Single-axon tracing and three-dimensional reconstruction of centre median-parafascicular thalamic neurons in primates

The axonal projections from the centre median (CM)/parafascicular (Pf) thalamic complex in squirrel monkeys were studied after microiontophoretic injections of biotinylated dextran amine under electrophysiological guidance. A total of 29 axons connected to their parent cell body were entirely reconstructed from serial sections with a camera lucida. Our investigation shows that the CM and Pf nuclei in primates comprise three types of projection neurons: (1) neurons that innervate densely and focally the striatum; (2) neurons that arborize diffusely in the cerebral cortex; and (3) neurons that innervate both striatum and cerebral cortex. Striatal innervation of CM origin consists of dense clusters of axon terminals exhibiting pedunculated varicosities and forming oblique bands in the dorsolateral sector of putamen (sensorimotor striatal territory). The same type of striatal innervation occurs in the head of caudate nucleus (associative striatal territory) in cases of Pf-labeled neurons. The CM neurons that target cerebral cortex arborize principally in motor and premotor areas, whereas Pf neurons innervate chiefly prefrontal areas. Cortical innervation from both nuclei is much more profuse in layers V and VI than in layer I. Our three-dimensional reconstruction studies show that dendritic and axonal arborizations of CM neurons extend essentially along the sagittal plane. These results revealed that, in contrast to rodents where virtually all Pf neurons project to both striatum and cortex, the primate CM/Pf complex harbors several types of highly patterned projection neurons. As such, this complex might be considered as an integral part of the widely distributed basal ganglia neuronal system.     

Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum

The connections between host corticostriatal afferents and neurons in intrastriatal grafts of foetal striatal tissue have been studied with electron microscopic immunocytochemistry using Phaseolus vulgaris leucoagglutinin (PHA-L) as a label of the host corticostriatal fibres. Adult rats with unilateral ibotenic acid lesions of the head of the caudate putamen received foetal cell suspension grafts from E14-15 rat embryos into the lesioned striatal area. Ten months after transplantation, multiple iontophoretic injections of PHA-L were made into the host frontal cortex. These injections labelled large numbers of corticostriatal fibres which extended across the graft - host border to form a rich axonal network mainly in the peripheral portions of the grafts. At the ultrastructural level a total of 134 PHA-L-labelled terminals were identified to form asymmetric synaptic contacts with neurons within the grafts. Of these contacts, 83% were in contact with dendritic spines, 12% with dendritic shafts, and 5% with small shafts or spines. The synaptic contacts were similar to those identified in intact regions of the host striatum that were spared by the lesion. However, the synapses in the host striatum were almost exclusively in contact with spines (98%). These results demonstrate that the corticostriatal projection, which constitutes a major source of afferent control in the normal striatum, not only extends axons into the intrastriatal striatal grafts, but also establishes synaptic connections with the implanted neuronal elements.     

Laminar Origin of Corticostriatal Projections to the Motor Putamen in the Macaque Brain

In the macaque brain, projections from distant, interconnected cortical areas converge in specific zones of the striatum. For example, specific zones of the motor putamen are targets of projections from frontal motor, inferior parietal, and ventrolateral prefrontal hand-related areas and thus are integral part of the so-called “lateral grasping network.” In the present study, we analyzed the laminar distribution of corticostriatal neurons projecting to different parts of the motor putamen. Retrograde neural tracers were injected in different parts of the putamen in 3 Macaca mulatta (one male) and the laminar distribution of the labeled corticostriatal neurons was analyzed quantitatively. In frontal motor areas and frontal operculum, where most labeled cells were located, almost everywhere the proportion of corticostriatal labeled neurons in layers III and/or VI was comparable or even stronger than in layer V. Furthermore, within these regions, the laminar distribution pattern of corticostriatal labeled neurons largely varied independently from their density and from the projecting area/sector, but likely according to the target striatal zone. Accordingly, the present data show that cortical areas may project in different ways to different striatal zones, which can be targets of specific combinations of signals originating from the various cortical layers of the areas of a given network. These observations extend current models of corticostriatal interactions, suggesting more complex modes of information processing in the basal ganglia for different motor and nonmotor functions and opening new questions on the architecture of the corticostriatal circuitry.SIGNIFICANCE STATEMENT Projections from the ipsilateral cerebral cortex are the major source of input to the striatum. Previous studies have provided evidence for distinct zones of the putamen specified by converging projections from specific sets of interconnected cortical areas. The present study shows that the distribution of corticostriatal neurons in the various layers of the primary motor and premotor areas varies depending on the target striatal zone. Accordingly, different striatal zones collect specific combinations of signals from the various cortical layers of their input areas, possibly differing in terms of coding, timing, and direction of information flow (e.g., feed-forward, or feed-back).     

The early development of major projections to the dorsal striatum in the North American opossum

We have employed immunocytochemical and axonal transport techniques to study the development of major projections to the dorsal striatum of the North American opossum. The opossum is born in a very immature state, 12-13 days after conception, and climbs into an external pouch where it remains attached to a nipple for several months. Its immaturity at birth and its protracted postnatal development make the opossum a good model for developmental studies. Although tyrosine hydroxylase-like immunoreactive (TH-LI), presumably dopaminergic, neurons were present in the ventral mesencephalon at birth (the presumptive substantia nigra and ventral tegmental area), there was no evidence for TH-LI axons in the striatal anlage. By postnatal day (PD)6, a few immunostained axons were found within the putamen. The subsequent growth of TH-LI axons into the striatum followed general caudal to rostral and ventrolateral to dorsomedial gradients and, at any age, they were most numerous in the areas exhibiting the greatest cytodifferentiation. By estimated (E)PD45, TH-LI axons were present in most, if not all, areas of the striatum. Serotoninergic (5-HT)-LI axons were found lateral to the presumptive striatum at birth but not within it. By PD7, however, a few 5-HT-LI axons could be identified in the putamen. The growth of 5-HT-LI axons into the striatum generally followed the same gradients described for TH-LI axons although at all ages their density was much less. Using the orthograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), evidence was obtained for the existence of thalamostriatal projections by PD5 and for corticostriatal projections by PD10. Crossed corticostriatal projections were present by EPD23. Our results suggest that the development of major projections to the striatum occurs postnatally in the opossum, rather than prenatally as in placental animals. The timetable for striatal innervation is discussed in light of the developmental sequences established for other motor circuits.     

Cells of origin and terminal distribution of corticostriatal fibers arising in the sensory-motor cortex of monkeys.

The cells of origin of the corticostriatal projection have been identified in squirrel monkeys by the use of the retrograde horseradish peroxidase method. In the subfields of the somatic sensory, motor, parietal and frontal areas of the cortex, cells projecting to the ipsilateral striatum are relatively sparsely distributed and form a group of small- to medium-sized pyramidal cells with an average somal diameter from area to area of 14-16 mum. Such cells are found only in layer V of the cortex (mainly in the more superficial parts of the layer). Since they are consistently smaller than the pyramidal cells of layer V that project to the brainstem and spinal cord and since they lie outside layer VI which gives rise to corticothalamic axons, the corticostriatal axons are unlikely to be collaterals of axons projecting to other sites. The cells of origin of the crossed corticostriatal projection are also found in layer V and are pyramidal cells with somal diameters in the same range as above. They are found only in areas 4, 8, and 6. Studies with the anterograde, autoradiographic method in rhesus, cynomologous and squirrel monkeys, indicate that the somatic sensory areas project to most of the antero-posterior extent of the ipsilateral putamen. Subareas 3a, 3b, 1 and 2 of the somatic sensory cortex project to the same region and the projection overlaps similarly extensive projections from the motor and certain other areas of the cortex. However, in each case the pattern of terminal labeling is in the form of interrupted clusters, strips and bands. A single small injection of the cortex is associated with only one or two such clusters of terminal labeling. This seems to imply that individual corticostriatal fibers end in a very restricted manner and that the terminal ramifications of fibers from one cortical area may alternate in the putamen with those arising in other areas.     

The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat

The frontal cortex provides strong excitatory inputs to the subthalamic nucleus (STN), and these cortico-STN inputs play critical roles in the control of basal ganglia activity. It has been assumed from anatomical and physiological studies that STN is innervated mainly by collaterals of thick and fast conducting pyramidal tract axons originating from the frontal cortex deep layer V neurons, implying that STN directly receives efferent copies of motor commands. To more closely examine this assumption, we performed biotinylated dextran amine anterograde tracing studies in rats to examine the cortical layer of origin, the sizes of parent axons, and whether or not the cortical axons emit any other collaterals to brain areas other than STN. This study revealed that the cortico-STN projection is formed mostly by collaterals of a small fraction of small-to-medium-sized long-range corticofugal axons, which also emit collaterals that innervate multiple other brain sites including the striatum, associative thalamic nuclei, superior colliculus, zona incerta, pontine nucleus, multiple other brainstem areas, and the spinal cord. The results imply that some layer V neurons are involved in associative control of movement through multiple brain innervation sites and that the cortico-STN projection is one part of this multiple corticofugal system.     

Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque

This study examines the organization of thalamostriatal projections from ventral tier nuclei that relay basal ganglia output to the frontal cortex. Although previous thalamostriatal studies emphasize projections from the intralaminar nuclei, studies in primates show a substantial projection from the ventral anterior (VA) and ventral lateral (VL) nuclei. These nuclei make up the main efferent projection from the basal ganglia to frontal cortical areas, including primary motor, supplementary, premotor, and cingulate motor areas. Functionally related motor areas of the frontal cortex and VA/VL have convergent projections to specific regions of the dorsal striatum. The distribution of VA/VL terminals within the striatum is crucial to understanding their relationship to motor cortical afferents. We placed anterograde tracer injections into discrete VA/VL thalamic areas. VA/VL thalamostriatal projections terminate in broad, rostrocaudal regions of the dorsal striatum, corresponding to regions innervated by functionally related cortical motor areas. The pars oralis division of VL projects primarily to the dorsolateral, postcommissural putamen, whereas the parvicellular VA targets more medial and rostral putamen regions, and the magnocellular division of VA targets the dorsal head of the caudate nucleus. Whereas these results demonstrate a general functional topography, specific VA/VL projections overlap extensively, suggesting that functionally distinct VA/VL projections may also converge in dorsal striatal areas. Within striatal territories, VA/VL projections terminate in a patchy, nonhomogeneous manner, indicating another level of complexity. Moreover, terminal fields contain both terminal clusters and scattered, long, unbranched fibers with many varicosities. These fiber morphologies resemble those from the cortex and raise the possibility that VA/VL thalamostriatal projections neurons have divergent connectional features.     

Corticothalamic projections from layer V cells in rat are collaterals of long-range corticofugal axons

The vast majority of corticothalamic (CT) axons projecting to sensory-specific thalamic nuclei arise from layer VI cells but intralaminar and associative thalamic nuclei also receive, to various degrees, a cortical input from layer V pyramidal cells. It is also well established that all long-range corticofugal projections reaching the brainstem and spinal cord arise exclusively from layer V neurons. These observations raise the possibility that the CT input from layer V cells may be collaterals of those long-range axons projecting below thalamic level. The thalamic projections of layer V cells were mapped at a single cell level following small microiontophoretic injections of biocytin performed in the motor, somatosensory and visual cortices in rats. Camera lucida reconstruction of these CT axons revealed that they are all collaterals of long-range corticofugal axons. These collaterals do not give off axonal branches within the thalamic reticular nucleus and they arborize exclusively within intralaminar and associative thalamic nuclei where they form small clusters of varicose endings. As layer V cells are involved in motor commands everywhere in the neocortex, these CT projections and their thalamic targets should be directly involved in the central organization of motor programs.     

Corticostriatal functional interactions in Parkinson's disease: a rTMS/[11C]raclopride PET study

Several animal studies have shown that striatal dopamine can be released under direct control of glutamatergic corticostriatal efferents. In Parkinson's disease (PD), abnormalities in corticostriatal interactions are believed to play an important role in the pathophysiology of the disease. Previously, we have reported that, in healthy subjects, repetitive transcranial magnetic stimulation (rTMS) of motor cortex (MC) induces focal dopamine release in the ipsilateral putamen. In the present study, using [11C]raclopride PET, we sought to investigate early PD patients with evidence of unilateral motor symptoms. We measured in the putamen changes in extracellular dopamine concentration following rTMS (intensity, 90% of the resting motor threshold; frequency, 10 Hz) of the left and right MC. The main objective was to identify potential differences in corticostriatal dopamine release between the hemisphere associated with clear contralateral motor symptoms (symptomatic hemisphere) and the presymptomatic stage of the other hemisphere (asymptomatic hemisphere). Repetitive TMS of MC caused a binding reduction in the ipsilateral putamen of both hemispheres. In the symptomatic hemisphere, while the amount of TMS-induced dopamine release was, as expected, smaller, the size of the significant cluster of change in [11C]raclopride binding was, instead, 61.4% greater than in the asymptomatic hemisphere. This finding of a spatially enlarged area of dopamine release, following cortical stimulation, may represent a possible in vivo expression of a loss of functional segregation of cortical information to the striatum and an indirect evidence of abnormal corticostriatal transmission in early PD. This has potential implications for models of basal ganglia function in PD.     

The striatopallidal projection displays a high degree of anatomical specificity in the primate

The striatopallidal projection in the squirrel monkey (Saimiri sciureus) was studied with two highly sensitive anterograde tracers, the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) and biocytin. After small PHA-L injections into various sectors of the striatum, the striatopallidal projection was found to display a very precise topographical organization. Fibers from the head of the caudate nucleus emerge as several distinct fascicles that penetrate the dorsal portion of the pallidum at various points along its rostrocaudal extent. Each fascicle arborizes into the dorsal third of the pallidum as dense plexuses composed of numerous fibers that closely entwined the dendrites of pallidal neurons, hence forming typical 'woolly' fiber arrangements. In contrast, fibers from the postcommissural putamen emerge as a few compact bundles that reach the pallidum through its lateral surface. In the pallidum, thin fibers detach themselves from these compact bundles, sweep caudally, and arborize in the form of narrow and elongated bands aligned parallel to the medullary laminae. Each band appears composed of numerous, thin and weakly varicose fibers that make only en passant type of contact with pallidal cell bodies rostrally, but form a dense field of woolly fibers caudally. In cases in which two PHA-L injections were made at two different rostrocaudal levels in the putamen, two rostrocaudally distant fields of woolly fibers, separated one another by thin varicose fibers, occur in each band. Furthermore, each PHA-L injection site in the striatum gives rise to at least two bands in each pallidal segment, indicating that the primate striatum has a dual representation at pallidal level. Finally, injections of PHA-L and biocytin into two small and mediolaterally adjacent areas of the postcommissural putamen lead to the formation of two clearly distinguishable sets of bands in each pallidal segment. Even though they lie very close to one another these two types of bands never really overlap. This experiment shows that, in contrast to previous beliefs, axons of striatal neurons from two small adjacent populations do not converge upon the same pallidal neurons but instead project to several distinct subsets of pallidal neurons. The findings of the present study reveal that the striatopallidal projection system in primates is highly ordered and displays a high degree of specificity with respect to its target sites in the pallidum. Different anatomical strategies are used to maximally exploit the relatively small pallidal space and ensure that the finely tuned corticostriatal information is not blurred as it flows through the funnel-shaped pallidum.     

Dopamine D2 receptors are present in prefrontal cortical afferents and their targets in patches of the rat caudate-putamen nucleus.

Glutamatergic neurons within the deep layers of the prefrontal cortex and dopaminergic neurons of the substantia nigra pars compacta preferentially terminate in patch-like regions within the caudate putamen nucleus (CPN). Activation of dopamine D2 receptors is known to potently modulate striatal glutamatergic transmission and may play a role in reward-based motor learning. To determine the cellular substrate for D2-mediated regulation of prefrontal corticostriatal transmission in striatal patches, we combined anterograde transport of biotinylated dextran amine (BDA) with immunogold-silver labeling of a D2 receptor antipeptide antiserum in rat brain. Injections centered in deep layers of the dorsal part of the anterior cingulate cortex, one of the prefrontal cortical regions, produced varicose axonal BDA labeling in a patch-like distribution in the dorsomedial CPN. Electron microscopy showed that in these patch compartments, BDA labeling was present exclusively in axons and terminals (total number = 581), 9% of which contained detectable D2-like immunoreactivity. Thirty percent of the BDA-labeled terminals formed asymmetric excitatory synapses with dendritic spine heads, and the remainder were without recognizable junctions. The recipient spines were unlabeled or contained immunogold-silver particles for D2 receptors. A few of the D2-labeled spines also received convergent, often nonsynaptic contact from D2-labeled terminals resembling dopaminergic afferents. In addition, the corticostriatal terminals often apposed spiny and nonspiny neuronal profiles that contained D2 labeling. These results suggest that dopamine D2 receptors are strategically positioned for presynaptic and postsynaptic modulation of prefrontal corticostriatal excitation of spiny neurons in striatal patches. The findings have direct implications for D2-mediated control of reward-related motor learning.     

Corticostriatal connections of extrastriate visual areas in rhesus monkeys

The striatal connections of extrastriate visual areas were examined by the autoradiographic technique in rhesus monkeys. The medial as well as the dorsolateral extrastriate regions project preferentially to dorsal and lateral portions of the head and of the body of the caudate nucleus, as well as to the caudodorsal sector of the putamen. The rostral portion of the annectant gyrus has connections to the caudal sector of the body and to the genu, whereas projections from the caudal portion of the lower bank of the superior temporal sulcus are directed to dorsal and central sectors of the head and the body, to the genu and the tail, as well as to the caudal putamen. The ventrolateral extrastriate region is related mainly to the ventral sector of the body, to the genu and the tail, and to the caudal putamen. In contrast, the striatal projections of the ventromedial extrastriate cortex resemble those of the medial and dorsolateral regions. The caudal inferotemporal cortex is related strongly to the tail of the caudate nucleus and to the ventral putamen. The differential corticostriatal connectivity of the various extrastriate regions may contribute to the specific functional roles of these cortices. Thus, the connections from the dorsomedial, dorsolateral, and ventromedial areas to dorsal portions of the caudate nucleus and of the putamen may serve a visuospatial function. In contrast, the connections from the ventrolateral extrastriate and inferotemporal regions to the tail of the caudate nucleus and to the ventral putamen may have a role in visual object-related processes. © 1995 Wiley-Liss, Inc.     

Organization of the avian “corticostriatal” projection system: A retrograde and anterograde pathway tracing study in pigeons

Birds have well-developed basal ganglia within the telencephalon, including a striatum consisting of the medially located lobus parolfactorius (LPO) and the laterally located paleostriatum augmentatum (PA), Relatively little is known, however, about the extent and organization of the telencephalic “cortical” input to the avian basal ganglia (i. e., the avian “corticostriatal” projection system). Using retrograde and anterograde neuroanatomical pathway tracers to address this issue, we found that a large continuous expanse of the outer pallium projects to the striatum of the basal ganglia in pigeons. This expanse includes the Wulst and archistriatum as well as the entire outer rind of the pallium intervening between Wulst and archistriatum, termed by us the pallium externum (PE). In addition, the caudolateral neostriatum (NCL), pyriform cortex, and hippocampal complex also give rise to striatal projections in pigeon. A restricted number of these pallial regions (such as the “limbic” NCL, pyriform cortex, and ventral/caudal parts of the archistriatum) project to such ventral striatal structures as the olfactory tubercle (TO), nucleus accumbens (Ac), and bed nucleus of the stria terminalis (BNST). Such “limbic” pallial areas also project to medialmost LPO and lateralmost PA, while the hyperstriatum accessorium portion of the Wulst, the PE, and the dorsal parts of the archistriatum were found to project primarily to the remainder of LPO (the lateral two-thirds) and PA (the medial four-fifths). The available evidence indicates that the diverse pallial regions projecting to the striatum in birds, as in mammals, are parts of higher order sensory or motor systems. The extensive corticostriatal system in both birds and mammals appears to include two types of pallial neurons: (1) those that project to both striatum and brainstem (i. e., those in the Wulst and the archistriatum) and (2) those that project to striatum but not to brainstem (i. e., those in the PE). The lack of extensive corticostriatal projections from either type of neuron in anamniotes suggests that the anamniote-amniote evolutionary transition was marked by the emergence of the corticostriatal projection system as a prominent source of sensory and motor information for the striatum, possibly facilitating the role of the basal ganglia in movement control. © 1995 Wiley-Liss, Inc.     

Cadherin‐8 expression,synaptic localization,and molecular control of neuronal form in prefrontal corticostriatal circuits

Neocortical interactions with the dorsal striatum support many motor and executive functions, and such underlying functional networks are particularly vulnerable to a variety of developmental, neurological, and psychiatric brain disorders, including autism spectrum disorders, Parkinson's disease, and Huntington's disease. Relatively little is known about the development of functional corticostriatal interactions, and in particular, virtually nothing is known of the molecular mechanisms that control generation of prefrontal cortex–striatal circuits. Here, we used regional and cellular in situ hybridization techniques coupled with neuronal tract tracing to show that Cadherin‐8 (Cdh8), a homophilic adhesion protein encoded by a gene associated with autism spectrum disorders and learning disability susceptibility, is enriched within striatal projection neurons in the medial prefrontal cortex and in striatal medium spiny neurons forming the direct or indirect pathways. Developmental analysis of quantitative real‐time polymerase chain reaction and western blot data show that Cdh8 expression peaks in the prefrontal cortex and striatum at P10, when cortical projections start to form synapses in the striatum. High‐resolution immunoelectron microscopy shows that Cdh8 is concentrated at excitatory synapses in the dorsal striatum, and Cdh8 knockdown in cortical neurons impairs dendritic arborization and dendrite self‐avoidance. Taken together, our findings indicate that Cdh8 delineates developing corticostriatal circuits where it is a strong candidate for regulating the generation of normal cortical projections, neuronal morphology, and corticostriatal synapses. J. Comp. Neurol. 523:75–92, 2015. © 2014 Wiley Periodicals, Inc.     

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of subcortical projections.

The subcortical projections of the centromedian (CM) and the parafascicular (Pf) thalamic nuclei were examined in the squirrel monkey (Saimiri sciureus) by using the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer. Both CM and Pf project massively to the striatum where they arborize in a complementary fashion. On the one hand, CM innervates most of the putamen caudal to the anterior commissure, a dorsolateral rim of the putamen rostral to the anterior commissure, discrete areas of the head of the caudate nucleus close to the internal capsule, and a lateral sector of the body of the caudate nucleus. On the other hand, Pf provides a heavy input to the head, body, and tail of the caudate nucleus, and to the rostral putamen, excluding the areas innervated by CM. In addition, Pf projects more discretely to the nucleus accumbens and the olfactory tubercle. Therefore, the projections from both CM and Pf cover the entire striatum, with those from CM arborizing into the "sensorimotor" striatal territory and the ones from Pf innervating the "associative-limbic" striatal territory. Furthermore, CM and Pf project to extrastriatal subcortical structures, such as the globus pallidus, the subthalamic nucleus, and the substantia nigra, where they also terminate in a complementary fashion. Topographically and cytologically, Pf is closely related to the subparafascicular nucleus (sPf). The Pf-sPf complex projects to the hypothalamus, the substantia innominata, the peripeduncular nucleus, and the amygdala. It also gives rise to descending efferents arborizing in various brainstem structures, including the inferior olivary complex. Additional studies with retrograde double-labeling methods show that distinct cell groups within CM project to the motor cortex and the striatum. Likewise, separate neuronal populations within the CM-Pf-sPf complex give rise to striatal and brainstem projections, the former arising from CM and Pf and the latter mainly from sPf. The complementary nature of CM and Pf projections to the striatum and other basal ganglia components suggests that this thalamic complex participates in a highly ordered manner in the parallel processing of the information that flows through the basal ganglia.     

Effect of sensory stimulation in rat barrel cortex, dorsolateral striatum and on corticostriatal functional connectivity

The striatum integrates sensory information to enable action selection and behavioural reinforcement. In the rat, a large topographical projection from the rat barrel cortex to widely distributed areas of the striatum is assumed to be an important structural component supporting these processes. The striatal sensory response is, however, not comprehensively understood at a network level. We used a 10-Hz, 100-ms air puff, allowing undamped movement of multiple whiskers, to look at functional connectivity in contralateral cortex and striatum in response to sensory stimulation. Simultaneous recordings of cortical and striatal local field potentials (LFPs) were made under isoflurane anaesthesia in 15 male Brown Norway rats. Four electrodes were placed in the barrel cortex while the dorsolateral striatum was mapped with a 500-μm resolution, resulting in a maximum of 315 recording positions per animal. Significant event-related responses were unevenly distributed throughout the striatum in 34.8% of positions recorded within this area. Only 10.3% of recorded positions displayed significant total power increases in the LFPs during the stimulation period at the stimulus frequency. This suggests that the responses seen in the LFPs are due to phase rearrangement rather than an amplitude increase in the signal. Analysis of corticostriatal imaginary coherence revealed stimulus-induced changes in the functional connectivity of 12% of corticostriatal pairs, the sensory response of sparsely distributed neuronal ensembles within the dorsolateral striatum is reflected in the phase relationship between the cortical and striatal local fields.     

Cortical stimulation induces fos expression in intrastriatal striatal grafts

Innervation of intrastriatal grafts of fetal striatal tissue by host corticostriatal projections has been shown in a number of previous studies in rats. In the work reported here, induction of Fos protein in grafted striatal neurons by electrical stimulation of the host frontoparietal cortex has been used as cell-level marker of corticostriatal postsynaptic responses within the striatal grafts. Unilateral cortical stimulation 30 min before sacrifice led to bilateral widespread and intense Fos induction throughout the normal striatum, although the response was somewhat more intense ipsilaterally and in the dorsolateral rostral striatum. In adult rats whose striatum had been lesioned with ibotenic acid 10–12 days prior to implantation of fetal striatal tissue, 3- and 18-month-old striatal grafts showed Fos immunoreactivity in a considerable number of cells after either bilateral, or ipsilateral (30–40% of the density of Fos-immunoreactive cells in the normal striatum) or contralateral cortical stimulation. Double-Fos and -DARPP-32 immunohistochemistry revealed that the Fos-immunoreactive nuclei were concentrated in the DARPP-32-positive (i.e. striatum-like) patches, which contained 60% of the density of Fos-positive nuclei in the normal striatum after either ipsilateral or bilateral stimulation. However, Fos-immunoreactive nuclei were unevenly distributed within the DARPP-32-positive compartment of the graft, with some clusters of Fos-immunoreactive nuclei at 2−3 × the density observed in the normal striatum and other areas with Fos-immunoreactive nuclei present at lower density or absent. Fos induction was also observed in 4-week-old grafts, indicating that functional corticostriatal synaptic contacts develop rapidly. Striatal grafts implanted either in non-lesioned host striatum or in long-term (18 months) lesioned striatum, similarly showed Fos-positive nuclei after cortical stimulation, indicating that host corticostriatal fibers are equally capable of establishing functional synaptic contacts under these conditions. These results indicate that host corticostriatal fibres not only form an axonal network within the graft but also induce postsynaptic responses which may contribute to the observed graft-induced amelioration of lesion-induced behavioural deficits.     

Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.     

Regulation of the polysialylated form of the neural cell adhesion molecule in the developing striatum: Effects of cortical lesions

Early in development, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is expressed by growth cones, neuronal processes, and neuronal cell bodies. In rat striatum, PSA-NCAM expression becomes progressively restricted to pre- and postsynaptic membranes and is undetectable by postnatal day 25 (P25), i.e., after corticostriatal synaptogenesis. This study examined the effects of cortical lesions performed on P14, when the corticostriatal projection is already primarily unilateral and cortical inputs have not yet formed asymmetric synapses on striatal neurons. Rats were killed on P25, and PSA-NCAM expression was examined by immunoblotting and immunohistochemistry with light and electron microscopy. In contrast to the case in controls, PSA-NCAM expression was maintained in the striatum of lesioned pups. Ultrastructural studies showed that PSA-NCAM was present 1) in growth cone-like structures and neuronal processes and 2) in striatal neurons. Together with the presence of growth cones, the observation that the number of asymmetric synapses was unchanged in the denervated striatum suggests that axonal sprouting occurred in response to the lesion. This was confirmed by axonal labeling in the denervated striatum after injection of Fluoro-Ruby in the contralateral cortex. The data indicate that P14 cortical lesions affect PSA-NCAM expression in the developing striatum 1) by inducing a robust axonal plasticity resulting in the presence of immature presynaptic elements that contain PSA-NCAM and 2) by delaying the loss of PSA-NCAM expression in striatal neurons, suggesting that the lesion affects the time course of striatal maturation. J. Comp. Neurol. 389:289–308, 1997. © 1997 Wiley-Liss, Inc.     

Lesion of the ventromedial nucleus of the thalamus blocks acute cocaine‐induced changes in striatal glutamate

A single injection of cocaine increases extracellular glutamate in the rat dorsolateral striatum 1 day after the acute cocaine was administered (McKee and Meshul, 2005). However, the nuclei that facilitate this increase in striatal glutamate remain unknown. We hypothesized that the cocaine‐induced increase in striatal glutamate was produced by activation of the ventromedial (VM) nucleus of the thalamus via the thalamo‐corticostriatal or thalamostriatal pathways. First, rats received an electrolytic lesion of the VM. One day after a single cocaine or vehicle injection, extracellular glutamate was measured in the dorsolateral striatum using in vivo microdialysis. The motor thalamus lesion blocked the cocaine‐induced increase in striatal glutamate and reduced extracellular glutamate to the level of the vehicle‐treated group. This study shows a critical role for the VM nucleus of the thalamus in mediating the effects of cocaine on extracellular glutamate levels in the rat dorsolateral striatum. Synapse 64:445–448, 2010. © 2010 Wiley‐Liss, Inc.