Efferent projections from the region of the medial zona incerta containing A13 dopaminergic neurons: a PHA-L anterograde tract-tracing study in the rat

Potential efferent projections of A₁₃ dopaminergic (DA) neurons were identified in the present study by examining the distribution of labelled fibers following iontophoretic injection of the anterogradely transported lectinPhaseolus vulgaris leucoagglutinin (PHA-L) into the medial zona incerta (MZI), the region of the diencephalon containing A₁₃ DA neuronal perikarya. One week after injection, PHA-L labelled fibers were found throughout the brain with the heaviest labelling occurring ipsilateral to the injection site in the anterior hypothalamic area, lateral hypothalamus, lateral preoptic area, horizontal diagonal band of Broca, and parvocellular region of the paraventricular nucleus. Moderate labelling was observed in the ipsilateral median preoptic nucleus, lateral septum, lateral aspect of the bed nucleus of the stria terminalis, and central nucleus of the amygdala. Moderate labelling was also found in the contralateral MZI and parvocellular region of the paraventricular nucleus. Light labelling was detected in the ipsilateral medial preoptic area, supraoptic nucleus, ventromedial nucleus, arcuate nucleus, vertical limb of the diagonal band of Broca, and in the contralateral lateral hypothalamus. Few immunopositive fibers were present in the dorsomedial nucleus of the hypothalamus or the magnocellular region of the paraventricular nucleus. These results reveal that neurons located in the MZI (possibly A₁₃ DA neurons) have ipsilateral efferent axonal projections to a variety of brain regions including the lateral hypothalamus, lateral preoptic area, and the limbic structures at the diencephalic-telencephalic juncture.     

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.     

The efferent connections of the pupillary constriction area in the rat medial frontal cortex

This study investigated, in the rat, the efferent projections of the pupillary constriction area, which is located within the medial frontal cortex. In order to identify the location of the pupillary constriction area, in preliminary experiments the medial frontal cortex was microstimulated. Intracortical microstimulation elicited pupillary constriction in a thin strip of cortex near the interhemispheric fissure and bordering the frontal eye field and vibrissae area of the somatomotor cortex. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in the pupillary constriction area. In these cases, anterogradely labelled fibres and terminal-like elements were found in both hemispheres. The densest labeling was seen in several areas of the injected hemisphere, where labeled fibers prevailed in the secondary visual cortex. Dense labeled fibers were also found in the retrosplenial and cingulate cortex. In the thalamus, labeled fibers were seen in the intralaminar nuclei and posterior nuclear group. In the midbrain and pons, labeled fibers were located in the anterior pretectal area, superior colliculus and in the dorsolateral portion of the central gray. Contralaterally to the injection site, labeled fibers were distributed in the homotopic region. These findings led us to assume that, in the medial frontal cortex of the rat, besides controlling pupillary constriction, the pupillary constriction area may also be involved in controlling orientation and exploring behavior.     

Efferent connections of the prelimbic (area 32) and the infralimbic (area 25) cortices: an anterograde tracing study in the cat

The projections from the caudal part of the medial frontal cortex, encompassing the prelimbic area (PL) and the infralimbic area (IL) (Brodmann's areas 32 and 25, respectively), were studied in the cat with the anterograde autoradiographic tracing technique. The results indicate that the projection fields of IL, in contrast to those of PL, are restricted almost exclusively to limbic structures. Whereas the major thalamic projections from PL reach the mediodorsal, anteromedial, and ventromedial nuclei, the medial part of the lateral posterior nucleus, and the parataenial and reticular nuclei, and weak projections from this area are directed to the nucleus reuniens and other midline nuclei, the nucleus reuniens is the major thalamic termination field of fibers arising from IL. Cortical areas that are reached by fibers originating in PL and, to a lesser degree, also in IL, include more rostral prefrontal areas (areas 8, 6, and 12), the agranular insular, and the rostral perirhinal cortices. In contrast, cortical areas that are more strongly related to IL include the cingulate, retrosplenial, caudal entorhinal, and perirhinal cortices and the subiculum of the hippocampal formation. Another prominent output of PL concerns projections to an extensive medial part of the caudate nucleus and the ventral striatum, whereas fibers from IL only distribute most ventrally in the striatum. In the amygdaloid complex, fibers from PL were found to reach the basolateral, basomedial, and central nuclei, and fibers from IL to distribute to the medial and central nuclei. PL furthermore projects to the claustrum and the endopiriform nucleus. Other structures in the basal forebrain, including the medial septum, the nuclei of the diagonal band, the preoptic area, and the lateral and dorsal hypothalamus are densely innervated by IL and only sparsely by PL. With respect to more caudal parts of the brainstem, projections from PL and IL appeared to be essentially similar. They reach the ventral tegmental area, the periaqueductal gray, the parabrachial nucleus, and in cases of PL injections were followed as far caudally as the pons.     

Associational projections of the anterior midline cortex in the rat: intracingulate and retrosplenial connections

Past studies indicate that distinct areas of anterior midline cortex in the rat contribute to diverse functions, such as autonomic nervous system regulation and learning, but the anatomical substrate for these functions has not been fully elucidated. The present study characterizes the associational connections within the midline cortex of the rat by using the anterograde transport of Phaseolus vulgaris leucoagglutinin and Fluororuby. The prelimbic area and the rostral part of the anterior cingulate area (both dorsal and ventral subdivisions) are extensively interconnected with each other. In addition, the caudal half of anterior cingulate cortex has extensive projections to precentral medial cortex and caudally directed projections to retrosplenial cortex. Other cortical areas within anterior midline cortex have relatively limited cortical–cortical projections. The infralimbic, dorsal peduncular, and medial precentral cortices have dense intrinsic projections, but have either very limited or no projections to other areas in the anterior midline cortex. Although it has been suggested that cortical–cortical projections from anterior cingulate cortex and prelimbic cortex to infralimbic cortex may be important for linking learning processes with an autonomic nervous system response, the paucity of direct projections between these areas calls this hypothesis into question. Conversely, the results suggest that the anterior midline cortex contains two regions that are functionally and connectionally distinct.     

Amygdala input to medial prefrontal cortex (mPFC) in the rat: A light and electron microscope study

This paper describes the termination pattern and synaptic connectivity of the pathway from the basolateral nucleus of the amygdala (BLA) to the medial prefrontal cortex (mPFC; areas 25, 32, and 24b) of the rat. Discrete injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) were made in the BLA and detailed light microscopical observations made of the distribution of PHA-L labelled fibres and boutons in the mPFC. Labelled fibres were distributed in two tiers: predominantly within deep layer 1/layer 2 and also in layers 5/6. Fibre plexi in layers 2 and 5 were highly varicose. Electron microscopical examination of 120 labelled boutons in area 32 (60 in layer 2 and 60 in layer 5) indicated that 116 (97%) established asymmetrical synaptic contacts with dendritic spines and 4 (3%) were in synaptic contact with small dendritic shafts. No significant differences in target structures were found between layers 2 and 5. The results indicate that BLA input to mPFC in the rat predominantly innervates spine bearing dendrites in layers 2 and 5. This suggests that the neuronal operations of these processes are influenced by direct feedforward excitation from the BLA.     

A direct neuronal projection from the entopeduncular nucleus to the globus pallidus. A PHA-L anterograde tracing study in the rat

The efferent projections of the rat entopeduncular nucleus were examined by use of the anterogradely transported lectin Phaseolus vulgaris-leucoagglutinin (PHA-L). Injections of PHA-L into different parts of the entopeduncular nucleus resulted in a moderate number of labeled nerve fibers in the ipsilateral globus pallidus. The fibers displayed a heterogeneous morphology: some were of small caliber with few delicate varicosities, others were of medium caliber with several more bulbous nerve terminals. Restricted injections in the dorsal and ventral parts of the entopeduncular nucleus, respectively, showed that the dorsal part of the entopeduncular nucleus projects to the dorsal and rostral parts of the dorsal pallidum and the ventral part to the ventral and caudal parts.     

5-HT3-like receptors in the rat medial prefrontal cortex: an electrophysiological study.

In this study, we have identified and characterized 5-HT₃-like receptors in the rat medial prefrontal cortex (mPFc), an area with a moderate density of 5-HT₃ binding sites, using the techniques of single unit recording and microiontophoresis. The microiontophoresis of the 5-HT₃ receptor agonist 3-methylserotonin (2-Me-5HT), similar to the action of 5-HT), produced a current-dependent (10–80 nA) suppression of the firing rate of both spontaneously active and glutamate (GLU)-activated (quiescent) mPFc cells. Phenylbiguanide (PBG), another 5-HT₃ receptor agonist, suppressed the firing rate of mPFc cells but was less effective compared to 2-Me-5HT. The continuous iontophoresis (10–20 min) of 1 M magnesium chloride markedly attenuated the suppressant effect produced by electrical stimulation of the ascending 5-HT pathway, but did not alter 2-Me-5HT's action, suggesting that the action of 2-Me-5HT is a direct one. The suppressant action of 2-Me-5HT on mPFc cells was blocked by a number of structurally diverse and selective 5-HT₃ antagonists, with a rank order of effectiveness as follows: JCS 205930=(±)-zacopride>granisetron=ondansetron= LY 278584 >MDL72222. Furthermore, the intravenous administration of(±)-zacopride antagonized the action of 2-Me-5HT and PBG on mPFc cells. In contrast to the effects of the 5-HT₃ receptors antagonists, other receptor antagonists such as metergoline (5-HT_1A,1B,1C,2), (±)-pindolol (5-HT_1A,1B,β), SCH 23390 (5-HT_1C,2, D1), 1-sulpiride (D2) or SR 95103 (GABA_A) failed to block 2-Me-5HT's action. These results combined suggest that 2-Me-5HT's suppressive action on mPFc cells is mediated directly by 5-HT₃-like receptors.     

Forebrain connectivity of the prefrontal cortex in the marmoset monkey (Callithrix jacchus): an anterograde and retrograde tract-tracing study

The cortical and subcortical forebrain connections of the marmoset prefrontal cortex (PFC) were examined by injecting the retrograde tracer, choleratoxin, and the anterograde tracer, biotin dextran amine, into four sites within the PFC. Two of the sites, the lateral and orbital regions, had previously been shown to provide functionally dissociable contributions to distinct forms of behavioral flexibility, attentional set-shifting and discrimination reversal learning, respectively. The dysgranular and agranular regions lying on the orbital and medial surfaces of the frontal lobes were most closely connected with limbic structures including cingulate cortex, amygdala, parahippocampal cortex, subiculum, hippocampus, hypothalamus, medial caudate nucleus, and nucleus accumbens as well as the magnocellular division of the mediodorsal nucleus of the thalamus and midline thalamic nuclei, consistent with findings in the rhesus monkey. In contrast, the granular region on the dorsal surface closely resembled area 8Ad in macaques and had connections restricted to posterior parietal cortex primarily associated with visuospatial functions. However, it also had connections with limbic cortex, including retrosplenial and caudal cingulate cortex as well as auditory processing regions in the superior temporal cortex. The granular region on the lateral convexity had the most extensive connections. Based on its architectonics and functionality, it resembled areas 12/45 in macaques. It had connections with high-order visual processing regions in the inferotemporal cortex and posterior parietal cortex, higher-order auditory and polymodal processing regions in the superior temporal cortex. In addition it had extensive connections with limbic regions including the amygdala, parahippocampal cortex, cingulate, and retrosplenial cortex.     

The organisation of dendritic bundles in the prelimbic cortex (area 32) of the rat

Using an antibody against microtubule associated protein 2 (MAP-2; a specific marker for neuronal dendrites), this paper reports the structural organisation of pyramidal cell apical dendrites in the rat prelimbic (PL) cortex. In the coronal plane, MAP-2-immunoreactive apical dendrites of pyramidal neurons in layers 5, 3 and 2 were found bundled together as they ascended radially through the cortex. These bundles of dendrites dispersed in upper layer 2 to form apical dendritic tufts in layer 1. In tangential cross-section, the immunolabelled bundles were organised into a latticework of discrete clusters of differentially sized profiles. At the boundary between layers 3 and 5, clusters were composed of 26 ± 8 dendritic profiles (group mean value ± S.D., five animals), whereas clusters in layer 2 contained 55 ± 15 profiles. The number of clusters per unit surface area was not significantly different throughout layers 5, 3 and 2 (760 ± 75 per mm²) with the average centre-to-centre intercluster distance in these layers being 44.2 ± 4.9 μm. The data indicate that apical dendritic bundles are a feature of the radial organisation of PL cortex. These structural subunits may subserve specific integrative functions in the PL area of the rat medial prefrontal cortex.     

Efferent projections of the nucleus accumbens in the rat with special reference to subdivision of the nucleus: biotinylated dextran amine study

The nucleus accumbens (Acb) of the rat has been divided immunohistochemically into shell and core, and further, it was subdivided into several portions in relation to functional significance. In this report, the efferent projection of each subdivision of the Acb was examined using biotinylated dextran amine as an anterograde tracer. In rostral Acb, the dorsomedial shell mainly projected to the dorsomedial ventral pallidum (VP), lateral hypothalamus (LH) and substantia nigra pars compacta (SNc), while the ventromedial shell projected to the ventromedial VP, lateral preoptic area, LH and ventral tegmental area (VTA). The dorsal core of rostral Acb projected to the caudate putamen, dorsolateral VP, globus pallidus (GP), LH, and substantia nigra pars reticulata (SNr). In the middle to caudal Acb, the dorsomedial shell mainly projected to the dorsomedial VP, LH and VTA, the ventromedial shell projected to the ventromedial VP, substantia innominata, VTA, SNc and retrorubral area, and the ventrolateral shell projected to the ventrolateral VP and SNc. Furthermore, the ventromedial shell projected to the parabrachial nucleus (PB). The dorsomedial core projected to the dorsal VP, LH, SNc and SNr, and the ventral and lateral core sent axons to the dorsolateral VP, GP and SNc. From the point of view of projection patterns, shell and core are distinct throughout the rostro-caudal extent of the Acb. The ventrolateral shell at the caudal Acb was clearly differentiated. A direct projection from the ventromedial shell of the Acb to PB was also recognised.     

Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin

The purpose of the present investigation was to examine the topographical organization of efferent projections from the cytoarchitectonic divisions of the mPFC (the medial precentral, dorsal anterior cingulate and prelimbic cortices). We also sought to determine whether the efferents from different regions within the prelimbic division were organized topographically. Anterograde transport of Phaseolus vulgaris leucoagglutinin was used to examine the efferent projections from restricted injection sites within the mPFC. Major targets of the prelimbic area were found to include prefrontal, cingulate, and perirhinal cortical structures, the dorsomedial and ventral striatum, basal forebrain nuclei, basolateral amygdala, lateral hypothalamus, mediodorsal, midline and intralaminar thalamic nuclei, periaqueductal gray region, ventral midbrain tegmentum, laterodorsal tegmental nucleus, and raphe nuclei. Previously unreported projections of the prelimbic region were also observed, including efferents to the anterior olfactory nucleus, the piriform cortex, and the pedunculopontine tegmental-cuneiform region. A topographical organization governed the efferent projections from the prelimbic area, such that the position of terminal fields within target structures was determined by the rostrocaudal, dorsoventral, and mediolateral placement of the injection sites. Efferent projections from the medial precentral and dorsal anterior cingulate divisions (dorsomedial PFC) were organized in a similar topographical fashion and produced a pattern of anterograde labeling different from that seen with prelimbic injection sites. Target structures innervated primarily by the dorsomedial PFC included certain neocortical fields (the motor, somatosensory, and visual cortices), the dorsolateral striatum, superior colliculus, deep mesencephalic nucleus, and the pontine and medullary reticular formation. Previously unreported projections to the paraoculomotor central gray area and the mesencephalic trigeminal nucleus were observed following dorsomedial PFC injections. These results indicate that the efferent projections of the mPFC are topographically organized within and across the cytoarchitectonic divisions of the medial wall cortex. The significance of topographically organized and restricted projections of the rat mPFC is discussed in light of behavioral and physiological studies indicating functional heterogeneity of this region.     

Areal and synaptic interconnectivity of prelimbic (area 32), infralimbic (area 25) and insular cortices in the rat

This study investigated the interconnectivity of areas in the medial prefrontal and insular cortices in the rat. The areas studied were the prelimbic (PL, area 32) and infralimbic (IL, area 25) cortices and the dorsal anterior agranular insular (AId) and regions of posterior insular cortex (PI-comprising the agranular, dysgranular and granular fields). Following injections of the anterograde tracer biotinylated dextran amine (BDA) into layers 2-5 of each area, labelled axonal varicosities were found ipsilaterally in the other cortical areas. The most prominently labelled pathways were PL-->AId, AId-->PL, IL-->AId/PI, and PI-->IL. Qualitative and quantitative examinations of the laminar distribution of labelled axonal varicosities in the terminal fields indicated the existence of topographically organised 'feed-forward' (insular to PL/IL) and 'feed-back' (PL/IL to insular) pathways. The identity of the post-synaptic targets innervated by the PL/IL to AId pathways were investigated ultrastructurally. An analysis of 250 anterogradely labelled synaptic boutons (taken from layers 2/3) indicated that spine heads (presumed to originate from pyramidal cells) were the principal (88-93%) targets; all identified synaptic junctions were asymmetric. The results define an interconnected network of reciprocal pathways between cortical areas processing general and specific 'viscerosensory' information (AId and PI) and medial areas involved in cognitive (PL) and visceromotor (IL) functions. The data provide important aspects of the cortical circuitry underlying the integration of cognitive and emotional processing mechanisms, not only in rats, but also in primates.     

Efferent projections of the retrorubral nucleus to the substantia nigra and ventral tegmental area in cats as shown by anterograde tracing

The aim of the present study was to determine whether the retrorubral nucleus projects to the dopaminergic nuclei in the ventral midbrain of the cat. For this purpose, injections of biotinylated dextran-amine or Phaseolus vulgaris-leucoagglutinin were placed into the retrorubral nucleus under stereotaxic guidance. The tracers were visualized by means of (immuno) histochemical procedures. In addition, tyrosine hydroxylase immunohistochemistry was used to evaluate the location of the injection sites and the distribution of the anterogradely labeled fibers. Both tracers reveal the same topography of labeled fibers in the ventral mesencephalon. Labeled fibers with varicosities were found ipsilaterally in the substantia nigra pars compacta, the substantia nigra pars lateralis, the ventral tegmental area and, contralaterally, in the substantia nigra pars compacta, the ventral tegmental area, and the retrorubral nucleus. A considerable number of labeled axons with varicosities were observed to be wrapped around the dendrites and perikarya of tyrosine hydroxylase-positive neurons in these areas. The present results are discussed in view of the possible role of the A8 dopaminergic cell group in the coordination of A9 nigrostriatal and A10 mesolimbic systems, as well as in the progressive pathology seen in patients suffering from Parkinson's disease.     

Convergence of subthalamic and striatal efferents at pallidal level in primates: an anterograde double-labeling study with biocytin and PHA-L

Small injections of two highly sensitive anterograde tracers, Phaseolus vulgaris-leucoagglutinin (PHA-L) and biocytin, into the striatum and the subthalamic nucleus of squirrel monkeys (Saimiri sciureus) have revealed a high degree of convergence of striatal and subthalamic fibers upon single pallidal cells. Both afferent systems formed highly complex band-like patterns that were largely in register with one another. At single cell level, the somata of pallidal neurons were closely surrounded by subthalamic terminal varicosities, whereas the dendrites were entwined mostly by striatal fibers. Typically, a subthalamopallidal fiber coursed in a caudorostral direction and arborized according to a uniform pattern along its trajectory in the pallidum. Numerous thin and markedly varicose axon collaterals detached themselves at right angle from the main subthalamopallidal fiber. These highly branched collaterals were mostly oriented along the mediolateral plane and entwined rather loosely the dendrites but surrounded very closely the somata of pallidal neurons. In contrast, a striatopallidal fiber travelled in a rostrocaudal direction. Its initial segment made only en passant contacts with pallidal cell bodies, whereas its distal end closely entwined the dendrites of pallidal neurons, forming arrangements similar to 'woolly' type fibers. These results suggest that a single subthalamic fiber may influence a rather large collection of pallidal neurons in a similar fashion, compared to the striatal input which appears to exert a more specific control upon selected sets of the same pallidal neurons.     

Organization of projections from the medial agranular cortex to the superior colliculus in the rat: a study using anterograde and retrograde tracing methods

The organization of corticotectal projections from the medial agranular cortex (AGm), which has been considered to contain rat's frontal eye field, was examined using anterograde and retrograde tracing techniques. When biotinylated dextranamine (BDA) injections were made into the rostral part of the AGm, small numbers of BDA-labeled axons were found in the rostral two-thirds of the superior colliculus (SC) while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed mainly in the lateral part of the stratum griseum intermediale. On the other hand, after BDA injections into the caudal part of the AGm, moderate to dense plexuses of labeled axons were found in the rostral two-thirds of the SC while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed in the ventromedial and dorsolateral marginal zones of the stratum griseum intermediale as well as in the stratum griseum profundum. The corticotectal projections were largely uncrossed. After combined injections of BDA into the caudal part of the AGm on one side and cholera toxin B subunit (CTb) into the paramedian pontine reticular formation on the opposite side or into the interstitial nucleus of Cajal on the same side, the overlapping distributions of BDA-labeled axons and CTb-labeled neurons were found in the ventromedial marginal zone of the stratum griseum intermediale ipsilateral to the site of BDA injection. These results suggest that the caudal part of the AGm plays a more significant role in the oculomotor function than does the rostral part of the AGm.     

The corticocortical projections of the physiologically defined eye field in the rat medial frontal cortex

This study investigated in the rat the corticocortical projections of the frontal eye field (FEF), which is located within the medial frontal cortex. The experiments were carried out on Wistar rats. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in an FEF site within the medial frontal cortex where intracortical microstimulation elicited eye movements. In these cases, anterogradely labeled fibers and terminal-like elements were found in both hemispheres. The densest labeling was seen in the injected hemisphere, where labeled fibers prevailed in the visual cortex and their laminar distribution differed between the primary and secondary visual cortices. Dense labeled fibers were also seen in the frontal and retrosplenial cortex, whereas a columnar arrangement of terminal-like elements was detected in a restricted part of area 1 of the somatosensory cortex. Contralaterally to the injection site, labeled fibers were distributed mainly in the homotopic region. In two animals, the tracer was injected in a site at the FEF border whose stimulation evoked eye and whisker movements. In these animals, a different distribution of labeling was observed with respect to the other rats in which the tracer was deposited within the FEF, and anterograde labeling was observed in areas 1 and 2 of the parietal cortex of both hemispheres; in addition, no labeling was observed in these cases in the primary visual cortex. These findings suggest that cortical sites confined within the rat FEF are implicated in the control of orienting and exploring behaviors in addition to the control of eye movement.     

Light microscopic evidence of striatal input to intrapallidal neurons of cholinergic cell group Ch4 in the rat: a study employing the anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L)

Injections of the anterograde tracerPhaseolus vulgaris leucoagglutinin (PHA-L) were placed in various striatal loci in the rat. Within the globus pallidus, PHA-L-filled striatofugal axons were seen to approach cholinergic neurons, identified with either acetylcholinesterase histochemistry or choline acetyltransferase immunohistochemistry, and, apparently, to contact the surface of such cells with axonal varicosities. Since these varicosities are thought to mark the sites of synaptic terminals, such juxtapositions provide strong light-microscopic evidence that intrapallidal cholinergic neurons in the rat receive a direct innervation from the striatum and are integrated into the circuitry of the basal ganglia.     

Projection from the prefrontal cortex to histaminergic cell groups in the posterior hypothalamic region of the rat. Anterograde tracing withPhaseolus vulgaris leucoagglutinin combined with immunocytochemistry of histidine decar☐ylase

We investigated the projection from the infralimbic division of the prefrontal cortex (area 25) to histaminergic neurons in the posterior hypothalamic area.Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in the prefrontal cortex of rats. Frozen brain sections were subjected to combined PHA-L and histidine decar☐ylase (HDC)-peroxidase immunocytochemistry, using nickel-enhanced diaminobenzidine (blue reaction product) to visualize the transported PHA-L, and diaminobenzidine (brown reaction product) to visualize simultaneously the HDC-containing neurons. PHA-L-labeled fibers could be seen coursing in the capsula interna, leaving the telencephalon via the anterior thalamic radiation and the medial forebrain bundle. In the lateral and posterior hypothalamic areas, PHA-L-labeled fibers leave the medial forebrain bundle and traverse the nuclei containing HDC-immunoreactive neurons. Varicosities on the PHA-L-labeled fibers, the majority of which occur en passant, could be observed in close association with the HDC-immunoreactive neurons. The results suggest that the hypothalamic histaminergic neurons receive afferent synaptic input from neurons of the infralimbic division of the prefrontal cortex.