Organization of visual corticostriatal projections in the cat,with observations on visual projections to claustrum and amygdala

Electrophysiological mapping criteria were employed to identify visual areas 20a, 20b, 21a, 21b, PMLS, AMLS, ALLS, PLLS, DLS, VLS, and PS in the cat, and to guide placement of tracer deposits. Anterograde tracer methods were used to study the corticostriatal projections of these extrastriate visual areas. The experiments demonstrate that all 11 extrastriate areas send projections to two distinct regions within the striatum, an extensive longitudinal zone within the caudate nucleus, and a more compact region within the posterolateral putamen. Cortical visual projections to the putamen terminate in relatively compact sheets or slabs, and appear to overlap extensively, while those to the caudate nucleus are irregularly patchy and more widely dispersed. Retrograde tracer deposits into the visual recipient zone of the caudate nucleus reveal substantial convergence of other cortical inputs to this same domain. Aspects of visuotopic organization are preserved in the visual projections to both the putamen and the caudate nucleus, but unequivocal retinotopic organization could not be inferred from the available material. Ten of the eleven extrastriate visual area also project topographically onto the visual zone of the claustrum. Area PS does not appear to contribute to the corticoclaustral projections. Five of the extrastriate visual areas (ALLS, PLLS, DLS, VLS, PS) also send sparse projections to the amygdaloid complex. c 1993 Wiley-Liss, Inc.     

Dysfunction of the corticostriatal pathway in autism spectrum disorders

The corticostriatal pathway that carries sensory, motor, and limbic information to the striatum plays a critical role in motor control, action selection, and reward. Dysfunction of this pathway is associated with many neurological and psychiatric disorders. Corticostriatal synapses have unique features in their cortical origins and striatal targets. In this review, we first describe axonal growth and synaptogenesis in the corticostriatal pathway during development, and then summarize the current understanding of the molecular bases of synaptic transmission and plasticity at mature corticostriatal synapses. Genes associated with autism spectrum disorder (ASD) have been implicated in axonal growth abnormalities, imbalance of the synaptic excitation/inhibition ratio, and altered long-term synaptic plasticity in the corticostriatal pathway. Here, we review a number of ASD-associated high-confidence genes, including FMR1, KMT2A, GRIN2B, SCN2A, NLGN1, NLGN3, MET, CNTNAP2, FOXP2, TSHZ3, SHANK3, PTEN, CHD8, MECP2, DYRK1A, RELN, FOXP1, SYNGAP1, and NRXN, and discuss their relevance to proper corticostriatal function.     

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.     

Prolonged neglect following unilateral disruption of a prefrontal cortical-dorsal striatal system

We investigated the potential function of the system formed by connections between the medial prefrontal cortex and the dorsomedial striatum in aspects of attentional function in the rat. It has been reported previously that disconnection of the same corticostriatal circuit produced marked deficits in performance of a serial, choice reaction-time task while sparing the acquisition of an appetitive Pavlovian approach behaviour in an autoshaping task (Christakou et al., 2001). Here, we hypothesized that unilateral disruption of the same circuit would lead to hemispatial inattention, contrasting with the global attention deficit following complete disconnection of the system. Combined unilateral lesions of the medial prefrontal cortex (mPFC) and the medial caudate-putamen (mCPu) within the same hemisphere produced a severe and long-lasting contralesional neglect syndrome while sparing the acquisition of autoshaping. These results provide further evidence for the involvement of the medial prefrontal-dorsomedial striatal circuit in aspects of attentional function, as well as insight into the nature of neglect deficits following lesions at different levels within corticostriatal circuitry.     

Functional circuits mediating sensorimotor integration: quantitative comparisons of projections from rodent barrel cortex to primary motor cortex, neostriatum, superior colliculus, and the pons

Motor performance depends on somatosensory feedback, and consistent with this finding, primary somatosensory (SI) cortex projects to several regions involved in motor control. Although the pathways mediating sensorimotor integration are known, few studies have compared their projection patterns. Therefore, in each animal, we injected two anterograde tracers into SI barrel cortex and compared the relative density and spatial extent of the labeled projections to the primary motor (MI) cortex, neostriatum, superior colliculus, and basal pons. Quantitative analysis revealed that these projections terminated most extensively in the neostriatum, to a lesser extent in MI cortex, and innervated the least amount of neuropil in the superior colliculus and pontine nuclei. Tracer overlap in the pontine nuclei was significantly higher than in the other three brains regions, and was strongly correlated with overlap in the superior colliculus, presumably because some projections to these two brain regions represent collaterals of the same neurons. The density of labeled varicosities was highest in the pons and lowest in MI. As a proportion of total labeling, densely packed clusters of labeled terminals were most prevalent in the pons, less prevalent in neostriatum and superior colliculus, and least prevalent in MI cortex. These results are consistent with physiological evidence indicating strong coherence between SI barrel cortex and the cerebellum during whisking behavior.     

Enhancement of glutamate release in the rat striatum following electrical stimulation of the nigrothalamic pathway

The release of unlabelled amino acids and newly synthesized [3H]dopamine was estimated in the striatum of halothane-anaesthetized rats superfused using a push-pull cannula. Electrical stimulation of the substantia nigra pars reticulata (SNR), enhanced the release of glutamate (maximal effect +51%) in the ipsilateral striatum. The outflow of [3H]dopamine, aspartate, serine and glutamine was unchanged. Seven-12 days after electrolytic lesion of the ipsilateral ventromedial nucleus of the thalamus SNR, stimulation no longer increased the striatal release of glutamate. It is suggested that electrical stimulation of the SNR enhances the striatal release of glutamate, presumably originating from corticostriatal fibres, by activating a nigrothalamocortical polysynaptic pathway.     

The organization of prefrontocaudate projections and their laminar origin in the macaque monkey: a retrograde study using HRP-gel

The organization of the prefrontocaudate connection in the macaque monkey was studied with a polyacrylamide gel of horseradish peroxidase that was injected, after callosotomy, into the head of the caudate nucleus. Tissues were processed for peroxidase activity with tetramethylbenzidine. Retrogradely labeled cells appeared bilaterally in the prefrontal cortex, and ipsilaterally in the premotor area, frontal operculum, insula, and rostral region of the temporal cortex. In the prefrontal cortex, labeled cells were located in cortical layers 2-6. In layer 2, labeled cells were occasionally seen. In layer 3, a considerable number of labeled cells were seen and were mainly distributed in its lower part. They were pyramidal cells. Layer 4 contained a considerable number of labeled cells that were pyramidal or round. Somal sizes of these labeled cells were from 5 to 15 micron, but none of the cells less than 5 micron were labeled. Layer 5 was densely packed with labeled cells, though at a higher density in its upper part (5a). They were pyramidal cells. In layer 6, pyramidal or fusiform cells were labeled at a lower density than in layer 5. The laminar pattern and density of labeled cells were different among various regions of the prefrontal cortex, but, in general, the supragranular labeling tended to frequently occur in the regions containing the numerous labeled cells. There was a topographical relationship between the prefrontal regions containing the majority of labeled cells and the injection sites in the head of the caudate nucleus: the medial orbitofrontal cortex and the medial surface extending downward from the rostral sulcus project ipsilaterally to the medialmost portion of the ventromedial part of the head of the nucleus, the lateral orbitofrontal cortex projects to the ventromedial part of the head of the nucleus, and the dorsolateral prefrontal cortex ventral to the principal sulcus projects to the central part of the head of the nucleus. Our findings in the macaque monkey indicate that the corticocaudate connection is similar in laminar organization of efferent neurons to the corticocortical connections.     

D1 and D2 Receptor Gene Expression in the Rat Frontal Cortex: Cellular Localization in Different Classes of Efferent Neurons

The dopaminergic input to the frontal cortex has an important role in motor and cognitive functions. These effects are mediated by dopamine receptors both of type D1 and of type D2, although the neural circuits involved are not completely understood. We used in situ hybridization to determine the cellular localization of D1 and D2 receptor mRNAs in the rat frontal cortex. Retrograde tracing was used in the same animals to identify the main cortical efferent populations. Fluorogold was injected into the different cortical targets of the frontal cortex and sections were hybridized with D1 and D2 ³⁵S-labelled cRNA probes. D1 and D2 mRNA-containing neurons were present in all the cortical areas investigated, with greater expression in the medial prefrontal, insular and cingulate cortexes and lower expression in the motor and parietal cortexes. Neurons containing D1 mRNA were most abundant in layer Vlb; they were also present in layers Vla and V of all cortical layers and in layer II of the medial prefrontal, cingulate and insular areas. Double labelling with fluorogold demonstrated that D1 mRNA was present in corticocortical, corticothalamic and corticostriatal neurons. Neurons containing D2 mRNA were essentially restricted to layer V, but only in corticostriatal and corticocortical neurons. Neither D1 nor D2 mRNA was found in corticospinal or corticopontine neurons. The present results demonstrate that D1 and D2 receptor genes are expressed in efferent cortical populations, with higher expression for D1. In spite of an overlap in some cortical layers, the expression of D1 and D2 receptor genes is specific for different categories of pyramidal neurons.     

Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia

Metabotropic glutamate receptors (mGluRs), which couple glutamate to second messengers, have important roles in the regulation of movement by the basal ganglia. We used two polyclonal antisera to mGluR1a and mGluR2/3 and confocal laser microscopy to investigate the localization of these receptors in the basal ganglia of the rat. The mGluRs were visualized in combination with an antibody to tyrosine hydroxylase (TH), an antibody to microtubule-associated protein 2 (MAP2, a dendritic marker), or SV2 (an antibody to a protein associated with presynaptic terminals). In the neostriatum, punctate mGluR1a immunoreactivity (ir) was present in the neuropil. This staining did not colocalize with MAP2-ir or SV2-ir and was not altered by decortication or unilateral 6-hydroxydopamine (6-OHDA) lesions. In the globus pallidus and substantia nigra pars reticulata, however, mGluR1a-ir was tightly clustered along large MAP2-ir dendrites. In contrast to the variations in mGluR1a-ir staining, similar punctate neuropil mGluR2/3-ir staining was observed within all basal ganglia structures. In the neostriatum, these puncta were abundant; unlike mGluR1a, many mGluR2/3-ir puncta colocalized with SV2-ir, and striatal mGluR2/3-ir puncta were markedly reduced in number after decortication. Neither mGluR1a-ir nor mGluR2/3-ir could be detected in TH-ir soma within substantia nigra pars compacta, or in TH-ir striatal terminals. Overall, our observations suggest that mGluR1a and mGluR2/3 receptors have distinct cellular localizations in different components of the basal ganglia circuitry and are likely to subserve distinct functions. Our data support the presence of mGluR2/3 on the terminals of corticostriatal afferents, where they may regulate glutamate release. In contrast, mGluR1a appears to be a postsynaptic receptor of neurons in the neostriatum, globus pallidus, and substantia nigra pars reticulata. J. Comp. Neurol. 390:5–19, 1998. © 1998 Wiley-Liss, Inc.     

Intermittent theta‐burst stimulation rescues dopamine‐dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism: Possible role of glial activity

Background : Recent studies support the therapeutic utility of repetitive transcranial magnetic stimulation in Parkinson's disease (PD), whose progression is correlated with loss of corticostriatal long‐term potentiation and long‐term depression. Glial cell activation is also a feature of PD that is gaining increasing attention in the field because astrocytes play a role in chronic neuroinflammatory responses but are also able to manage dopamine (DA) levels. Methods : Intermittent theta‐burst stimulation protocol was applied to study the effect of therapeutic neuromodulation on striatal DA levels measured by means of in vivo microdialysis in 6‐hydroxydopamine‐hemilesioned rats. Effects on corticostriatal synaptic plasticity were studied through in vitro intracellular and whole‐cell patch clamp recordings while stepping test and CatWalk were used to test motor behavior. Immunohistochemical analyses were performed to analyze morphological changes in neurons and glial cells. Results : Acute theta‐burst stimulation induced an increase in striatal DA levels in hemiparkinsonian rats, 80 minutes post‐treatment, correlated with full recovery of plasticity and amelioration of motor performances. With the same timing, immediate early gene activation was restricted to striatal spiny neurons. Intense astrocytic and microglial responses were also significantly reduced 80 minutes following theta‐burst stimulation. Conclusion : Taken together, these results provide a first glimpse on physiological adaptations that occur in the parkinsonian striatum following intermittent theta‐burst stimulation and may help to disclose the real potential of this technique in treating PD and preventing DA replacement therapy‐associated disturbances. © 2017 International Parkinson and Movement Disorder Society