of the lateral septal nucleus and in the dorsal portion of the pars posterior of the medial mammillary nucleus. Fibers from progressively more posteroventral levels of the hippocampal formation which project through more lateral portions of the dorsal fornix and fimbria terminate in progressively lateral and ventral quadrants of the lateral septal nucleus and in progressively more ventral portions of the pars posterior. Concerning the specific origin of the fornix system, fibers from only the prosubiculum and subiculum project through both the pre- and postcommissural fornix. Hippocampal pyramidal cells from all CA fields have a restricted projection through the precommissural fornix and terminate in the caudal half of the septum while the presubiculum projects solely through the postcommissural fornix. The medial corticohypothalamic tract (MCHT) was found to arise from cells located in anterior ventral levels of the subicular cortex. Fibers from this tract appeared to be distributed throughout the pericellular region of the entire ventromedial extent of the hypothalamus from the level of the suprachiasmatic nucleus through the level of the medial mammillary nucleus. In this way, the mammillary bodies receive input from the subicular cortex via two routes: the descending column of the fornix and the MCHT.     

Hippocampal influence on hyperreactivity induced by septal lesions.

Rats were tested for their responses to 4 stimuli in order to measure hyperreactivity. Animals with septal lesions emitted the expected hyperreactivity. Lesions of the postcommisural fornix, precommissural fornix, or anterior hippocampus, administered 16 days prior to a septal lesion, blocked the expected hyperreactivity. Lesions localized to the medial or the lateral fibers of the fornix decreased the magnitude the duration of the expected hyperreactivity following septal lesions but did not block it. Lesions of the posterior hippocampus-entorhinal cortex had no reliable effect on the expected hyperreactivity after septal lesions. These data indicate that the appearance of hyperreactivity following a septal lesion depends upon a circuit involving the septum, precommissural fornix, anterior hippocampus, postcommissural fornix, and hypothalamus, and document an important functional relationship between the septum, anterior hippocampus, and hypothalamus.     

Efferents from the medial anterior hypothalamic area in the guinea pig

Medial anterior hypothalamic connections were studied with H³-proline and autoradiography. Most of the axons projected to other hypothalamic nuclei. The major pathways were found ventral medial to the fornix and in the periventricular tract. Substantial projections were apparent in the ventromedial and dorsomedial nuclei with less label in the arcuate nucleus. The dorsal premammillary nuclei were labeled bilaterally, particularly with more caudal injections of anterior hypothalamus. Efferents were evident in the posterior hypothalamus and continued into the central gray of the midbrain. Labeled fibers reached the ventral tegmental area and in the reticular formation were traced only through pons. Rostral projections were to the medial and lateral preoptic areas and ventral lateral septum. The bed nucleus of stria terminalis was labeled and a very few fibers reached the medial amygdaloid nucleus. The periventricular nucleus of thalamus was labeled.     

Reset of hippocampal rhythmical activities by afferent stimulation

Physostigmine induced theta rhythm and unit activity were recorded from the dorsal hippocampus in immobilized locally anesthetized rats. Correlations between theta and rhythmical unit activity and their modifications by hippocampal afferent stimulation were studied. The principal finding was that electrical stimulation of afferents reset theta and rhythmical unit activity in phase. Poststimulus theta displayed a variable frequency which depended upon the structure stimulated. Lower frequencies were evoked by septal, higher frequencies by entorhinal and reticular formation stimulations. When theta rhythms were absent either by spontaneous disappearance or as a consequence of lesions in the fornix superior of septum, the reset was not observed. The reset of the theta rhythms and unit activity by afferent stimulation, suggests that the hippocampus may participate in timing mechanisms.     

Adrenal responses and neurotransmitters in posterior hypothalamic deafferentation

The effects of a small posterior hypothalamic deafferentation (PHD) on adrenocortical responses to peripheral neural stimuli were investigated in rats. PHD inhibited the rise in plasma corticosterone (CS) following photic and acoustic stimulation, but did not affect the adrenocortical response following sciatic nerve stimulation. PHD did not change the content of norepinephrine in the paraventricular nucleus of the hypothalamus, however, it reduced the serotonin content by about 30%. The possible role of serotonin or of another tonic caudal input into the hypothalamus for the activation of the pituitary-adrenocortical axis, following certain neural stimuli, is discussed.     

Afferent projections related to attack sites in the ventral midbrain tegmentum of the cat

Quiet attack was elicited by electrical stimulation of the ventrolateral midbrain tegmentum of the cat. The paw was not used other than to position or hold the rat during the bite. Bites were directed toward the head and neck region and were not accompanied by autonomic responses other than pupillary dilation and sometimes slight piloerection on the back.Horseradish peroxidase was deposited at the attack sites. Cells labeled with the peroxidase reaction product were located in gyrus proreus, gyrus genualis, nucleus accumbens, bed nucleus of the stria terminalis, bed nucleus of the anterior commissure, nucleus of the diagonal band, substantia innominata, anterior amygdaloid area, ventromedial hypothalamic area, paraventricular nucleus, perifornical hypothalamic area, lateral hypothalamic area, dorsal hypothalamic area, fields of Forel, midbrain reticular formation, superior colliculus, ventral central grey, lateral central gray, locus coeruleus, parabrachial nuclei, nucleus of the lateral lemniscus, oral pontine reticular nucleus, and the dorsal raphe. Other regions were less prominently labeled. Previous studies have shown most of these sites to have some involvement in attack.     

Efferent connectivity of the hippocampal formation of the zebra finch (Taenopygia guttata): An anterograde pathway tracing study using Phaseolus vulgaris leucoagglutinin

The avian hippocampal formation (HP) is considered to be homologous to the mammalian hippocampus, being involved in memory formation and spatial memory in particular. The subdivisions and boundaries of the pigeon hippocampus have been defined previously by various morphological methods to detect further similarities with the mammalian homologue. We studied the efferent projections of the zebra finch hippocampus by applying Phaseolus vulgaris leucoagglutinin, and three main subdivisions were distinguished on the basis of the connectivity patterns. Dorsolateral injections gave rise to projections innervating the rostralmost extension of the HP, a laminar complex including the dorsal and ventral hyperstriata and the lamina frontalis superior, the rostral lobus parolfactorius, the medial and ventral paleostriatal regions, the lateral septal nucleus, the nucleus of the diagonal band, the dorsolateral corticoid area, the archistriatum posterius, and the nucleus taeniae in the telencephalon. In the diencephalon, labelled axons were seen in the periventricular and lateral hypothalamus, including the lateral mammillary nuclei, and in the dorsolateral and the dorsomedial posterior thalamic nuclei, whereas, in the midbrain, only the area ventralis of Tsai contained hippocampal fibres. With the exception of the bilateral archistriatal efferents, all projections were ipsilateral. Dorsomedial injections gave rise to a local fibre system that was almost completely restricted to the ipsilateral hippocampal formation. In addition, lectin-containing fibres continued in the dorsal septal region and a thin band in the hyperstriatum accessorium, adjacent to the lateral ventricle. Ventral injections gave rise to axons innervating the dorsolateral subdivision ipsilaterally and bilaterally the medial septal nuclei and the contralateral ventral hippocampus. © 1996 Wiley-Liss, Inc.     

Afferent connections of septal nuclei of the domestic chick (Gallus domesticus): a retrograde pathway tracing study

The afferents to the septum of the domestic chicken were studied using retrograde tracers, rhodamine conjugated latex bead or Fast Blue, placed in different septal subregions. The results were verified by anterograde tracer injections deposited to selected areas. The main telencephalic afferents to the septum arise ipsilaterally from the hippocampal formation, dorsolateral corticoid area, piriform cortex, amygdaloid pallium, and the ventral pallidum. Contralateral afferents originate from the lateral septum and the amygdaloid pallium. A massive bilateral projection arises from the lateral hypothalamus. Other hypothalamic afferents arise from the periventricular, paraventricular and anterior medial nuclei, and the premammillary and mammillary areas. The dorsal thalamic nuclei (dorsal medial anterior and posterior) and the reticular dorsal nuclei also contribute septal afferents. Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, locus coeruleus, ventral subcoeruleus nucleus, and raphe nuclei. The main terminal fields for septal afferents lie in the lateral septal nucleus and the belt of medial septal nucleus. The core of the latter is invaded mainly by fibers from the brainstem, presumably belonging to the ascending activating system. The septal afferents of the chicken are largely similar to those of other avian and nonavian species. The most prominent differences with previous pigeon data were found in the subregional selectivity of the hippocampal formation, dorsolateral corticoid area, mammillary nuclei, some dorsal thalamic nuclei, substantia nigra, and subcoeruleus nuclei in their projections to defined septal nuclei.     

Hippocampal electrical correlates of free behavior and behavior induced by stimualtion of two hypothalamic- hippocampal systems in the cat.

Bilateral dorsal and ventral hippocampal and anterior and posterior neocortical electrical activity was recorded in 11 cats during free behavior situations and during stimulation of medial and lateral hypothalamic systems which influence hippocampal electrical activity and behavior in distinct and contrasting ways. Behavioral states characterized by alertness, attentiveness, scanning, or investigatory activity were accompanied by hippocampal theta rhythm and by desynchronization of neocortical electrical activity. Behavioral states characterized by relaxed wakefulness, inattentiveness, or drowsiness were accompanied by high voltage irregular patterns of electrical activity in the hippocampus with no organized theta rhythms. Specific behaviors (alerting, orienting, scanning, or investigatory) emerging from relaxed behavioral states occurred concomitantly with hippocampal theta rhythm. Electrical stimulation of the medial hypothalamic system at 100 Hz elicited hippocampal theta rhythm and specific behaviors of alerting, orienting, scanning, and investigatory activity. In contrast, lateral hypothalamic stimulation at 100 Hz caused low voltage desynchronization of hippocampal electrical activity accompanied by postural stability and fixation of gaze. The relation of hippocampal theta rhythm to behavior is discussed in terms of brain stem-hypothalamic-hippocampal systems.     

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.