The primate mediodorsal (MD) nucleus and its projection to the frontal lobe

The frontal lobe projections of the mediodorsal (MD) nucleus of the thalamus were examined in rhesus monkey by transport of retrograde markers injected into one of nine cytoarchitectonic regions (Walker's areas 6, 8A, 9, 10, 11, 12, 13, 46, and Brodmann's area 4) located in the rostral third of the cerebrum. Each area of prefrontal, premotor, or motor cortex injected was found to receive a topographically unique thalamic input from clusters of cells in specific subdivisions within MD. All of the prefrontal areas examined also receive topographically organized inputs from other thalamic nuclei including, most prominently, the ventral anterior (VA) and medial pulvinar nuclei. Conversely, and in agreement with previous findings, MD projects to areas of the frontal lobe beyond the traditional borders of prefrontal cortex, such as the anterior cingulate and supplementary motor cortex. The topography of thalamocortical neurons revealed in coronal sections through VA, MD, and pulvinar is circumferential. In the medial part of MD, for example, thalamocortical neurons shift from a dorsal to a ventral position for cortical targets lying medial to lateral along the ventral surface of the lobe; neurons in the lateral MD move from a ventral to a dorsal position, for cortical areas situated lateral to medial on the convexity of the hemisphere. The aggregate evidence for topographic specificity is supported further by experiments in which different fluorescent dyes were placed in multiple areas of the frontal lobe in each of three cases. The results show that very few, if any, thalamic neurons project to more than one area of cortex. The widespread cortical targets of MD neurons together with evidence for multiple thalamic inputs to prefrontal areas support a revision of the classical hodological definition of prefrontal cortex as the exclusive cortical recipient of MD projections. Rather, the prefrontal cortex is defined by multiple specific relationships with the thalamus.     

Cortical projections to the lower brain stem and spinal cord in the tree shrew (Tupaia glis)

A study was made of corticofugal projections to the lower brain stem and spinal cord in the tree shrew (Tupaia glis). Degeneration resulting from selective ablations of the motor, sensory and frontal cortex in ten animals was studied by the Nauta technique. Following ablations of motor and sensory cortex degeneration was found bilaterally: (1) throughout the rostrocaudal extent of the lateral reticular formation, (2) in all trigeminal sensory nuclei and, (3) in the dorsal column nuclei (contralateral predominance). All three cortical areas projected fibers to the ipsilateral pontine nuclei and bilaterally to the medial reticular formation (ipsilateral predominance). Fibers from the motor cortex were distributed throughout the medial reticular formation; fibers from sensory and frontal cortex were distributed to selective regions of the medial reticular formation. The majority of corticospinal fibers decussated and descended to lower cervical (frontal fibers) and lower thoracic (motor and sensory fibers) levels. The small uncrossed component descended in the ipsilateral dorsal funiculus only throughout cervical segments. Corticospinal degeneration terminated primarily in the internal basilar region (medial half of lamina VI), medial aspect of the neck (lamina V) and, to a lesser extent, in the head (laminae III and IV) of the dorsal horn. Relatively few fibers projected to the zona intermedia (lamina VII) and no terminations were present in the motor nuclei (lamina IX) of the spinal nerves.     

Corticocortical and thalamocortical projections to layer I of the frontal neocortex in rats

Layer I of the neocortex is a dense synaptic zone consisting of horizontal corticocortical and widespread layer VII projections, in addition to thalamic inputs. In order to determine the origin and extent of corticocortical and thalamocortical projections to layer I of the frontal/premotor area M2 of the rat neocortex, we have used fluorescent anatomical tracing methods to determine the precise sources of cortical and thalamic input to the rostral and caudal aspects of layer I of M2. Retrograde tracer diamidino yellow (DY), applied directly to the pial surface on rostral or caudal areas of rat M2 (RM2 and CM2, respectively) labeled cells ipsilaterally throughout layers II/III, V, and VII of the adjacent primary motor area and the parietal areas (SI and SII). In addition, retrograde transport labeled contralateral CM2 or RM2 in layers II/III and V at sites homotopic to either CM2 or RM2 application sites. Contralateral layer VII was retrogradely labeled by the application to layer I of CM2, but not by the RM2 application. Retrograde DY transport from layer I of RM2 or CM2 of was seen in the ventral medial (VM), ventral lateral (VL), and posterior (Po) thalamic nuclei. However layer I transport from CM2 additionally labeled the thalamic central medial (CM) nucleus, while the RM2 labeled the mediodorsal (MD) thalamic nucleus. Upon determination that thalamic nuclei VM and VL were of primary interest in this study, due to their dense retrograde labeling, injections of anterograde tracer rhodamine dextranamine (RDA) into VM or VL were performed in order to study the projection patterns of these nuclei to layer I of the frontal cortex. RDA injections into VM labeled fibers extending through layer I of both RM2 and CM2 and throughout the cingulate cortex. Injections of RDA into VL consistently labeled dense fibers in layer I of both CM2 and RM2, although labeling was sharply decreased anterior to CM2. This study adds to a growing body of evidence that projections to layer I from all sources of cortical input make a significant contribution to integration throughout the neocortex.     

The afferent and efferent connections of the ventromedial thalamic nucleus in the rat

The afferent and efferent connections of the ventromedial (VM) nucleus of the thalamus in the rat were studied by experiments using the methods of retrograde cell marking by horseradish peroxidase (HRP) and anterograde fiber tracing by autoradiography. Tritiated amino acids deposited microelectrophoretically into VM label a cortical projection that is distributed to a sharply defined superficial portion of layer I of almost the entire extent of the ipsilateral neocortex. The labeling is most dense at frontal cortical levels, where fibers radiate through the deeper layers to terminate in the outer one-quarter of layer I throughout all neocortex rostral to the genu of the corpus callosum. A lesser number of labeled fibers extends caudally in a supracallosal location to innervate parieto-occipital cortical areas. Labeled collaterals ascend through the cortical layers to reach layer I, where grains in the superficial portion are found in a gradually decreasing rostrocaudal gradient of density that reaches the caudal pole of the hemisphere. Coronal sections at most levels contain a band of labeling in layer I that extends uninterrupted from the callosal sulcus at the midline to the banks of the rhinal sulcus laterally. Caudal retrosplenial and ventral temporal areas appear to be the only sectors of neocortex spared by the ubiquitous projection. Evidence for additional terminal distribution in deeper layers is found only in the dorsal and lateral sectors of the cortex rostral to the genu where sparsely labeled bands appear in layers III and V. The nearly exclusive distribution of VM's cortical afferents to layer I is compared and contrasted with multilaminar distributions of other “unspecific” cortical afferent fibers. HRP injected into VM labels neurons in a variety of structures at levels ranging from the frontal cortex to caudal medulla. Cell labelling in the globus pallidus, deep layers of the superior colliculus, cerebellar nuclei and the substantia nigra, pars reticulata suggest that VM is a point of convergence for several components of the extrapyramidal motor system. The nigrothalamic projection is topographic: medial and lateral districts of the pars reticulata are connected to medial and lateral districts of VM, respectively. A dorsal-ventral association may also obtain. Cell labeling in the prefrontal cortex, the cortex along the rhinal sulcus, the lateral habenular nucleus, tegmental and medullary reticular formations, and parabrachial nuclei indicates that VM also receives projections from more heterogeneous sources.     

Corticothalamic connections of paralimbic regions in the rhesus monkey

This study addressed the issue of whether paralimbic regions of the cerebral cortex share common thalamic projections. The corticothalamic connections of the paralimbic regions of the orbital frontal, medial prefrontal, cingulate, parahippocampal, and temporal polar cortices were studied with the autoradiographic method in the rhesus monkey. The results revealed that the orbital frontal, medial prefrontal, and temporal polar proisocortices have substantial projections to both the dorsomedial and medial pulvinar nuclei, whereas the anterior cingulate proisocortex (area 24) projects exclusively to the dorsomedial nucleus. These proisocortical areas also have thalamic connections with the intralaminar and midline nuclei. The cortical areas between the proisocortical regions on the one hand and the isocortical areas on the other, that is, the posterior cingulate region (area 23) and the posterior parahippocampal gyrus (areas TF and TH), project predominantly to the dorsal portion of the medial pulvinar nucleus, the anterior nuclear group (AV, AM), and the lateral dorsal (LD) nucleus. Additionally, the posterior cingulate and medial parahippocampal gyri (area TH) have projections to the lateral posterior (LP) nucleus. Thus, it appears that the proisocortical areas, which are characterized by a predominance of infragranular layers and an absence of layer IV, have common thalamic relationships. Likewise, the intermediate paralimbic areas between the proisocortex and isocortical regions, which also have a predominance of infragranular layers but in addition have evidence of a fourth layer, project to the medial pulvinar and to the so-called limbic nuclei, AV, AM, LD, as well as a modality-specific nucleus, LP.     

Prosencephalic afferents to the mediodorsal thalamic nucleus

The afferent projections from the prosencephalon to the mediodorsal thalamic nucleus (MD) were studied in the cat by use of the method of retrograde transport of horseradish peroxidase (HRP). Cortical and subcortical prosencephalic structures project bilaterally to the MD. The cortical afferents originate mainly in the ipsilateral prefrontal cortex. The premotor, prelimbic, anterior limbic, and insular agranular cortical areas are also origins of consistent projections to the MD. The motor cortex, insular granular area, and some other cortical association areas may be the source of cortical connections to the MD. The subcortical projections originate principally in the ipsilateral rostral part of the reticular thalamic nucleus and the rostral lateral hypothalamic area. Other parts of the hypothalamus, the most caudal parts of the thalamic reticular nucleus, the basal prosencephalic structures, the zona incerta, the claustrum, and the entopeduncular and subthalamic nuclei are also sources of projections to the MD. Distinct, but somewhat overlapping areas of the prosencephalon project to the three vertical subdivisions of MD (medial, intermediate, and lateral). The medial band of the MD receives a small number of prosencephalic projections; these arise mainly in the caudal and ventral parts of the prefrontal cortex. Cortical projections also arise in the infralimbic area, while subcortical projections originate in the medial part of the rostral reticular thalamic nucleus and lateral hypothalamic area. The intermediate band of the MD receives the largest number of fibers from the prosencephalon. These arise principally in the intermediate and dorsal part of the lateral and medial surface of the prefrontal cortex, the premotor cortex, and the prelimbic and agranular insular areas. Projections also originate in basal prosencephalic formations (preoptic area, Broca's diagonal band, substantia innominata, and olfactory tubercle), rostral reticular thalamic nucleus, and lateral hypothalamic area. A large number of prosencephalic structures also project to the lateral band of the MD. These are mainly the most dorsal and caudal parts of the lateral and medial surface of the prefrontal cortex, the premotor and motor cortices, and the prelimbic, anterior limbic, and insular areas. Projections arise also in the lateral rostral and caudal parts of the reticular thalamic nucleus, the zona incerta, the lateral and dorsal hypothalamic areas, the claustrum, and the entopeduncular nucleus. These and previous results demonstrate a gradation in the afferent connections to the three subdivisions of the MD. Brain structures related to the olfactory sensory modality and with allocortical formations of the limbic system project principally to the medial band of the MD. The intermediate band of the MD receives subcortical and cortical projections from structures mainly related to the limbic system and cortical regions related to sensory association cortices. The lateral band of the MD receives projections mainly originating in structures related to complex sensory associative processes and to the motor system (especially from brainstem and cortical structures implicated in the regulation of eye movements).     

Adult rat motor cortex connections to thalamus following neonatal and juvenile frontal cortical lesions: WGA-HRP and amino acid studies

Frontal cortex was removed in 1- and 30-day-old rats. When both groups reached 90 days of age, the forelimb motor/sensory cortex in the unlesioned hemisphere was injected with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or tritiated leucine. Thalamic neurons were retrogradely labeled only ipsilateral to the WGA-HRP injection site in both neonatally and juvenile-lesioned subjects. Ventrolateral (VL), ventromedial (VM), centromedial (CM), centrolateral (CL), parafascicular (PF), posteromedial (POm), and posterior (PO) thalamic nuclei were labeled. This and the demonstration of only ipsilateral thalamocortical connections at birth helped explain the marked thalamic atrophy which developed ipsilateral to neonatal frontal cortex lesions. Death of thalamic neurons after neonatal removal of their normal cortical target could be due to their failure to sprout into the opposite cortex because that cortex was already innervated by the opposite thalamus at birth. Leucine motor/sensory cortex injections in both neonatally and juvenile-lesioned subjects labeled the ipsilateral VL, VM, CM, CL, PF, POm, and PO thalamic nuclei; contralateral CM, CL, and PF thalamic nuclei; ipsilateral medial, ventral, and lateral pontine nuclei; and parts of the contralateral pontine nuclei. The ipsilateral connections were always more robust than the contralateral connections. The contralateral corticothalamic and corticopontine projections, however, were much more numerous and widespread in neonatally compared to juvenile-lesioned subjects. The greater sparing of some motor functions said to occur in neonatal compared to adult motor cortex-lesioned subjects could be due to the plasticity of corticothalamic, corticopontine, and other corticofugal pathways, but not to the plasticity of thalamocortical pathways.     

Thalamic connections with limbic cortex. I. Thalamocortical projections

The thalamocortical projections to limbic cortex in the cat have been studied with retrograde and anterograde axonal transport techniques. Five limbic cortical areas were identified on the basis of cytoarchitecture. The five areas are the anterior limbic area, the cingular area, the dorsal and ventral retrosplenial areas, and the presubiculum. Each of these cortical areas received small injections of horseradish peroxidase, and the afferent thalamic nuclei were identified by retrograde labelling of cells. The cortical projection of each of the anterior thalamic nuclei and the lateral dorsal nucleus was determined autoradiographically. Each of the anterior thalamic nuclei and the lateral dorsal nucleus projects to limbic cortex by two pathways. One group of fibers leaves the rostral thalamus by the fornix, pierces the corpus callosum, and joins the cingulate fasciculus to reach limbic cortex. The other group travels through the lateral thalamic peduncle and internal capsule. The anterior ventral nucleus projects primarily to the dorsal retroslenial area, particularly to layer I, the deep portion of layer II, and superficial portion of layer III. Sparse projections also exist to the ventral retrosplenial area, the cingular area, and the presubiculum. Very sparse projections to the anterior limbic area are seen. The anterior dorsal nucleus projects primarily to the ventral retrosplenial area, particularly layers I, the deep portion of layer II, and superficial layer III. Sparse projections exist to the dorsal retrosplenial area and presubiculum, but apparently no projections exist to the cingular or anterior limbic area. The anterior medial nucleus projects primarily to layers I and superficial III of the ventral retrosplenial area. Sparse projections exist to each of the other limbic cortical areas. The lateral dorsal nucleus projects extensively onto limbic cortex. Prominent projections occur to layer I, the external granular layer and lamina dessicans of the presubiculum, layers I and III-IV of the dorsal retrosplenial area, and layers I, III, and IV of the cingular area. Sparse projections occur to the ventral retrosplenial area and the anterior limbic areas. Thalamocortical projections also originate in the midline and intralaminar nuclei including the central medial reuniens, rhomboid, paracentral, central lateral, and central dorsal nuclei. These data indicate that the anterior thalamic nuclei project upon limbic cortex in a complex manner. Further, the projections to limbic cortex from the anterior nuclei overlap with projections from the lateral dorsal nucleus. This overlap of thalamic projections onto limbic cortex suggests a convergence of information from nonprimary sensory systems with information from the classical limbic system.     

Synaptic organization and input-specific short-term plasticity in anterior cingulate cortical neurons with intact thalamic inputs

The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long-distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT-ACC neuronal pathway plays an integral role in information transmission. Biocytin-labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. Eighty-seven cells downstream of the thalamic projections in 49 slices were recorded intracellularly. Intracellular recordings in the ACC showed that thalamocingulate transmission involves both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Thalamus-evoked responses recorded extracellularly in the ACC were activated and progressed along a deep-superficial-deep trajectory loop across the ACC layers. We observed enhanced paired-pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input-specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT-evoked ACC synaptic transmission to short-term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.     

Afferent connections of the thalamic intralaminar nuclei in the cat

Afferents to the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) from cortical and subcortical sites were studied in the cat. We utilized stereotaxically guided injections of HRP into the CL and PC nuclei and tritiated leucine injections into various visual, parietal and limbic areas of cortex to demonstrate these connections. In studying the relatively weak visual cortical projections to the ILN, we demonstrated projections from areas 19, 20a, 21a, 21b, AMLS, PMLS and PLLS. However, our HRP injections into the ILN often revealed only a few labeled cells in any of the above areas; therefore conclusions regarding the absence of projections to ILN from remaining visual cortical areas should be made cautiously. The ILN receive heavier projections from the frontal eye fields, cingulate cortex, splenial cortex, insular cortex, somatosensory areas SI and SII, auditory areas SF, AII, and Ep, and parietal areas 5 and 7. The most robust projections appear to be from from frontal eye fields, cingulate and parietal areas. No topography was apparent in the projections to the ILN. All cortical projections originate ipsilaterally from layers V and VI. Heavy subcortical projections to the ILN originate in the pretectum, superior colliculus, reticular formation, and periaqueductal grey. Fewer afferents arise from several other brainstem and thalamic nuclei.     

Efferent projections of the thalamic intralaminar nuclei in the cat

Efferent projections of the central lateral (CL), paracentral (PC) and central medial (CE) intralaminar nuclei (ILN) to cortical and subcortical sites were studied in the cat. The combined methods of electrophysiologically guided cortical injections of tritiated leucine and stereotaxic injections of horseradish peroxidase (HRP) into the CL and PC nuclei were utilized. Additionally, fluorescent double-labeling techniques demonstrated patterns of intralaminar axon collateralization. We found that the ILN project ipsilaterally to all visual cortical areas except area 17. Projections to visual cortex are not arranged topographically or retinotopically. The ILN also project to the frontal eye fields (areas 6 and 8), anterior cingulate gyrus, suprasylvian fringe of the auditory cortex, insular cortex, parietal areas 5 and 7, caudate nucleus and claustrum. We noted especially heavy projections to the frontal eye fields and parietal areas 5 and 7. Fibers from the ILN terminate in cortical layers I and VI, and at the layer III-IV border. The demonstration of collateralization of ILN axons to two separate cortical areas implies that the same neuronal message may pass from the ILN to multiple cortical areas. It is concluded that the ILN may mediate a general cortical activation and may play a role in attention to visual, auditory and somatosensory (especially nociceptive) stimuli.     

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.     

Quantitative analyses of thalamic and cortical origins of neurons projecting to the rostral and caudal forelimb motor areas in the cerebral cortex of rats

On the basis of studies using intracortical microstimulation, the existence of rostrocaudally separate two forelimb representation areas has been inferred in the motor cortex of rats. They are termed caudal and rostral forelimb areas (CFA and RFA). In this study, it was confirmed first that RFA and CFA are located in cytoarchitectonically distinct areas (medial and lateral parts of agranular cortex (AGm and AGl), respectively). In the second part of this study, the distribution of thalamic and cortical neurons projecting to RFA and CFA was quantitatively compared by injections of small and relatively constant amounts of retrograde fluorescent dyes (diamidino yellow and fast blue) into these areas. It was observed that (1) main inputs to RFA originated from AGl, namely CFA (2) CFA received dominant inputs from AGm including RFA and caudally adjacent granular cortex and (3) wider cortical areas and larger number of neurons projected to CFA than to RFA. As for the thalamocortical projections, both RFA and CFA received inputs from various thalamic nuclei, such as VL, VM, Po, PC, PF, CL, but cells projecting to RFA and CFA were differentially located in each nucleus. It was found that labeled cell number and/or density in VM, PC, CL, CM and MD after RFA injections were significantly larger than those after CFA injections. On the other hand, labeled cell number and/or density in VPL and VL were significantly higher after CFA injections than after RFA injections. In comparison with findings in primates, the results suggest that the cortical motor areas of rats may be specialized for different aspects of motor control.     

Numerical data on neocortical neurons in adult rat, with special reference to the GABA population

The disector method was used to estimate the numerical density of neurons (number per unit volume) and their actual number per column (number under a given area of pial surface), in the occipital (monocular segment of the primary visual area, Oc1M), the parietal (somatosensory barrelfield area, Par1) and the frontal cortex (primary motor area, Fr1) of adult rat. Values were first obtained for all neurons in each layer, and then for GABA neurons as identified with postembedding immunocytochemistry on semithin sections. The numerical density of neurons in the frontal cortex (34,000/mm³) was significantly lower than in the two other neocortical areas (occipital: 52,000; parietal: 48,000/mm³). The GABA population showed a similar difference and consequently represented an equivalent proportion of total (15%) in the three cortical areas. Across layers, there was an alternate distribution of low and high density of neurons from layers II–III to VI in the three cortical areas, with the highest density in layer IV of the two sensory areas. The laminar changes in density of the GABA neurons were not as pronounced as those of the overall population. Consequently, the layers with the highest overall neuronal densities tended to have a lower proportion of GABA neurons and vice versa. There were more neurons under 1 mm² of surface in the parietal (90,000) than the occipital or the frontal cortex (71,000), which was also true of the GABA neurons. The greater number of neurons per column in the parietal cortex was mostly imputable to layer IV, the main recipient of thalamic axons. Comparing these values from the rat with those previously obtained in cat and monkey, it seemed that the number of neurons per cortical column was the highest in the sensory area preferentially used by each species.     

Distribution of association fibers impinging upon the middle suprasylvian sulcus area (MSs area) in the cat (author's transl)

Following lesions of various cortical areas of altogether 13 adult cats, the distribution of degenerating fibers in the cortical area surrounding the middle suprasylvian sulcus (MSs area) has been studied with the method of Fink and Heimer. Association fibers from the visual cortex mostly end in the vicinity of fundus of the medial wall of the MSs area and a fair number of fibers do in the fundus area of the posterior portion of its lateral wall. Most of the fibers terminate in layers III-V. Fibers from the auditory cortex terminante in the lip of the lateral wall, while few fibers end in the fundus and the medial wall. The fibers from the somatosensory cortex chiefly end in the vicinity of the fundus terminate in layers III-V. The "association cortex" sends a good amount of fibers to the lip region and the upper area of the media wall and lesser amount to the posterior part of the lateral wall of the MSs. The fibers terminant in layer III. From the present and the previous findings, it has become evident that inputs of different kinds of sensory modalities converge upon th elayers III-IV of the MSs area from the various cortical functional areas, and that the MSs area also sends fibers back to the sensory cortical areas. In addition, it has reciprocal connections with some thalamic nuclear groups, e.g., the "pulvinar posterior" system. Based upon the findings of neuronal connections, it can be suggested that the MSs area may play an important role with regard to the "integration of sensory inputs" in the cat cerebral cortex.     

Opiate receptor localization in rat cerebral cortex

The differential distributions of [3H]naloxone-labeled and [3H]D-Ala-D-Leu-enkephalin-labeled opiate receptors in rat cerebral cortex were localized autoradiographically and quantified by grain counting and computerized densitometry. In addition, receptor distributions were compared to terminal patterns of thalamocortical projections labeled by axoplasmic transport of [3H]amino acids. Opiate receptors labeled with [3H]naloxone in a mu ligand selectivity pattern show striking laminar heterogeneity and are densest in limbic cortical areas, intermediate in the motor cortex, and fewest in the primary sensory areas. By contrast, opiate receptors labeled with [3H]D-Ala2-D-Leu5-enkephalin in a delta ligand selectivity pattern are much more homogeneously distributed across both regions and laminae within regions. Mu receptors in most cortical areas have density peaks in layers I and VI and each peak shows a density gradient that is sloped within the layer so that the highest densities are at the most superficial and the deepest portions of cortex. In addition, there is an intermediate peak whose laminar position varies depending on the area in which it is found. In rostral agranular cortex, including limbic and motor areas, the [3H]naloxone binding peaks are in layers I, III, and VI. In primary somatosensory cortex, the intermediate peak is in layer Va and in most of remaining homotypical cortex it is in layer IV. Some areas have only bilaminar labeling, in superficial and deep layers; these include portions of the sulcal and retrosplenial cortices. Piriform and entorhinal cortices have dense [3H]naloxone binding only in the deepest layer and show a descending gradient of density toward the superficial layer. The positions of the mu receptor peaks were compared with termination patterns of projections originating in the thalamus. Close correspondence was found between receptor binding in the prelimbic, primary somatosensory, and entorhinal areas and projection terminations arising from the thalamic mediodorsal, posterior, and central medial nuclei, respectively. Although regional variations in [3H]D-Ala2-D-Leu5-enkephalin-labeled receptor density are uncommon, a gradual decrease in the number of sites along the dorsomedial wall of the cortex from anterior cingulate to caudal retrosplenial limbic cortex can be observed. Laminar variations in binding density are small as well; higher concentrations of the peptide binding sites are usually found in the deep cortical layers. These findings emphasize aspects of opiate receptor architecture which may be relevant to identifying cortical "opiatergic" neurocircuitry and raise the possibility of opiate modulation of thalamocortical transmission.     

Cholinergic and monoaminergic innervation of the cat's thalamus: comparison of the lateral geniculate nucleus with other principal sensory nuclei

The cholinergic and monoaminergic innervation of the lateral geniculate nucleus (GL) and other thalamic nuclei in the cat was examined by using immunocytochemical and tract-tracing techniques. Cholinergic fibers, identified with an antibody to choline acetyltransferase (ChAT), are present in all layers of the GL. They are fine in caliber and exhibit numerous swellings along their lengths. The A layers, the magnocellular C layer, and the medial interlaminar nucleus are rich in cholinergic fibers that give rise to prominent clusters of boutons, while the parvicellular C layers contain fewer fibers that are more uniformly distributed. The interlaminar zones are largely devoid of ChAT-immunoreactive fibers. Double-label experiments show that cholinergic projections to the GL originate from two sources, the pedunculopontine reticular formation (PPT) and the parabigeminal nucleus (Pbg). The PPT contributes cholinergic fibers to all layers, while Pbg projections are limited to the parvicellular C layers. The lateral geniculate nucleus has a much greater density of cholinergic fibers than the other principal sensory nuclei: the density of fibers in the A layers is more than three times greater than that in the ventral posterior nucleus (VP) or the ventral division of the medial geniculate nucleus (GMv). In contrast, serotonin (5-HT)-immunoreactive fibers are distributed with equal density across the principal thalamic nuclei, while tyrosine hydroxylase (TH)-immunoreactive fibers (presumed to contain norepinephrine) are noticeably less dense in the GL than in the others. Monoaminergic fibers also differ from cholinergic fibers in their laminar distribution within the GL: both TH- and 5HT-immunoreactive fibers are distributed evenly across the layers and interlaminar zones and are slightly more abundant in the parvicellular C layers than in the other layers. Other thalamic nuclei rich in cholinergic fibers include the pulvinar nucleus, the ventral lateral geniculate nucleus, the intermediate nucleus of the lateral group, the lateral medial and suprageniculate nuclei (Graybiel and Berson: Neuroscience 5:1175-1238, '80), and the paracentral and central-lateral components of the intralaminar nuclei. This pattern matches the distribution of projections from the PPT and is similar, but not identical, to the pattern of acetylcholinesterase staining. The fact that most of the nuclei rich in cholinergic fibers have been implicated in visual sensory or visual motor functions suggests that cholinergic projections from the reticular formation play an especially important role in visually guided behavior.     

PHA-L analysis of projections from the supramammillary nucleus in the rat.

The projections of the supramammillary nucleus (SUM) were examined in the rat by the anterograde anatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The majority of labeled fibers from SUM ascended through the forebrain within the medial forebrain bundle. SUM fibers were found to terminate heavily in the hippocampal formation, specifically within the granule cell layer and immediately adjoining molecular layer of the dentate gyrus. In addition, SUM fibers were shown to distribute densely to several structures with strong connections with the hippocampus, namely, the nucleus reunions of the thalamus, the medial and lateral septum, the entorhinal cortex, and the endopiriform nucleus. SUM fibers were also shown to project significantly to several additional subcortical and cortical sites. The subcortical sites were the dorsal raphe nucleus, the midbrain central gray, the fields of Forel/zona incerta, the dorsomedial hypothalamic area, midline/intralaminar nuclei of the thalamus (posterior paraventricular, rhomboid, central medial, intermediodorsal, and mediodorsal), the medial and lateral preoptic areas, the bed nucleus of the stria terminalis, the substantia innominata, the vertical limb of the diagonal band nucleus, and the claustrum. The cortical sites were the occipital, temporal, parietal, and frontal cortices. Some notable differences were observed in projections from the lateral as compared to the medial SUM. For example, fibers originating from the lateral SUM distributed heavily to the hippocampal formation and parts of the cortex, whereas those from the medial SUM projected sparsely to these two regions. The SUM projections to the hippocampal formation and associated structures may serve as the substrate for a SUM involvement in the generation of the theta rhythm of the hippocampus and the gating of information flow through the hippocampal formation.     

Differential projection patterns of superior and inferior collicular neurons onto posterior paralaminar nuclei of the thalamus surrounding the medial geniculate body in the rat

The thalamic nuclei at the medial border of the medial geniculate body (i.e. the suprageniculate nucleus, the medial division of the medial geniculate nucleus, the posterior intralaminar nucleus and the peripeduncular nucleus) which relay sensory information to the amygdala are thought to receive convergent input from multiple sites. In order to delineate the organization of these multimodal thalamic nuclei, the locations of superior and inferior collicular neurons projecting to these nuclei were studied by means of retrograde transport methods. Small injections of the tracer Miniruby were made into single paralaminar thalamic nuclei. Injections of Miniruby into the suprageniculate nucleus labelled predominantly neurons in the stratum opticum of the superior colliculus, whereas injections into the medial division of the medial geniculate body, the posterior intralaminar nucleus and the peripeduncular nucleus labelled predominantly neurons in the deep layers of the superior colliculus. These injections also labelled neurons in the inferior colliculus. The majority of retrogradely labelled neurons were found in the external nucleus of the inferior colliculus and here predominantly in layer 2. Injections focused onto the medial division of the medial geniculate body additionally labelled magnocellular neurons in layer 3 of the external nucleus and a few neurons in the central nucleus. More ventrally located injections, focused onto the posterior intralaminar and peripeduncular nucleus, almost exclusively labelled neurons in layer 1 of the external nucleus and the dorsal part of the dorsal nucleus. After injections into the suprageniculate nucleus, only neurons in layer 2 were found. Neurons in the central nucleus of the inferior colliculus were only found after injections that involved the medial division of the medial geniculate body. The present results suggest that, despite a considerable degree of convergence in this thalamic region, each of these thalamic nuclei receives a unique pattern of projections from the superior and inferior colliculi. It appears that the thalamic nuclei may be concerned mainly, but not exclusively, with a single sensory modality, and give rise to parallel multimodal and unimodal pathways to the amygdala.     

The topographic organization of associational fibers of the olfactory system in the rat, including centrifugal fibers to the olfactory bulb

This study analyzed the topographic organization of the associational fibers within the olfactory cortex of the rat, by using the autoradiographic method. Small injections of 3H-leucine were placed in all of the subdivisions of the olfactory cortex, to label selectively the fibers arising in each area. Intracortical fibers were identified from all of the olfactory cortical areas except the olfactory tubercle and were classified into two major systems (the layer Ib system and the layer II-deep Ib system) on the basis of their laminar pattern of termination (see Luskin and Price, '83). The layer Ib fiber system arises in the anterior olfactory nucleus, piriform cortex, and lateral entorhinal area, and is broadly organized in relation to the lateral olfactory tract. Cortical areas deep to or near the lateral olfactory tract are preferentially interconnected with areas near the tract, while parts of the cortex lateral and caudal to the lateral olfactory tract are most heavily interconnected with areas lateral, caudal, and medial to the tract. Commissural projections from the anterior olfactory nucleus and the anterior piriform cortex match some (but not all) components of the ipsilateral layer Ib fiber system. The layer II-deep Ib fiber system arises in three small areas--the ventral tenia tecta, the dorsal peduncular cortex, and the periamygdaloid cortex. The fibers from the ventral tenia tecta terminate in layer II of the anterior olfactory nucleus and are topographically organized. The fibers from the dorsal peduncular cortex and the periamygdaloid cortex are more widely distributed, especially in the lateral and caudal parts of the cortex. Two other intracortical projections do not fit into either of these fiber systems. The nucleus of the lateral olfactory tract projects bilaterally to the islands of Calleja and the medial edge of the anterior piriform cortex. The anterior cortical nucleus projects to many parts of the olfactory cortex, but the fibers end in both superficial and deep parts of layer I (layer Ia and Ib). There are projections from several of the olfactory cortical areas to the cortical areas surrounding the olfactory cortex. Virtually all of the olfactory areas also project to the ventral and dorsal endopiriform nuclei deep to the piriform cortex and/or to the polymorph zone deep to the olfactory tubercle. In addition, projections have been demonstrated to the deep amygdaloid nuclei, especially from the more ventromedial and caudal parts of the olfactory cortex.