Morphology and synaptic connections of crossed corticostriatal neurons in the rat

The neurons of origin of the bilateral corticostriatal projection arising from the medial agranular cortical field in rats were identified by antidromic activation from contralateral neostriatal stimulation. The same cells were tested for antidromic activation from the contralateral neocortex and for orthodromic responses to stimulation of neocortex of the contralateral hemisphere or ipsilateral rostral thalamus. The neurons were then stained by intracellular injection of horseradish peroxidase. The laminar distribution of these neurons was compared to that of cortical cells stained retrogradely after injection of wheat germ agglutinin/HRP in the ipsilateral or contralateral neostriatum. The morphological features of physiologically identified corticostriatal neurons, their laminar organization, and their responses to stimulation were examined and compared with crossed corticocortical and brainstem-projecting cells. Crossed corticostriatal cells of the medial agranular cortical field were medium-sized pyramidal neurons found in the superficial part of layer V and in the deep part of layer III. Their basilar dendritic fields and initial intracortical axon collateral arborizations were coextensive with the layer defined by the distribution of corticostriatal neurons. The apical dendrites were thin and sparsely branched but consistently reached layer I, where they made a small arborization. These morphological features were shared by cortical neurons projecting to contralateral neocortex but not responding antidromically to stimulation of contralateral neostriatum, but they were not shared by brainstem-projecting cortical cells. Orthodromic responses to contralateral cortical stimulation consisted of brief excitatory postsynaptic potentials that were followed by powerful and longer-lasting inhibitory postsynaptic potentials. Corticostriatal cells also exhibited small excitatory postsynaptic potentials in response to thalamic stimulation. Many crossed corticostriatal neurons were also commissural corticocortical neurons. The results of reciprocal collision tests showed that this was due to the existence of two separate axonal branches, one projecting to contralateral neocortex and one to contralateral neostriatum. Intracellular staining of these neurons revealed ipsilateral axonal projections to the neostriatum and cortex.     

Cryoanethesia on postnatal day 1, but not day 10, affects adult behavior and cortical morphology in rats

Hypothermia was used to induce anesthesia in infant rats on postnatal days 1 or 10. In adulthood measures of spatial learning and activity were taken before the brains were harvested for measurement of cortical thickness and dendritic arborization in layer III pyramidal cells in parietal cortex. Cryoanethesia on day 1, but not day 10, produced a small, but statistically significant, impairment in learning a spatial navigation task as well as a reduction in cortical thickness and dendritic arborization. This study confirms that cryoanesthesia is not a benign treatment in newborn pups but appears to be without effect in older animals. It is important that all studies using cryoanesthesia have sham control animals exposed to the same degree of hypothermia.     

Chronic (-) deprenyl administration alters dendritic morphology of layer III pyramidal neurons in the prefrontal cortex of adult Bonnett monkeys

Chronic (-) deprenyl (0.2 mg/kg, b.wt; for 25 days) treatment induced alterations in the dendritic morphology of prefrontal cortical neurons in adult Bonnett monkeys were evaluated in the present study. The branching points and intersections in apical and basal dendrites were studied up to a distance of 400 and 200 micrometers, respectively, in Golgi impregnated layer III pyramidal neurons of the prefrontal cortex. Our results revealed a significant (p<0.001) increase in the number of branching points and intersections in both apical and basal dendrites in (-) deprenyl treated monkeys compared to controls. Such an enriched dendritic arborization in prefrontal cortical neurons may be responsible for the enhancement of cognitive functions in Alzheimer disease patients following (-) deprenyl treatment.     

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.     

Topography of cortico-striatal connections in man: anatomical evidence for parallel organization

Tracing studies in non-human primates support the existence of several parallel neuronal circuits involving cerebral cortex, basal ganglia and thalamus. Distinct functional loops were proposed to underlie multiple aspects of normal and pathological behaviour in man. We present here the first anatomical evidence for separate corticostriatal systems in humans. Neural connections of the sensorimotor and prefrontal cortex to the striatum were studied in one human brain using the Nauta method for anterogradely degenerating axons. Axons originating from a lesion in the left sensorimotor cortex, including the face area, were found to terminate in the superolateral part of the ipsilateral putamen, forming a narrow band in its posterior part. Inside the band, the distribution of degenerating axons was inhomogeneous; high-density clusters of approximately 2.5 mm in diameter were separated by regions with less dense cortical projections. Axons originating from a small lesion in the fundus of the right superior frontal sulcus were found in the upper part of the ipsilateral caudate nucleus. The existence of discrete and anatomically segregated terminal patches originating from distinct cortical regions suggests parallel organization of cortico-striatal connections in man.     

Who's on first? What's on second? The time course of learning in corticostriatal systems

The prefrontal cortex and basal ganglia are known to be crucial for learning arbitrary sensorimotor associations (e.g. knowing to stop at red traffic lights). However, little is known about the timing of learning-related activity in these brain systems. Conventional wisdom suggests that the prefrontal cortex should drive learning-related changes in the basal ganglia. However, it is possible that the basal ganglia are instead responsible for the development of learning-related activity in prefrontal cortex. Indeed, recent work using methods for recording in the prefrontal cortex and basal ganglia simultaneously suggests that learning-related activity emerges first in the basal ganglia. Here, these studies are reviewed and integrated with the known anatomy of corticostriatal connections. Testable hypotheses regarding corticostriatal interactions during learning are proposed.     

Recovery from early cortical damage in rats: IV. Effects of hemidecortication at 1, 5 or 10 days of age on cerebral anatomy and behavior

Rats with complete removal of the neocortex of one hemisphere in adulthood (hemidecorticate) were compared behaviorally and anatomically with rats with similar removals at 1, 5, or 10 days of age. There was an unexpected relationship between cortical thickness in adulthood and age at surgery: the earlier the lesion the thicker the cortex. At the two extremes rats hemidecorticated in adulthood had a reduction of up to 10% in the contralateral hemisphere, rats with hemidecortications on the day of birth had cortex that was thicker than adult operates. Behaviorally, the animals were administered several tests including a spatial navigation task, tests of beam walking and swimming, tests of turning bias, and a measure of claw cutting. The main finding was that although the hemidecortication at all ages produced a reliable behavioral change on all measures, the neonatal hemidecorticates performed better than the adults. Further, the earlier the lesion, the better the animals performed. These results are contrasted with the effects of bilateral frontal or parietal neocortical removals in infancy where the earliest lesions have the most severe effect on cortical thickness and behavior. This comparison shows that unilaterality of brain damage is an important factor in predicting recovery or sparing of function from early lesions.     

Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage.

Unilateral lesions to the forelimb representation (FL) area of the rat sensorimotor cortex caused a time-dependent increase in the dendritic arborization of layer V pyramidal neurons in the contralateral homotopic cortex. The increase in arborization was maximum at 2-3 weeks after the lesion, following which there was a partial reduction in dendritic branching. These neural morphological changes may be related to post-lesion behavioral changes in the use of the forelimbs.     

A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia.

BACKGROUND: As a test of plausibility for the hypothesis that schizophrenia can result from abnormal brain, especially cerebral cortical, development, these studies examined whether, in the rat, disruption of brain development initiated on embryonic day (E) 17, using the methylating agent methylazoxymethanol acetate (MAM), leads to a schizophrenia-relevant pattern of neural and behavioral pathology. Specifically, we tested whether this manipulation leads to disruptions of frontal and limbic corticostriatal circuit function, while producing schizophrenia-like, region-dependent reductions in gray matter in cortex and thalamus. METHODS: In offspring of rats administered MAM (22 mg/kg) on E17 or earlier (E15), regional size, neuron number and neuron density were determined in multiple brain regions. Spontaneous synaptic activity at prefrontal cortical (PFC) and ventral striatal (vSTR) neurons was recorded in vivio. Finally, cognitive and sensorimotor processes mediated by frontal and limbic corticostriatal circuits were assessed. RESULTS: Adult MAM-E17-exposed offspring showed selective histopathology: size reductions in mediodorsal thalamus, hippocampus, and parahippocampal, prefrontal, and occipital cortices, but not in sensory midbrain, cerebellum, or sensorimotor cortex. The prefrontal, perirhinal, and occipital cortices showed increased neuron density with no neuron loss. The histopathology was accompanied by a disruption of synaptically-driven "bistable membrane states" in PFC and vSTR neurons, and, at the behavioral level, cognitive inflexibility, orofacial dyskinesias, sensorimotor gating deficits and a post-pubertal-emerging hyper-responsiveness to amphetamine. Earlier embryonic MAM exposure led to microcephaly and a motor phenotype. CONCLUSIONS: The "MAM-E17" rodent models key aspects of neuropathology in circuits that are highly relevant to schizophrenia.     

Fronto-striatal disconnection disrupts operant delayed alternation performance in the rat

The hypothesis that an intact corticostriatal system is necessary to mediate accurate performance of an operant version of a classic prefrontal cortical task, delayed alternation, is tested using a crossover lesion paradigm in rats. Following an initial midline transection of the genu of the corpus callosum to separate the hemispheres, crossed lesions of the striatum in one hemisphere and the prefrontal cortex in the other produced a significant and stable impairment in delayed alternation performance whereas similar lesions made on the same side had little detectable effect. Accuracy and signal detection analysis of performance across different intertrial intervals indicated that the crossed lesions induced delay-dependent deficits in working memory aspects of corticostriatal function, without changes in low levels of response bias.     

Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans

A landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging-based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.     

Sparing of function after neonatal frontal lesions correlates with increased cortical dendritic branching: a possible mechanism for the Kennard effect.

This study examined the possibility that the presence or absence of behavioral sparing following neonatal frontal lesions might be correlated with changes in the complexity of dendritic branching. Rats were given bilateral frontal lesions in either adulthood, the day of birth, or on day 10. Ninety days later the animals were trained in a spatial navigation task. The animals' brains were then processed for Golgi-Cox staining and the dendritic branching of the pyramidal cells in the parietal cortex was analyzed. Frontal cortical lesions in newborn rats produced a severe behavioral deficit in the water task whereas frontal removal at 10 days of age allowed sparing of function relative to adult operates (that is, the Kennard effect). Analysis of dendritic arbor in sensorimotor cortex revealed that the day-10 animals exhibited a dramatic proliferation of dendritic arbor relative to control rats. In contrast, the day-1 animals had slightly less dendritic branching than control animals. Rats with frontal lesions in adulthood showed a small, but significant, increase in dendritic branching. The correlation between behavioral sparing and the increase in dendritic arborization following neonatal lesions may be illustrative of a general mechanism underlying the Kennard effect.     

Hierarchical connectivity and connection-specific dynamics in the corticospinal-corticostriatal microcircuit in mouse motor cortex

The generation of purposive movement by mammals involves coordinated activity in the corticospinal and corticostriatal systems, which are involved in different aspects of motor control. In the motor cortex, corticospinal and corticostriatal neurons are closely intermingled, raising the question of whether and how information flows intracortically within and across these two channels. To explore this, we developed an optogenetic technique based on retrograde transfection of neurons with deletion-mutant rabies virus encoding channelrhodopsin-2, and used this in conjunction with retrograde anatomical labeling to stimulate and record from identified projection neurons in mouse motor cortex. We also used paired recordings to measure unitary connections. Both corticospinal and callosally projecting corticostriatal neurons in layer 5B formed within-class (recurrent) connections, with higher connection probability among corticostriatal than among corticospinal neurons. In contrast, across-class connectivity was extraordinarily asymmetric, essentially unidirectional from corticostriatal to corticospinal. Corticostriatal neurons in layer 5A and corticocortical neurons (callosal projection neurons similar to corticostriatal neurons) similarly received a paucity of corticospinal input. Connections involving presynaptic corticostriatal neurons had greater synaptic depression, and those involving postsynaptic corticospinal neurons had faster decaying EPSPs. Consequently, the three connections displayed a diversity of dynamic properties reflecting the different combinations of presynaptic and postsynaptic projection neurons. Collectively, these findings delineate a four-way specialized excitatory microcircuit formed by corticospinal and corticostriatal neurons. The "rectifying" corticostriatal-to-corticospinal connectivity implies a hierarchical organization and functional compartmentalization of corticospinal activity via unidirectional signaling from higher-order (corticostriatal) to lower-order (corticospinal) output neurons.     

Pattern of corticostriatal innervation in organotypic cocultures is dependent on the age of the cortical tissue

The patch-matrix organization of the striatum is defined by the selective expression of neuronal markers and a semisegregated pattern of afferents and efferents that develops before birth in all mammals. Differential projections from 'limbic' and 'somatomotor' cortices contribute to the selective circuitry of patch ("striosome") and matrix compartments. Organotypic cultures were used to determine the pattern of early corticostriatal innervation as a first step toward understanding the role of cortical innervation in the development of striatal patch-matrix organization. Perinatal striatum (E19-P4) was cocultured with the cortex obtained from same-age or different-age rats in the presence or absence of substantia nigra obtained from E14-15 fetuses. After 4-21 days in vitro, crystals of biocytin were placed directly onto the cortical piece to trace cortical projections into the striatal piece. Cortex obtained from fetuses (E19-22) or neonatal (P0-1) rats gave rise to a dense innervation of both prenatal and postnatal striatal slices; however, the pattern of biocytin-labeled fibers was found to be highly dependent on the age of the cortical tissue used. Cortex derived from rats between E20 and P1 gave rise to a heterogeneous distribution of fibers indicative of striatal patches when combined with striatal slices from same-age or younger (E18-19) fetuses. Cortex from E18-19 fetuses produced a homogeneous innervation even when cocultured with older striatal tissue in which the striatal patches were already present. The postnatal cortex (P2-P5) gave rise to little to no innervation of striatum of all ages. Similar findings were obtained with the use of either prelimbic or somatosensory cortex. In double- and triple-labeled cultures, the distribution of corticostriatal fibers overlapped substantially with patches of developing striatal neurons, as revealed by DARPP-32 immunocytochemistry. Dopaminergic innervation present when the substantia nigra was included in the cocultures also distributed preferentially to the developing patch compartment, but it did not substantially alter the pattern of corticostriatal innervation. These findings suggest that the cortex provides directive signals to the developing striatum rather than simply responding to the presence of patches that have already formed.     

Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns

The cytoarchitecture of the human and the macaque monkey dorsolateral prefrontal cortex has been examined in a strictly comparative manner in order to resolve major discrepancies between the available segmentations of this cortical region in the human and the monkey brain. In addition, the connections of the dorsolateral prefrontal cortical areas were re-examined in the monkey. The present analysis showed that only a restricted portion of what had previously been labelled as area 46 in the monkey has the same characteristics as area 46 of the human brain; the remaining part of this monkey region has the characteristics of a portion of the middle frontal gyrus in the human brain that had previously been included as part of area 9. We have labelled this cortical area as 9/46 in both species. These two areas (i.e. 46 and 9/46), which constitute the lower half of the mid-dorsolateral frontal cortex, have a well-developed granular layer IV, and can easily be distinguished from area 9, on the upper part of the mid-dorsolateral region, which does not have a well-developed granular layer IV. Area 9 has the same basic pattern of connections as areas 46 and 9/46, but, unlike the latter areas, it does not receive input from the lateral parietal cortex. Caudal to area 9, on the dorsomedial portion of the frontal cortex, there is a distinct strip of cortex (area 8B) which, unlike area 9, receives significant input from the prestriate cortex and the medial parietal cortex. The present results provide a basis for a closer integration of findings from functional neuroimaging studies in human subjects with experimental work in the monkey.     

Postsynaptic potentials evoked in spiny neostriatal projection neurons by stimulation of ipsilateral and contralateral neocortex

Postsynaptic potentials were evoked in neostriatal neurons by stimulation of the ipsilateral and contralateral medial agranular frontal cortical field (AGm) in the rat. This cortical region is known to project bilaterally to the dorsal lateral head of the caudate-putamen of rats. Ipsilateral stimulation of AGm should excite all types of corticostriatal neurons projecting to neostriatal neurons in the corresponding area in neostriatum, while stimulation of the same cortical area on the side contralateral to the recording should evoke synaptic potentials from a more restricted subpopulation of crossed corticostriatal neurons. Neostriatal neuronal responses were recorded intracellularly and spiny projection neurons identified by intracellular staining with horseradish peroxidase. The initial EPSP response to contralateral stimulation was similar to that evoked from the ipsilateral side, except for the absence of a relatively small short latency component responsible for the earliest part of the response to ipsilateral cortical stimulation. Comparison with previous findings indicated that this earliest EPSP component was due to activation of fast-conducting descending cortical efferents with collateral projections exclusively to the ipsilateral neostriatum. Stimulation of contralateral neostriatum evoked responses identical to those obtained using stimulation of contralateral neocortex. Analyses of these responses indicated that both EPSPs arise from activation of the same population of fibers. Stimulation of the contralateral internal capsule just caudal to neostriatum was not effective in evoking the EPSP. Chronic hemidecortication did not change the shape of the EPSP evoked from the intact contralateral side, but reduced its amplitude by approximately one half. These observations indicate that contralaterally projecting corticostriatal neurons in the rat project bilaterally in neostriatum, have axonal branches to the contralateral cerebral cortex as well as neostriatum, and converge onto neostriatal neurons that also receive input from the corresponding cortical region on the ipsilateral side.     

Dendritic spines containing μ-opioid receptors in rat striatal patches receive asymmetric synapses from prefrontal corticostriatal afferents

Prefrontal corticostriatal afferents to the caudate-putamen nucleus (CPN) have been implicated in motor and cognitive functions that are subject to opioid modulation through the μ-opioid receptor (MOR). We examined the cellular basis for this modulation by combining anterograde transport of biotinylated dextran amine (BDA) following injections into the rat prefrontal cortex with immunocytochemical detection of MOR in patch compartments of the CPN. The BDA-labeled neurons in deep layer V and layer VI of the dorsal part of the anterior cingulate cortex and the medial agranular cortex projected bilaterally, with an ipsilateral predominance, to MOR-enriched patches in the dorsomedial and dorsocentral CPN, respectively. BDA-labeled terminals often apposed MOR-immunoreactive dendrites and perikarya but formed exclusively asymmetric, excitatory-type synapses mainly with dendritic spines. Of the total anterogradely labeled axon terminals forming asymmetric synapses, 40% (151 of 377) were with MOR-labeled spines, and 58% (220 of 377) were with unlabeled dendritic spines. In addition, immunogold-silver particles for MOR were seen in 14% (134 of 938) of all BDA-labeled axons and axon terminals. These dually labeled axon terminals also formed asymmetric synapses with dendritic spines that contained MOR immunoreactivity. The proportions of BDA-labeled axon terminals forming asymmetric synapses with MOR-labeled or unlabeled spines were similar in the CPN ipsilateral and contralateral to the cortical injections. These results suggest that, in patch compartments of the CPN, MOR plays a critical role in postsynaptic response to, but also in presynaptic modulation of, prefrontal corticostriatal excitation. J. Comp. Neurol. 396:223–237, 1998. © 1998 Wiley-Liss, Inc.     

Consequences of damage to the sensorimotor cortex in neonatal and adult cats. II. Maintenance of exuberant projections

After chronic sensorimotor cortex ablations, sparing and greater recovery of function were seen in neonatally operated cats compared with adult operated cats. These results suggested that undamaged cortex in neonatal operates might display projections different from those of adult operates. Injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) were made in ipsilateral parietal cortex adjacent to the sensorimotor cortex ablations or in the contralateral sensorimotor cortex. No changes in the projections of the parietal cortex were seen in operated cats or in the projections of the undamaged sensorimotor cortical projections of adult operates. In contrast, the intact sensorimotor cortex of neonatal operates exhibited crossed corticothalamic and corticorubral projections not present in normal or adult operated animals, whereas the corticospinal tract (CST) was unchanged by the ablations. Analysis of neurons within the ventroanterior-ventrolateral nuclear complex of the thalamus ipsilateral to the ablation showed that the surviving cells of neonatal operates were equal in number but were, on average, larger than those of normals and adult operates. Some neurons in neonatal operates were larger than any seen in adult operates and normals. Injections of HRP/WGA were also made into the sensorimotor cortex of normal newborn animals. Dense bilateral corticothalamic and corticorubral projections were present. The CST had extended to lumbar levels by the day of birth but projections to the grey matter were sparse. Thus, bilateral projections seen in neonatal operates probably represent retention of some exuberant projections present in normal neonatal animals. The CST which exhibited no exuberant projection was unchanged by the lesion. The crossed corticothalamic and corticorubral projections are likely to play a role in sparing and recovery of function particularly in sparing of contact placing.     

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.     

Ferret pyramidal cell dendritogenesis: changes in morphology and ganglioside expression during cortical development.

Pyramidal cell ontogenesis and basilar dendritic differentiation were evaluated concomitantly with ganglioside expression and distribution in ferret cerebral cortex. Layer V neurons began basilar dendritogenesis on postnatal day 1 (P1) with a peak in dendritic arborization occurring at P21. Layer II/III neurons, in contrast, were in early stages of basilar dendritic differentiation at P14, resulting in a complex dendritic arbor at P28. High performance thin-layer chromatography showed numerous changes in ganglioside expression during cortical development, including a decline of GM2 in the mature cortex. The temporal expression and cellular distribution of GM2, GD2, GM1, GD3, and GM3 gangliosides in developing cerebral cortex were determined by immunocytochemistry. GM2 immunoreactivity (IR) was most prominent in layer V neurons between P1 and P21 and in layer II/III neurons between P14 and P28 with staining diminishing to near absent levels in the adult. GM2-IR appeared as punctate structures within the somatodendritic domain and by electron microscopy was shown to be membrane-bound vesicles often in close proximity to the plasmalemma. Expression of GM2, but not of other gangliosides studied, followed two well-documented developmental neurogenic gradients: ventrolateral to dorsomedial and radial (inside-first outside-last). Onset of significant GD2 expression in layer II/III and V pyramidal cells was delayed until P14 and persisted in adult neocortex. GD3 was localized most prominently to glial-like cells, whereas GM1 was primarily localized to white matter. The close temporal and spatial concordance of GM2-IR in cortical pyramidal neurons undergoing dendritogenesis is consistent with its proposed role as a modulator of dendritic differentiation.