Microsurgical anatomy of the amygdaloid body and its connections.

The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several neuropsychiatric disorders renewed the interest in the study of its functional Neuroanatomy. In this scenario, we felt that a morphological study focused on the amygdaloid body and its connections could improve the understanding of the possible  implications in functional neurosurgery. With this purpose we performed a morfological study using nine formalin-fixed human hemispheres dissected under microscopic magnification by using the fiber dissection technique originally described by Klingler. In our results the  amygdaloid body presents two divergent projection systems named dorsal and ventral amygdalofugal pathways connecting the nuclear complex with the septum and the hypothalamus. Furthermore, the amygdaloid body is connected with the hippocampus through the amygdalo-hippocampal bundle, with the anterolateral temporal cortex through the amygdalo-temporalis fascicle, the anterior commissure and the temporo-pulvinar bundle of Arnold, with the insular cortex through the lateral olfactory stria, with the ambiens gyrus, the para-hippocampal gyrus and the basal forebrain through the cingulum, and with the frontal cortex through the uncinate fascicle. Finally, the amygdaloid body is connected with the brainstem through the medial forebrain bundle. Our description of the topographic anatomy of the amygdaloid body and its connections, hopefully represents a useful tool for clinicians and scientists, both in the scope of application and speculation.

Tractography Study of Deep Brain Stimulation of the Anterior Cingulate Cortex in Chronic Pain: Key to Improve the Targeting.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.

An anatomic review of thalamolimbic fiber tractography: ultra-high resolution direct visualization of thalamolimbic fibers anterior thalamic radiation, superolateral and inferomedial medial forebrain bundles, and newly identified septum pellucidum tract.

BACKGROUND: Images obtained through ultra-high-field 7.0-tesla magnetic resonance imaging with track-density imaging provide clear, high-resolution tractograms that have been hitherto unavailable, especially in deep brain areas such as the limbic and thalamic regions. This study is a largely pictorial description of the deep fiber tracts in the brain using track-density images obtained with 7.0-T diffusion-weighted imaging. METHODS: To identify the fiber tracts, we selected 3 sets of tractograms and performed interaxis correlation between them. These tractograms offered an opportunity to extract new information in areas that have previously been difficult to examine using either in vivo or in vitro human brain tractography. RESULTS: With this new technique, we identified 4 fiber tracts that have not previously been directly visualized in vivo: septum pellucidum tract, anterior thalamic radiation, superolateral medial forebrain bundle, and inferomedial forebrain bundle. CONCLUSIONS: We present the high-resolution images as a tool for researchers and clinicians working with neurodegenerative and psychiatric diseases, such as Parkinson disease, Alzheimer disease, and depression, in which the accurate positioning of deep brain stimulation is essential for precise targeting of nuclei and fiber tracts.

Human medial forebrain bundle (MFB) and anterior thalamic radiation (ATR): imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression.

The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

Priming of locomotor initiation by electrical stimulation in the hypothalamus and preoptic region in the anesthetized rat.

Electrical stimulation at a locomotor site can prime (i.e., shorten the latency to initiate) stepping elicited by subsequent stimulation of the same or a different site. We tested for the priming effect in representative sites along the medial forebrain bundle, and determined if its magnitude showed regional differences. Rats (n = 20) were anesthetized with Nembutal and held in a stereotaxic apparatus over a wheel. Stepping was detected by accelerometers attached to the hindlimbs. Priming and test trains of stimulation (0.5-ms cathodal pulses, 50 Hz, 25-75 microA, 7-9-s train duration) separated by 20 s were delivered every 90 s. When the priming and test stimulations were applied to the same site, the priming effects were similar along the entire extent of the medial forebrain bundle. When the priming and test sites were different, the priming effect depended on their relative positions. Anterior stimulation primed posterior sites at magnitude comparable to those produced by stimulating the same posterior site. Posterior stimulation primed anterior sites at a level half of that produced by stimulation of the same anterior site. This pattern was found for priming and test sites that were ipsilateral and contralateral. Priming is a general and robust phenomenon with properties that may be useful for studying locomotor initiation pathways.

Subtelencephalic visual discrimination in selected lines of Japanese quail.

We studied visual discrimination capabilities of the avian brain stem in genetic lines of Japanese quail artificially selected for unconditional approach preference for blue, red or an achromatic pattern stimulus. Complete telencephalectomy did not abolish approach behavior and visual discrimination. Our data indicate that visual feature extraction and motor coordination related to early approach preferences in birds may be mediated by brain stem and thalamic circuitries which do not require input from higher level visual and motor regions.

Interactions between amygdaloid and hypothalamic self-stimulation: a re-examination.

The function relating bar-pressing rate to the frequency of cathodal pulses was obtained in rats self-stimulating with amygdaloid (AMY) and lateral hypothalamic (LH) electrodes. The maximum self-stimulation (SS) rates in the AMY was found to be very low, compared to the LH. Concurrent stimulation with pairs of AMY-LH pulses did not shift the rate-frequency functional laterally, indicating the absence of summation of the two rewarding effects. In a second experiment, concurrent AMY-LH stimulation (using sub-threshold intensity LH pulses) facilitated bar-pressing for AMY stimulation (it increased the slope of the AMY rate-frequency function) without shifting this function laterally. In a third experiment, subjects were given a choice between a pulse frequency yielding maximal AMY rate and a series of higher pulse frequencies. Subjects consistently preferred the higher frequency values, attesting that the maximum AMY rates were not constrained by a saturating reinforcing effect. In a fourth experiment, subjects were given a choice between AMY stimulation and concurrent AMY-LH stimulation, using low intensity LH pulses. Subjects showed no preference for either stimulation condition, although rates were higher for the latter condition. These findings suggest that the maximum rate for AMY stimulation was constrained by factors interfering with bar-pressing and that the effect of these factors was attenuated by co-activation of the LH. In a fifth experiment, pre-treatment with phenobarbital mimicked the rate-enhancing effect of concurrent AMY-LH stimulation for 2 of the 4 subjects tested. This finding suggests that the LH pulses contributed to attenuate seizure activity accompanying AMY SS. In a final experiment, AMY SS rates were also increased by co-activation of rewarding sites in the rostral MFB but not the dorsal raphe, suggesting an anatomical specificity of this effect.

Projections of the medial preoptic nucleus: a Phaseolus vulgaris leucoagglutinin anterograde tract-tracing study in the rat.

The projections of the medial preoptic nucleus (MPN) were examined by making injections of the anterogradely transported lectin Phaseolus vulgaris leucoagglutinin (PHA-L) into the MPN and charting the distribution of labeled fibers. The evidence indicates that the MPN projects extensively to widely distributed regions in both the forebrain and brainstem, most of which also supply inputs to the nucleus. An important neuroendocrine role for the MPN is underscored by its extensive projections to almost all parts of the periventricular zone of the hypothalamus, including the anteroventral periventricular, anterior part of the periventricular, paraventricular (PVH), and arcuate nuclei, and a role in autonomic mechanisms is indicated by projections to such regions as the dorsal and lateral parvicellular parts of the PVH, the lateral parabrachial nucleus, and the nucleus of the solitary tract. Other projections of the MPN suggest participation in the initiation of specific motivated behaviors. For example, inputs to two nuclei of the medial zone of the hypothalamus, the ventromedial and dorsomedial nuclei, may be related to the control of reproductive and ingestive behaviors, respectively, although the possible functional significance of a strong projection to the ventral premammillary nucleus is presently unclear. The execution of these behaviors may involve activation of somatomotor regions via projections to the substantia innominata, zona incerta, ventral tegmental area, and pedunculopontine nucleus. Similarly, inputs to other regions that project directly to the spinal cord, such as the periaqueductal gray, the laterodorsal tegmental nucleus, certain medullary raphe nuclei, and the magnocellular reticular nucleus may also be involved in modulating somatic and/or autonomic reflexes. Finally, the MPN may influence a wide variety of physiological mechanisms and behaviors through its massive projections to areas like the ventral part of the lateral septal nucleus, the bed nucleus of the stria terminalis, the lateral hypothalamic area, the supramammillary nucleus, and the ventral tegmental area, all of which have extensive connections with regions along the medial forebrain bundle. Although the PHA-L method does not allow a clear demonstration of possible differential projections from each subdivision of the MPN, our results suggest that each of them does give rise to a unique pattern of outputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Some anatomical observations on the projections from the hypothalamus to brainstem and spinal cord: an HRP and autoradiographic tracing study in the cat.

The hypothalamus is closely involved in a wide variety of behavioral, autonomic, visceral, and endocrine functions. To find out which descending pathways are involved in these functions, we investigated them by horseradish peroxidase (HRP) and autoradiographic tracing techniques. HRP injections at various levels of the spinal cord resulted in a nearly uniform distribution of HRP-labeled neurons in most areas of the hypothalamus except for the anterior part. After HRP injections in the raphe magnus (NRM) and adjoining tegmentum the distribution of labeled neurons was again uniform, but many were found in the anterior hypothalamus as well. Injections of 3H-leucine in the hypothalamus demonstrated that: The anterior hypothalamic area sent many fibers through the medial forebrain bundle (MFB) to terminate in the ventral tegmental area of Tsai (VTA), the rostral raphe nuclei, the nucleus Edinger-Westphal, the dorsal part of the substantia nigra, the periaqueductal gray (PAG), and the interpeduncular nuclei. Further caudally a lateral fiber stream (mainly derived from the lateral parts of the anterior hypothalamic area) distributed fibers to the parabrachial nuclei, nucleus subcoeruleus, locus coeruleus, the micturition-coordinating region, the caudal brainstem lateral tegmentum, and the solitary and dorsal vagal nucleus. Furthermore, a medial fiber stream (mainly derived from the medial parts of the anterior hypothalamic area) distributed fibers to the superior central and dorsal raphe nucleus and to the NRM, nucleus raphe pallidus (NRP), and adjoining tegmentum. The medial and posterior hypothalamic area including the paraventricular hypothalamic nucleus (PVN) sent fibers to approximately the same mesencephalic structures as the anterior hypothalamic area. Further caudally two different fiber bundles were observed. A medial stream distributed labeled fibers to the NRM, rostral NRP, the upper thoracic intermediolateral cell group, and spinal lamina X. A second and well-defined fiber stream, probably derived from the PVN, distributed many fibers to specific parts of the lateral tegmental field, to the solitary and dorsal vagal nuclei, and, in the spinal cord, to lamina I and X, to the thoracolumbar and sacral intermediolateral cell column, and to the nucleus of Onuf. The lateral hypothalamic area sent many labeled fibers to the lateral part of the brainstem and many terminated in the caudal brainstem lateral tegmentum, including the parabrachial nuclei, locus coeruleus, nucleus subcoeruleus, and the solitary and dorsal vagal nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence implicating descending fibers in self-stimulation of the medial forebrain bundle.

The role of ascending and descending fibers in self-stimulation of the lateral hypothalamus and ventral tegmental area in the rat was assessed by noting whether anodal hyperpolarization of one of these sites could reduce the rewarding effect of stimulating the other site. Strength-duration curves were obtained by psychophysical means, with one of the depth electrodes serving as the cathode and the other as the anode. It was anticipated that at long pulse durations, conduction in some of the fibers stimulated at the cathode would be blocked at the anode. At shorter durations, the anodal hyperpolarization should have dissipated before the arrival of the action potentials triggered by the cathode. Thus, the predicted effect of the block was to bend the strength-duration curves obtained with two depth electrodes upward at long pulse durations, provided that the anode lay between the cathode and the efferent stages of the pathway responsible for the rewarding effect. To control for possible differences in the density of the reward substrate in the lateral hypothalamic and ventral tegmental areas, the strength-duration curves obtained with a given cathode and a depth anode were compared to curves obtained with the same cathode but with an anode consisting of a set of skull screws. It was expected that the concentrated current entering from the depth anode would much more effectively block conduction in the medial forebrain bundle than the diffuse current entering from the large, distant skull screws. The predicted change in the shape of the strength-duration curves was observed only when the ventral tegmental electrode served as the anode and the lateral hypothalamic electrode as the cathode. This is consistent with the notion that in at least some of the neurons responsible for the rewarding effect, action potentials elicited by the lateral hypothalamic electrode had to pass through the ventral tegmental area in order to reach the efferent stages of the reward pathway. In the simplest anatomical arrangement consonant with this view, the somata of these cells lie in the forebrain and give rise to descending axons. As a test of the hypothesis that anodal block was responsible for changing the shape of the strength-duration curve obtained with the ventral tegmental anode, a psychophysical version of the collision test was used to determine whether the tips of the lateral hypothalamic and ventral tegmental electrodes were indeed linked by a common set of reward-related fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

[Intrahypothalamic connections of the lateral hypothalamus]. / Vnutrigipotalamicheskie sviazi lateral'nogo gipotalamusa.

Using the axon degeneration method by R. Fink and L. Heimer, organization of intrathalamic connections between various areas of the lateral hypothalamus have been studied after unisided electrolitic lesion. At any location of the injury foci, similar patterns are observed in ipsilateral distribution of degenerating fibers along the whole lateral preoptico-hypothalamic area. The most massive degeneration is observed in the zone where the medial forebrain bundle (MFB) fibers run. The degenerating fibers spread forward--into the septal area, and backward--into the mesencephalic part of the brain. The rostral and caudal parts of the lateral hypothalamus, taking part in formation of the MFB collateralies towards the thalamus, are connected with various thalamic nuclei. Massive preterminal degeneration in the perifornical zone and single argerophile granules in the medial hypothalamus convincingly demonstrate an important role of the intermediate zone for connections of its medial and lateral parts with each other. The conclusion that the intrahypothalamic connections of the lateral hypothalamus are realized within the MFB system supports the modern notion on a close connection of the lateral hypothalamus with the system of longitudinal diffuse bundles of fibers of the medial anterocerebral pathway that run through it.

Efferent projections from the lateral hypothalamus in the guinea pig: an autoradiographic study.

Autoradiography was employed to investigate the efferent projections from the lateral hypothalamus in the guinea pig. Lateral hypothalamic axons were traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced along the medial forebrain bundle in both ascending and descending directions. Anteriorly, the label was traced to the lateral preoptic area, diagonal band of Broca, and septal nuclei. Posterior projections included the ventral tegmental area of Tsai, central gray matter and the reticular formation throughout the brain stem. Laterally, the lateral hypothalamic efferents were found in the stria terminalis, amygdala and globus pallidus. Dorsally, the lateral hypothalamic axons projected to the midline nuclei of the thalamus and bilaterally to the lateral habenular nuclei. Projections to the medial hypothalamus included a labeled fiber bundle to the internal layer of the median eminence and to the posterior lobe of the pituitary gland. Labeled fibers and diffuse label were also found in some areas contralateral to the injection site.

Hypothalamic self-stimulation in rats with one hemisphere isolated anterior to the midbrain and the other hemisphere devoid of the telencephalon.

The telencephalon was removed unilaterally in rats. In addition, the forebrain of the other hemisphere was isolated from its brain stem by a precollicular transverse cut. This preparation was then tested for self-stimulation via electrodes implanted in the region of the lateral hypothalamus and medial forebrain bundle (LH-MFB) of either hemisphere. Self-stimulation was found to be intact in both hemispheres. Possible pathways connecting the LH-MFB region of one hemisphere to the contralateral diencephalon were also investigated in the bilaterally detelencephalized rat. The technique of retrograde transport of horseradish peroxidase was used for this purpose. Some fibers from the LH-MFB of one hemisphere were found to decussate to the other hemisphere by way of the thalamic commissure. The supraoptic decussation as well as diffusely organized interdiencephalic connections provide additional routes for interhemispheric LH-MFB projections.

Origins of substance P-containing fibers in the lateral septal area of young rats: immunohistochemical analysis of experimental manipulations.

The majority of substance P-like immunoreactive (SPLI) fibers in the lateral septal area (LS) are supplied by SPLI cells in the area (BAL) between the anterior hypothalamic nucleus and the lateral hypothalamus, and by those in the nucleus latero-dorsalis tegmenti (TLD). These conclusions are based on following: (1) Unilateral destruction of the BAL resulted in an ipsilateral decrease in the septal SPLI fibers similar to that seen after the destruction of the TLD, and (2) simultaneous destruction of the BAL and TLD caused a marked reduction of SPLI fibers in the LS on the operated side. The possibility that the destruction of the BAL affected the ascending SPLI system from the TLD seems to be excluded, because (1) the destruction of the TLD resulted in a decrease in SPLI fibers in the ipsilateral medial forebrain bundle (MFB), but failed to reduce the number of SPLI fibers in the BAL, and (2) the destruction of the BAL caused a decrease in SPLI fibers in the perifornical area rostral to the lesion, but failed to reduce the number of SPLI fibers in the MFB. These facts further suggest that ascending SPLI fibers from the BAL travel in the perifornical area and those from the TLD pass through the MFB. It should be noted that a few SPLI fibers remained intact following the simultaneous destruction of the BAL and TLD. The present study suggests that these remaining SPLI fibers might be innervated by intrinsic SPLI cells. In support of this, several SPLI cells were detected in the septal area after colchicine pretreatment.

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). I. Cytoarchitectonic organization.

The cytoarchitectonic organization of the posterior hypothalamus of the cynomolgus monkey (Macaca fascicularis) was analyzed in Nissl, Golgi, acetylcholinesterase, and reduced silver preparations. The region consists of a number of cell masses that differ considerably in their discreteness and in the homogeneity of their neuronal populations. The nuclei identified include: the medial mamillary nucleus (in which at least three distinct subdivisions can be recognized--a pars medialis, a pars lateralis, and a pars basalis); the small-celled nucleus intercalatus; the large-celled lateral mamillary nucleus; a single premamillary nucleus; the tuberomamillary nucleus; the posterior hypothalamic nucleus; the caudal extension of the lateral hypothalamic area; the supramamillary area; and the paramamillary nucleus (which appears to correspond to the nucleus of the ansa lenticularis of other workers). As a basis for the subsequent experimental study of the efferent connections of the posterior hypothalamus, the location of each of these cell masses is described and illustrated in a series of low-power photomicrographs, as are the form and distribution of the resident neuronal populations of the various components of the mamillary complex as seen in Golgi preparations.

The morphology and connections of the posterior hypothalamus in the cynomolgus monkey (Macaca fascicularis). II. Efferent connections.

The efferent connections of the posterior hypothalamus have been analyzed autoradiographically in a series of eight cynomolgus monkey (Macaca fascicularis) brains with injections of 3H-amino acids in different regions of the mamillary complex and the surrounding areas. The medial mamillary nucleus was found to project through the mamillothalamic tract to the ipsilateral anteroventral, anteromedial, and interanteromedial nuclei, and by way of the mamillotegmental tract principally to the deep tegmental nucleus (of Gudden). It also appears to contribute fibers to the medial forebrain bundle, some of which reach as far rostrally as the medial septal nucleus. The lateral mamillary nucleus projects through the mamillothalamic tract bilaterally upon the anterodorsal nuclei of the thalamus, and through the mamillotegmental system to the dorsal tegmental nucleus; it also appears to contribute fibers to the medial forebrain bundle. The supramamillary area has extensive ascending and descending connections that are distributed with the medial forebrain bundle to the hypothalamus and rostral midbrain; in addition, it gives rise to an unusually well-defined projection to field CA2 of the hippocampus and to a narrow zone overlying the outer part of the granule cell layer and the adjoining part of the molecular layer of the dentate gyrus. We have not been able to distinguish the connections of the posterior hypothalamic nucleus from those of the caudal part of the lateral hypothalamic area: they both appear to contribute substantially to the ascending components of the medial forebrain bundle, and through its descending projection to the tegmental fields of the midbrain, the nucleus centralis superior of the raphe complex, the locus coeruleus, and the central gray as far caudally as the facial nerve. Their further projections to the spinal cord were not examined. Viewed broadly, and in the light of previous work, our observations confirm, once again, the constancy of the connections of the hypothalamus in the mammalian brain, and the pivotal position that the posterior hypothalamus occupies in the elaborate system of connections that links the limbic areas of the forebrain with the complex of structures that Nauta has aptly designated the "midbrain limbic region."

A 14C-2-deoxyglucose analysis of the neural pathways of the limbic forebrain in the rat: II. The hypothalamus.

An attempt was made to characterize the nature of the functional organization of the hypothalamus by observing the patterns of uptake of 14C-2-deoxyglucose (2DG) following electrical stimulation of different regions within the preoptico-hypothalamus in the rat. The experimental paradigm consisted of electrical brain stimulation delivered continuously for periods of 30 sec on and 30 sec off for 45 minutes following injection of 2DG. Brains were removed and processed for autoradiography. Activation of the medial forebrain bundle was noted following stimulation of the nucleus accumbens and lateral preoptico-hypothalamus. Activated fibers could be followed only in a caudal direction through the medial forebrain bundle and into the ventral tegmental area as a result of nucleus accumbens stimulation. Stimulation of the lateral preoptic region or of the anterior half of lateral hypothalamus produced activation of the lateral septal nucleus, lateral habenular nucleus, perifornical region, midline thalamus and ventral tegmental area. Since stimulation of the perifornical hypothalamus significantly activated the rostro-caudal extent of the midbrain cental gray, it is suggested that impulses from the lateral hypothalamus reach the lower brainstem via its connections with the perifornical hypothalamus. Ventromedial hypothalamic stimulation activated only the lateral septal nucleus, cortico-medial amygdala and medial preoptico-hypothalamus, while medial preoptico-hypothalamic stimulation resulted in increased 2DG uptake in the midbrain central gray, thus suggesting that medial hypothalamic impulses reach the brainstem by first ascending to the level of the preoptico-hypothalamus. Mammillary body stimulation orthodromically activated fibers in the mammillothalamic and mammillotegmental tracts and antidromically fibers in the fornix for a short distance.

The medial forebrain bundle of the rat. II. An autoradiographic study of the topography of the major descending and ascending components.

The medial forebrain bundle (MFB) is a complex fiber system that courses through and partly arises and partly terminates within the lateral preoptic and lateral hypothalamic areas. It consists mainly of thin fibers and may be comprised of as many as 50 descending and ascending components of varying lengths and of different origins and/or destinations (Nieuwenhuys et al., '82). With the aid of an an atlas of the MFB and the surrounding brain areas in the rat presented in the preceding paper (Nieuwenhuys et al., '82), the position and topographic relationships of some 21 components of the bundle have been analyzed in detail, in brains that had been prepared for autoradiography following injections of tritiated amino acids into a number of structures that are known to contribute fibers to the MFB. From this analysis it is clear that most of the labeled components occupy specific and rather constant positions within the MFB. For example, the ascending components are largely confined to the dorsal half of the bundle; those arising from the medial preoptic area and the various hypothalamic nuclei are distributed rather diffusely over much of the MFB; and the descending components that arise from the olfactory tubercle and the magnocellular preoptic nucleus are confined to restricted parts of the bundle. These findings indicate that the neurons which occupy different parts of the lateral hypothalamic area probably receive distinctive inputs, and to a first approximation these are likely to be determined principally by their position within the MFB.

The medial forebrain bundle of the rat. I. General introduction.

This paper is the first of a projected series of studies on the structure and composition of the medial forebrain bundle (MFB) of the rat and the relations of this fiber system to its bed nucleus, the lateral hypothalamic area. The first part of the paper comprises an extensive review of literature on the MFB from its discovery by Ganser in 1882 to the present. This review serves as the basis for an evaluation of our present-day knowledge of the organization of the MFB, which is presented in the second part of this paper. Despite the wealth of information available on the origins and sites of termination of the axons that constitute the MFB, surprisingly little attention has been given to the bundle itself, to its topographic boundaries, its fiber composition, or to the spatial arrangement of its constituent components. These features of the MFB as it extends through the lateral preoptic and lateral hypothalamic areas have been analyzed in normal Klüver-Barrera- and Bodian-stained material. From this analysis, a detailed atlas of the MFB and some of the surrounding structures has been prepared. This atlas, which forms the third section of this paper, illustrates the appearance and organization of the MFB at ten equidistant levels through the lateral preoptic and lateral hypothalamic continuum.