Ventral Tegmental Nucleus Of Gudden Research Articles

Turning a Negative into a Positive: Ascending GABAergic Control of Cortical Activation and Arousal.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. Recent technological advances have illuminated the role of GABAergic neurons in control of cortical arousal and sleep. Sleep-promoting GABAergic neurons in the preoptic hypothalamus are well-known. Less well-appreciated are GABAergic projection neurons in the brainstem, midbrain, hypothalamus, and basal forebrain, which paradoxically promote arousal and fast electroencephalographic (EEG) rhythms. Thus, GABA is not purely a sleep-promoting neurotransmitter. GABAergic projection neurons in the brainstem nucleus incertus and ventral tegmental nucleus of Gudden promote theta (4–8 Hz) rhythms. Ventral tegmental area GABAergic neurons, neighboring midbrain dopamine neurons, project to the frontal cortex and nucleus accumbens. They discharge faster during cortical arousal and regulate reward. Thalamic reticular nucleus GABAergic neurons initiate sleep spindles in non-REM sleep. In addition, however, during wakefulness, they tonically regulate the activity of thalamocortical neurons. Other GABAergic inputs to the thalamus arising in the globus pallidus pars interna, substantia nigra pars reticulata, zona incerta, and basal forebrain regulate motor activity, arousal, attention, and sensory transmission. Several subpopulations of cortically projecting GABAergic neurons in the basal forebrain project to the thalamus and neocortex and preferentially promote cortical gamma-band (30–80 Hz) activity and wakefulness. Unlike sleep-active GABAergic neurons, these ascending GABAergic neurons are fast-firing neurons which disinhibit and synchronize the activity of their forebrain targets, promoting the fast EEG rhythms typical of conscious states. They are prominent targets of GABAergic hypnotic agents. Understanding the properties of ascending GABAergic neurons may lead to novel treatments for diseases involving disorders of cortical activation and wakefulness.

Projections from Gudden's tegmental nuclei to the mammillary body region in the cynomolgus monkey (Macaca fascicularis)

Gudden's tegmental nuclei provide major inputs to the rodent mammillary bodies, where they are thought to be important for learning and navigation. Comparable projections have yet to be described in the primate brain, where part of the problem has been in effectively delineating these nuclei. Immunohistochemical staining of tissue from a series of macaque monkeys (Macaca mulatta) showed that cells in the region of both the ventral and dorsal tegmental nuclei selectively stain for parvalbumin, thus helping to reveal these nuclei. These same tegmental nuclei were not selectively revealed when tissue was stained for SMI32, acetylcholinesterase, calbindin, or calretinin. In a parallel study, horseradish peroxidase was injected into the mammillary bodies of five cynomolgus monkeys (Macaca fascicularis). Retrogradely labeled neurons were consistently found in the three subdivisions of the ventral tegmental nucleus of Gudden, which are located immediately below, within, and above the medial longitudinal fasciculus. Further projections to the mammillary body region arose from cells in the anterior tegmental nucleus, which appears to be a rostral continuation of the infrafascicular part of the ventral tegmental nucleus. In the dorsal tegmental nucleus of Gudden, labeled cells were most evident when the tracer injection was more laterally placed in the mammillary bodies, consistent with a projection to the lateral mammillary nucleus. The present study not only demonstrates that the primate mammillary bodies receive parallel inputs from the dorsal and ventral tegmental nuclei of Gudden, but also helps to confirm the extent of these poorly distinguished nuclei in the monkey brain.

Re-evaluating the role of the mammillary bodies in memory

Although the mammillary bodies were among the first brain regions to be implicated in amnesia, the functional importance of this structure for memory has been questioned over the intervening years. Recent patient studies have, however, re-established the mammillary bodies, and their projections to the anterior thalamus via the mammillothalamic tract, as being crucial for recollective memory. Complementary animal research has also made substantial advances in recent years by determining the electrophysiological, neurochemical, anatomical and functional properties of the mammillary bodies. Mammillary body and mammillothalamic tract lesions in rats impair performance on a number of spatial memory tasks and these deficits are consistent with impoverished spatial encoding. The mammillary bodies have traditionally been considered a hippocampal relay which is consistent with the equivalent deficits seen following lesions of the mammillary bodies or their major efferents, the mammillothalamic tract. However, recent findings suggest that the mammillary bodies may have a role in memory that is independent of their hippocampal formation afferents; instead, the ventral tegmental nucleus of Gudden could be providing critical mammillary body inputs needed to support mnemonic processes. Finally, it is now apparent that the medial and lateral mammillary nuclei should be considered separately and initial research indicates that the medial mammillary nucleus is predominantly responsible for the spatial memory deficits following mammillary body lesions in rats.

Gudden's ventral tegmental nucleus is vital for memory: re-evaluating diencephalic inputs for amnesia

Mammillary body atrophy is present in a number of neurological conditions and recent clinical findings highlight the importance of these nuclei for memory. While most accounts of diencephalic amnesia emphasize the functional importance of the hippocampal projections to the mammillary bodies, the present study tested the importance of the other major input to the mammillary bodies, the projections from the ventral tegmental nucleus of Gudden (VTNg). Although the VTNg, and its projections to the mammillary bodies, is present across species, the size and location of this structure has made it an extremely difficult structure to assess in primates. The effects of selective, neurotoxic lesions of the VTNg were, therefore, assessed in rats. The animals with these lesions were impaired on a series of spatial learning tasks, namely delayed-matching-to-place in the water maze, T-maze alternation and working memory in the radial arm maze. Normal performance on these tasks is dependent on those brain structures (e.g. hippocampus and mammillary bodies) that are now assumed to cause anterograde amnesia when damaged in humans. In contrast, the same rats with ventral tegmental nucleus lesions performed normally on two control tasks: the acquisition and subsequent reversal of an egocentric discrimination task and a visually cued task in the water maze. This study provides the first clear evidence that the VTNg is critical for memory, and consequently indicates that diencephalic-hippocampal models of memory should be extended to incorporate the limbic midbrain.

Gudden’s dorsal tegmental nucleus is activated in carbachol-induced active (REM) sleep and active wakefulness

Previous studies have shown that GABAergic processes in the ponto-mesencephalic region of the brainstem are involved in the generation of wakefulness and active sleep (AS). The dorsal and ventral tegmental nuclei of Gudden (DTN and VTN, respectively) are known to contain a large population of GABAergic neurons. In the present study, utilizing Fos immunoreactivity as a marker of neuronal activity, it was determined that GABAergic DTN pars dorsalis neurons are active during active wakefulness and AS induced by carbachol, but not during quiet wakefulness or quiet sleep. In contrast, no differences in the number of Fos immunoreactive neurons were observed in the DTN pars ventralis and VTN across behavioral states.

Sleep-related increase in activity of mesopontine neurons in old rats.

Relationships between age-related changes in sleep patterns and neuronal activity have received scant attention. In the present study, reticularis pontis oralis (RPO) and ventral tegmental nucleus of Gudden (VTN) neurons were recorded in unanesthetized restrained young (3 months) and old (23 months) Sprague-Dawley rats during wakefulness (W), slow wave sleep (SWS) and rapid eye movement (REM) sleep. All RPO neurons displayed a tonic activity. Firing rates were similar during W in young and old rats. In contrast, firing rates were higher during SWS in old rats (P < 0.001). In both young and old rats, firing rates increased significantly during REM sleep as compared to W and SWS but this increase was markedly greater in old rats. Neurons recorded from VTN displayed bursting activity at theta frequencies during W and REM sleep. The frequency of VTN bursting neurons was higher during REM sleep as compared to W in both groups of age. This difference was significantly more pronounced in old as compared to young rats (P < 0.001). Sleep-related hyperactivity of pontine neurons is discussed in terms of a possible deficit in inhibitory processes in old rats.

Localization of amino acids, neuropeptides and cholinergic neurotransmitter markers in identified projections from the mesencephalic tegmentum to the mammillary nuclei of the rat

Retrograde labelling has been combined with immunohistochemistry to localize neurons containing GABA, glutamate, choline acetyltransferase, leu-enkephalin, neurotensin and substance P-like immunoreactivity in the projection pathways from the midbrain tegmental nuclei to the mammillary nuclei in the rat. Injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the medial mammillary nucleus resulted in retrogradely labelled neurons in the ventral tegmental nucleus of Gudden, whereas injections into the lateral mammillary nucleus resulted in large numbers of retrogradely labelled neurons in the ipsilateral dorsal tegmental nucleus of Gudden and in the laterodorsal tegmental nucleus. In the ventral tegmental nucleus, moderate to small numbers of retrogradely labelled neurons were also immunolabelled for GABA and approximately ten to 18 WGA-HRP-labelled neurons per section were immunoreactive for leu-enkephalin. In addition, small numbers of WGA-HRP-labelled neurons in the principal subnucleus of the ventral tegmental nucleus were immunoreactive for Glu whereas small numbers of retrogradely labelled neurons in the compact subnucleus of the central superior nucleus displayed neurotensin-like immunoreactivity. In the ventral subnucleus of the dorsal tegmental nucleus, moderate to small numbers of retrogradely labelled neurons were also GABA-immunoreactive and approximately ten to 14 WGA-HRP labelled neurons per section were immunoreactive for leu-enkephalin. The ventral subnucleus of the dorsal tegmental nucleus also contained small numbers of retrogradely labelled neurons that displayed either glutamate or substance P-like immunoreactivity. In addition, moderate to small numbers of WGA-HRP-labelled neurons (five to 20 per section) in the laterodorsal tegmental nucleus were immunoreactive for choline acetyltransferase. These results are compatible with the possibility that tegmentomammillary projection neurons use several different neurochemicals as neurotransmitter(s) and/or neuromodulator(s).

Fos-like immunoreactivity in the mamillary body and thalamus following injections of muscimol into the ventral tegmental nucleus of Gudden in the rat

In many neurons, increased rates of firing are accompanied by expression of the proto-oncoprotein Fos. The current study examined Fos-like immunoreactivity in the mamillary body and the anterior thalamus following unilateral injections of the inhibitory GABA-A agonist muscimol into the ventral tegmental nucleus of Gudden (VTN). These injections resulted in a marked increase in Fos-like immunoreactivity ipsilaterally in both the medial mamillary nucleus and in its principle thalamic projection targets, the anteroventral and anteromedial thalamic nuclei. Since the projection from the VTN to the mamillary body has been shown to contain a substantial GABAergic component, these results are likely to reflect a disinhibition of mamillothalamic circuitry resulting from suppression of tonic inhibitory inputs arising in the VTN.

Evidence for GABAergic projections from the tegmental nuclei of Gudden to the mammillary body in the rat

Immunochemical studies have demonstrated the presence of large numbers of cells immunoreactive for glutamic acid decarboxylase (GAD) within the dorsal and ventral tegmental nuclei of gudden. Following injections of Fluoro-Gold into the medial mammillary nucleus, a substantial proportion of the retrogradely labeled neurons within the ventral tegmental nucleus displayed GAD-like immunoreactivity. Conversely, electrolytic or excitotoxic lesions of the ventral tegmental nucleus produced a large decrease in the number of fibers and terminals immunoreactive for GAD within the medial mammillary nucleus. In contrast, electrolytic lesions of the dorsal tegmental nucleus were found to produced a large decrease in GAD-like immunoreactivity which was restricted to the lateral mammillary nucleus. Control lesions placed caudal to the dorsal tegmental nucleus were without effect. These findings suggest that the dorsal and ventral nuclei send a substantial, topographically organized, GABAergic input to the mammillary body.

Regional distribution of the cells expressing glycine receptor β subunit mRNA in the rat brain

The expression of mRNA of the β subunit of the glycine receptor was investigated in the rat by in situ hybridization histochemistry using an oligonucleotide probe specific to the sequence of the β subunit. Neurons expressing β subunit mRNA were widely and abundantly distributed in the rat brain from the olfactory bulb to the spinal cord. The pattern of distribution of cells containing β subunit mRNA in the lower brainstem was very similar to that of cells containing a 1 subunit mRNA. In addition, β subunit mRNA was strongly expressed by the neurons of the cerebral cortex, hippocampal formation and diencephalon as well as by the Purkinje cells where a 1 subunit mRNA expression is rare. These findings indicated that the glycine receptor is heterogeneous. The sites where strong labeling was noted were as follows. In the forebrain and diencephalon, strongly labeled neurons were abundant in the olfactory region, hippocampal formation, cerebral cortex, and thalamus. In the hippocampal formation, neurons in the subiculum, pyramidal cells in Ammon's horn, and neurons in the polymorphic layer of the dentate gyrus were strongly labeled. In the thalamus, the anterodorsal, reticular, parafascicular, and the subthalamic nuclei were strongly labeled. In the brainstem, the red nucleus, almost all of the motor neurons in the cranial motor nuclei innervating striated muscles, the trigeminal mesencephalic nucleus, the ventral tegmental nucleus of Gudden, and the pontine nucleus were strongly labeled. In the cerebellum, Purkinje cells in the Purkinje cell layer and all of the cerebellar nuclei were strongly labeled.

Quantitative and ultrastructural study of ascending projections to the medial mammillary nucleus in the rat

We analyzed the termination pattern of axons from the superior central nucleus and the ventral tegmental nucleus of Gudden within the medial mammillary nucleus (MM) in the rat. The neuropil of the MM consists of two classes of terminals, that is, terminals containing round synaptic vesicles and forming asymmetric synaptic contact, and terminals containing pleomorphic synaptic vesicles and forming symmetric synaptic contact. The number of axodendritic terminals with round vesicles is almost equal to that of terminals with pleomorphic vesicles. Almost all axosomatic terminals contain pleomorphic vesicles with symmetric synaptic contact. Injection of WGA-HRP into the central part of the superior central nucleus permitted ultrastructural recognition of many anterogradely labeled terminals within the median region of MM. The labeled terminals contacted mainly intermediate (1-2 microns diameter) and proximal dendrites (more than 2 microns diameter) as well as the neuronal somata. Serial ultrathin sections of neurons of the median region of the MM revealed that 37% of the axosomatic terminals were labeled anterogradely. The pars compacta of the superior central nucleus had reciprocal connections with the median region of MM. The axon terminals from this nucleus occupied 53% of axosomatic terminals, and contacted mainly intermediate dendrites. Following injection of WGA-HRP into the ventral tegmental nucleus, many labeled terminals were found in the medial and lateral regions of MM. They contacted mainly intermediate dendrites as well as neuronal somata. In the medial region, 78% of axosomatic terminals contacting retrogradely labeled neurons were labeled anterogradely. All labeled terminals from these nuclei contained pleomorphic vesicles, and made symmetric synaptic contact.

Localization of GABA A-receptor α 1 subunit mRNA-containing neurons in the lower brainstem of the rat

The localization of γ-aminobutyric acid-A (GABA A) receptors (GABA A-R) in the lower brainstem of the rat was examined by means of in situ hybridization histochemistry using an oligonucleotide probe to the sequence of the α 1 subunit (GABA A-R α 1). Strongly labeled nucleus, were found in the cranial motor nuclei, the dorsal motor nucleus of the vagus, reticular formation (large neurons), lateral vestibular nucleus, dorsal nucleus of the lateral lemniscus, central nucleus of the inferior colliculus, intermediate and white layers of the superior colliculus, red nucleus and substantia nigra. In addition, moderately labeled cells were abundant in the nucleus of the solitary tract, medial and inferior vestibular nuclei, parabrachial area, dorsal and ventral tegmental nuclei of Gudden, central gray matter, ventral nucleus of the lateral lemniscus, and reticular formation (small neurons). This study has therefore revealed some of the target neurons of GABA-containing fibers in the lower brainstem.

Ultrastructure of the mammillotegmental projections to the ventral tegmental nucleus of gudden in the rat

This study examines the termination pattern of axons from the medial mammillary nucleus within the ventral tegmental nucleus of Gudden (TV) in rats by using anterograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) and visualized with tetramethylbenzidine. The neuropil of TV contains three classes of axodendritic terminals, that is, terminals containing round, flat, and pleomorphic synaptic vesicles. These types make up 55.6%, 26.1%, and 18.3%, respectively, of all normal axodendritic terminals. Injection of WGA-HRP into the medial mammillary nucleus permits ultrastructural recognition of anterogradely labeled terminals within the TV. More than 80% of the labeled terminals contain round synaptic vesicles and form asymmetric synaptic contacts, whereas about 16% contain flat synaptic vesicles with symmetric synaptic contacts. There are a few labeled terminals with pleomorphic vesicles and only a few axosomatic terminals. Almost all labeled terminals are small, having diameters of less than 1.5 microns. Compared with the distributions of normal and labeled terminals with round vesicles, there is an increase of the percentage of labeled terminals with round vesicles on the intermediate dendrites (1-2 microns diameter) and a decrease on the distal dendrites (less than 1 micron diameter). Anterogradely labeled axon terminals often contact retrogradely labeled dendrites. These results suggest that the medial mammillary neurons send mainly excitatory as well as a few inhibitory inputs to the dendrites of TV and have direct reciprocal contacts with the TV neurons.

Retrograde double‐labeling study of the marnmillothalamic and the mammillotegmental projections in the rat

Collateral axonal branching from the medial or lateral mammillary nuclei to the anterior thalamus, Gudden's tegmental nuclei, the nucleus reticularis tegmenti pontis, and the medial pontine nucleus was studied using the fluorescent retrograde double-labeling method. One day after injection of Fast Blue into the anterior thalamic nuclei or Gudden's tegmental nuclei, Nuclear Yellow was injected into Gudden's tegmental nuclei or the nucleus reticularis tegmenti pontis and the medial pontine nucleus. Following 1 day survival, single- and double-labeled neurons were examined in the mammillary nuclei. The lateral mammillary nucleus contains neurons whose collateral fibers project to both the dorsal tegmental nucleus of Gudden and the ipsilateral or contralateral anterodorsal thalamic nucleus, to both the medial pontine nucleus and the anterodorsal thalamic nucleus, and to both the dorsal tegmental nucleus of Gudden and the medial pontine nucleus. The pars medianus and pars medialis of the medial mammillary nucleus contain neurons whose collateral fibers project to both the anteromedial thalamic nucleus and the ventral tegmental nucleus of Gudden, to both the anteromedial thalamic nucleus and the medial part of the nucleus reticularis tegmenti pontis, and to both the ventral tegmental nucleus of Gudden and the medial part of the nucleus reticularis tegmenti pontis. The dorsal half of the pars posterior of the medial mammillary nucleus contains a few neurons whose collateral fibers project to both the anteromedial thalamic nucleus and the rostral part of the ventral tegmental nucleus of Gudden, and to both the caudal part of the anteroventral thalamic nucleus and the rostral part of the ventral tegmental nucleus of Gudden, while the pars lateralis of the medial mammillary nucleus contains no double-labeled neurons and projects only to the anteroventral thalamic nucleus.

Afferent and efferent connections of the cholinoceptive medial pontine reticular formation (region of the ventral tegmental nucleus) in the cat

Following minor concussive brain injury when there is an otherwise general suppression of CNS activity, the ventral tegmental nucleus of Gudden (VTN) demonstrates increased functional activity (32). Electrical or pharmacological activation of a cholinoceptive region in this same general area of the medial pontine tegmentum contributes to certain components of reversible traumatic unconsciousness, including postural atonia (31, 32, 45). Therefore, in an effort to examine the neuroanatomical basis of the behavioral suppression associated with a reversible traumatic unconsciousness, the afferent and efferent connections of the VTN and putative cholinoceptive medial pontine reticular formation (cmPRF) were studied in the cat using the retrograde horseradish peroxidase (HRP), HRP/choline acetyltransferase (ChAT) double-labeling immunohistochemistry, and anterograde HRP and autoradiographic techniques. Based upon retrograde HRP labeling, the principal afferents to the VTN region of the cmPRF originated from the medial and lateral mammillary nuclei, and lateral habenular nucleus, and to a lesser extent from the interpeduncular nucleus, lateral hypothalamus, dorsal tegmental nucleus, superior central nucleus, and contralateral nucleus reticularis pontis caudalis. Other afferents, which were thought to have been labeled through spread of HRP into the medial longitudinal fasciculus (MLF), adjacent paramedian pontine reticular formation, or uptake by transected fibers descending to the inferior olive, included the nucleus of Darkschewitsch, interstitial nucleus of Cajal, zona incerta, prerubral fields of Forel, deep superior colliculus, nucleus of the posterior commissure, nucleus cuneiformis, ventral periaqueductal gray, vestibular complex, perihypoglossal complex, and deep cerebellar nuclei. In HRP/ChAT double labeling studies, only a very small number of cholinergic VTN afferent neurons were found in the medial parabrachial region of the dorsolateral pontine tegmentum, although the pedunculopontine and laterodorsal tegmental nuclei contained numerous single-labeled ChAT-positive cells. Anterograde HRP and autoradiographic findings demonstrated that the VTN gave rise almost exclusively to ascending projections, which largely followed the course of the mammillary peduncle (16, 21) and medial forebrain bundle, or the tegmentopeduncular tract (4). The majority of fibers ascended to terminate in the medial and lateral mammillary nuclei, interpeduncular complex (especially paramedian subnucleus), ventral tegmental area, lateral hypothalamus, and the medial septum in the basal forebrain. Labeling that joined the mammillothalamic tract to terminate in the anterior nuclear complex of the thalamus was thought to occur transneuronally. Some projections were also observed to nucleus reticularis pontis oralis and caudalis, superior central nucleus, and dorsal tegmental nucleus adjacent to the VTN. Only when the injections involved more extensive portions of the rostral mPRF were projections to the intralaminar complex and reticular nucleus of the thalamus observed. Only meager descending projections were observed to the nucleus reticularis pontis caudalis and nucleus reticularis gigantocellularis of the rostral medulla, and none were observed to the spinal cord. While no functional significance could be attributed to the predominantly ascending limbic connections of the VTN, the lack of descending spinal connections, and the failure of these studies to find a major cholinergic input to a region purported to be the cholinoceptive pontine inhibitory area (CPIA), are discussed in relation to the possible neuroanatomical bases of the complex functional roles of the medial pontine tegmentum in the etiology of behavioral consequences following traumatic brain injury. Taken together with previous reports, the study suggests that the spinal-projecting portion of the CPIA responsible for muscular atonia is located in the medial brainstem tegmentum caudal to the VTN.

Fine structural survey of Gudden's tegmental nuclei in the rat: cytology and axosomatic synapses.

The fine structure of neuronal somata and axosomatic synapses in each subnucleus of Gudden's tegmental nuclei was studied by use of electron microscopy. The pars principalis of the ventral tegmental nucleus of Gudden (TVP) is composed of oblong or triangular, medium sized neurons (11.8 x 22.6 microns, 211.4 microns 2) containing many mitochondria, lysosomes, Golgi apparatus, and rough endoplasmic reticulum composing Nissl bodies. The light oval nucleus with a prominent nucleolus is centrally situated, and indentations of its nuclear envelope are recognized in all neurons. The neuron in the pars ventralis of the dorsal tegmental nucleus of Gudden (TDV) is similar to that in the TVP, but its average size is significantly smaller (10.0 x 18.8 microns, 151.4 microns 2), and its organelles are also less well developed. The pars dorsalis of the dorsal tegmental nucleus of Gudden (TDD) is composed of spindle shaped, small neurons (6.9 x 16.2 microns, 85.1 microns 2) characterized by their irregular shaped nucleus with its invaginated envelope. These neurons have a thin rim of cytoplasm, poorly developed organelles and no Nissl bodies. The average number of axosomatic terminals in a sectional plane is 9.9 in the TVP, 9.6 in the TDV and 2.6 in the TDD, and the bouton covering ratio is 24.3% in the TVP, 26.5% in the TDV and 7.4% in the TDD. The respective percentages of round, flat and pleomorphic type axosomatic terminals were estimated, and the flat type terminals were found to be dominant in the TVP, the pleomorphic type terminals in the TDV, and the round type terminals in the TDD.

Localization of chick retinal 24,000 dalton protein (visinin)-like immunoreactivity in the rat lower brain stem

The distribution of visinin, a 24,000 dalton peptide, in the lower brain stem of the rat was examined by means of an indirect immunofluorescent method. Visinin-immunoreactive structures were found to be unevenly distributed only in the neuronal elements. The following neuronal systems were strongly labeled by the antiserum; the Purkinje cell system, mammillotegmental system, habenulointerpeduncular system, the second layer of the superior colliculus, ventral tegmental area, substantia nigra pars lateralis, area medial to the medial geniculate body, parabrachial area, dorsal and ventral nuclei of the lateral lemniscus, pontine reticular formation just medial to the trigeminal principal nucleus, superior olivary nucleus, solitarii nucleus, external layer of the inferior colliculus and spinal trigeminal nucleus. The densities of the labeled fibers in these areas paralleled those of the labeled cells. In addition, highly dense visinin-immunoreactive fiber plexuses were seen in the zona compacta of the substantia nigra, lateral portion of the interpeduncular nucleus, ventral tegmental nucleus of Gudden and vestibular nucleus.

Cholecystokinin-8-like immunoreactive neuron pathway from the supramammillary region to the ventral tegmental nucleus of Gudden of the rat

The existence of a pathway from the supramammillary region (SM) to the ventral tegmental nucleus of Gudden (NTV) containing cholecystokinin-8 (CCK)-like immunoreactive (CCKI) structures was demonstrated by experimental manipulations in the rat. Destruction of the SM resulted in the disappearance of CCKI fibers in the NTV.

Comparative anatomical study of the tegmentomammillary projections in some mammals: A horseradish peroxidase study

Mammillary projections from each subnuclei of Gudden's tegmental nuclei were investigated by retrograde transport of horseradish peroxidase (HRP) in the cat, rat, guinea pig, golden hamster and house shrew ( Suncus murinus, Insectivora). The dorsal tegmental nucleus of Gudden (TD) is composed of the pars dorsalis (TDD) and the pars ventralis (TDV) in the cat, rat, guinea pig, and golden hamster, but the TD of the house shrew can not be divided. The ventral tegmental nucleus of Gudden (TV) is composed of the pars principalis (TVP) and the pars suprafascicularis (TVS) in the golden hamster and house shrew, but the TVS is not recognized in the cat, rat and guinea pig. The TDV projects to the lateral mammillary nucleus, and the TVP projects to the medial mammillary nucleus ipsilaterally in the cat, rat, guinea pig and golden hamster. The TVS of the golden hamster projects to the medial mammillary nucleus. The TVP and TVS of the house shrew project to the medial mammillary nucleus, and the TVS also to the lateral mammillary nucleus. In addition, the pars compacta of the nucleus centralis superior projects to the medial mammillary nucleus in the rat, guinea pig and golden hamster. However, the TDD sends no fibers to the mammillary nuclei in these 5 species of mammals.

Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons.

The distribution of the afferents to the rat's prefrontal cortex originating in the thalamic mediodorsal nucleus and the amygdala was investigated with two fluorescent tracers. Special emphasis was laid on detecting the loci of neurons which project via axonal collaterals into both lateral and medial portions of the prefrontal cortex. It was found that a high number of neurons of the anterior portion of the basolateral amygdaloid nucleus terminate via collaterals in both the medial and lateral subfields of the prefrontal cortex. On the other hand, only a small number of mediodorsal thalamic cells were found to project to both sides of the prefrontal hemisphere via bifurcating axonal collaterals. These cells were situated exclusively in the lateral part of the medial segment of the mediodorsal nucleus. The majority of both thalamic and amygdaloid neurons with bifurcating axons originate from subregions whose cells innervate primarily the medial prefrontal cortex. In brain-stem, neurons of the nucleus raphé dorsalis also project via collaterals to the medial and lateral prefrontal regions. Furthermore, neurons of the dorsal and ventral premamillary nuclei, the lateral mamillary nucleus, the ventral tegmental area of Tsai, and the ventral tegmental nucleus of Gudden were found to project to the medial prefrontal cortex. Our results indicate a differential collateral organization of thalamic and amygdaloid afferents to prefrontal cortical fields. The anterior basolateral amygdala (which innervates via collaterals both the medial and lateral prefrontal subfields) may add a common input to either subfield, such as information on the significance of incoming stimuli to the animal's behavior, while the mediodorsal nucleus (whose segments are principally connected to only one prefrontal subfield) may add segment-specific information, for example, of a spatial-cognitive nature for the lateral segment and of an emotional nature for the central and medial segments. The existence of a basolateral limbic circuit, composed of the amygdala, the thalamic mediodorsal nucleus, and the prefrontal cortex, is confirmed and knowledge on its interconnectivity is extended. From an anatomical point of view these data provide arguments for both unitary and diverging functions of the prefrontal cortex.