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PubMed1980

Functions of the neostriatum: cortex-dependent or autonomous?

Studies of animals with ablations of varying amounts of the neocortex, the neostriatum, or both, are reviewed in an attempt to establish to which extent functions of the neostriatum are dependent on its cortical input. Scarce and inconclusive evidence does not allow firm conclusions. It seems well established that the neostriatum shares some functions with the neocortex. In the rat and infant monkeys these striatal functions appear to be cortex-independent, whereas in cats and adult monkeys they seem to be more cortex-dependent. It is possible, and even likely, that the neostriatum also has functions which are not shared with the cortex and which are cortex-independent. The degree to which the neostriatum is able to contribute to the integration of behavior in the absence of its cortical input is species- and age-specific.

Animals↗
PubMed2003

Fine structural features of the acetylcholine innervation in the developing neostriatum of rat.

The acetylcholine (ACh) innervation in the developing neostriatum of rat was examined by means of light and electron microscopic immunocytochemistry with a highly sensitive antibody against choline acetyltransferase (ChAT). ChAT-immunoreactive cell bodies and their emerging processes, located at birth in the lateral part of neostriatum, progressively pervaded the whole region, to give rise to an extremely dense axonal network. As visualized and measured in single thin sections, at postnatal (P) ages P8, P16, and P32, the intrinsic and relational features of ChAT-immunostained profiles of axon varicosities in the lateral and medial parts of neostriatum were similar to those previously described in the adult. At the three postnatal ages, the immunoreactive profiles were comparable in shape, size, and vesicular content, and displayed one or more mitochondria with increasing frequency (from 10% at P8 to 29% at P32). The proportion which showed a synaptic junction was low at the three ages (8-16%), indicating an average synaptic incidence of 22% for whole varicosities after stereological extrapolation. The observed junctions were relatively small, mostly symmetrical, and made with dendritic spines or branches. The frequency of synapses on spines versus branches increased with age, from 20% at P8 to almost 60% at P32. Thus, the relational features of the neostriatal ACh innervation were similar to adult as soon as it appeared, as previously observed to be the case in the developing cerebral cortex. The diffuse mode of transmission may therefore be characteristic of both ACh interneurons (neostriatum) and projection neurons (cerebral cortex) in the CNS, and could be determining their functional properties during development as well as at maturity.

Acetylcholine↗
PubMed2006

Topography of cortical projections to the dorsolateral neostriatum in rats: multiple overlapping sensorimotor pathways.

In rodents, the whisker representation in primary somatosensory (SI) cortex projects to the dorsolateral neostriatum, but the location of these projections has never been characterized with respect to layer IV barrels and their intervening septa. To address this issue, we injected a retrograde tracer into the dorsolateral neostriatum and then reconstructed the location of the labeled corticostriatal neurons with respect to the cytochrome oxidase (CO)-labeled barrels in SI. When the tracer was restricted to a small focal site in the neostriatum, the retrogradely labeled neurons formed elongated strips that were parallel to the curvilinear orientation of layer IV barrel rows. After larger tracer injections, labeled neurons were distributed uniformly across layer V and were aligned with both the barrel and septal compartments. Labeled projections from the contralateral SI barrel cortex, however, were much fewer in number and were disproportionately associated with the septal compartments. A comparison of the labeling patterns in the ipsilateral and contralateral hemispheres revealed symmetric, mirror-image distributions that extended across primary motor cortex (MI) and multiple somatosensory cortical regions, including the secondary somatosensory (SII) cortex, the parietal ventral (PV) and parietal rhinal (PR) areas, and the posteromedial (PM) region. Examination of the thalamus revealed labeled neurons in the intralaminar nuclei, in the medial part of the posterior nucleus (POm), and in the ventrobasal complex. These results indicate that the dorsolateral neostriatum integrates sensorimotor information from multiple sensorimotor representations in the thalamus and cortex.

Animals↗
PubMed1995

Parallel pathways and convergence onto HVc and adjacent neostriatum of adult zebra finches (Taeniopygia guttata).

The structure and connectivity of the forebrain nucleus HVc, a site of sensorimotor integration in the song control system of oscine birds, were investigated in adult zebra finches. HVc in males comprises three cytoarchitectonic subdivisions: the commonly recognized central region with large and medium-sized darkly staining cells, a ventral caudomedial region with densely packed small and medium-sized cells, and a dorsolateral region with oblong cells and rows of cells. All three subdivisions project to area X and the robust nucleus of the archistriatum, with more complexity in the classes and distribution of cells than previously reported. In females, HVc is very small and has a cytoarchitecture distinct from that of the three male subdivisions. The structure of HVc in females treated with estradiol at 15 days of age is similar to male HVc. Tracer studies in males with fluorescent and biotinylated dextrans demonstrate non-topographic projections onto HVc that may carry auditory information, including type 1 and type 2 neurons in subdivisions L1 and L3 of the field L complex, a class of neurons in nucleus interface, nucleus uvaeformis, the caudal neostriatum ventral to HVc, and intrinsic HVc connections. These data are interpreted in terms of HVc's functional properties. Additionally, the neostriatum immediately ventral to HVc receives projections from field L, ventral hyperstriatum, and caudal neostriatum, and projects to a region surrounding RA and near to or into area X. The similarity of the connectivity of HVc and adjacent neostriatum suggests the possibility that they share a common origin.

Afferent Pathways↗
PubMed1994

The neostriatum and nucleus accumbens in parkinsonism-dementia complex of Guam: a pathological comparison with Alzheimer's disease and progressive supranuclear palsy.

The neostriatum, nucleus accumbens and basal nucleus of Meynert (bnM) in the parkinsonism-dementia complex of Guam (Guam PDC) were examined immunohistologically, ultrastructurally, quantitatively and topographically, and the results were compared with those in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Compared to neurologically normal controls, the number of large neurons in Guam PDC was reduced by approximately 70% in the caudate nucleus and putamen and by more than 90% in the nucleus accumbens. The decreased number of large neurons in the neostriatum was significantly correlated to that in the bnM. The remaining large neurons and many of the medium-sized neurons in the neostriatum and nucleus accumbens were immunopositive for tau protein and contained varying amounts of 21- to 25-nm-wide paired helical filaments (PHFs) admixed with straight tubules. Curly fibers and circularly arranged reactive astrocytes were seen in the nucleus accumbens of many PDC patients. Collectively, these findings, which are similar in part to those of AD and differ from those of PSP, suggest that the large neurons in the neostriatum and nucleus accumbens in Guam PDC degenerate through PHF formation, and that extremely severe loss of large neurons in the nucleus accumbens may be linked to marked degeneration of the limbic and ventral tegmental areas and nucleus dorsal raphe.

Adult↗
PubMed1994

Repeated treatment with ascorbate or haloperidol, but not clozapine, elevates extracellular ascorbate in the neostriatum of freely moving rats.

Acute administration of neuroleptic drugs alters the extracellular level of ascorbate in the neostriatum, and increasing evidence suggests a role for this vitamin in the behavioral, and possibly therapeutic, effects of these drugs. To shed further light on this issue, extracellular ascorbate was recorded in the neostriatum and nucleus accumbens of awake, behaving rats following chronic treatment with either classical (haloperidol) or atypical (clozapine) neuroleptics or ascorbate itself. Electrochemically modified, carbon-fiber microelectrodes were lowered in place the day after the last of 21 daily injections of either haloperidol (0.5 mg/kg, SC), clozapine (20 mg/kg, IP), sodium ascorbate (500 mg/kg, IP) or vehicle. Voltammetric measurements were obtained during quiet rest and following administration of d-amphetamine (2.5 mg/kg). Repeated treatment with either haloperidol or ascorbate elevated basal extracellular ascorbate and potentiated the amphetamine-induced increase in ascorbate release in neostriatum but not nucleus accumbens. Both treatment groups also showed a significant increase in amphetamine-induced sniffing and repetitive head movements compared to vehicle-treated animals. In contrast, repeated clozapine had no effect on extracellular ascorbate in either neostriatum or nucleus accumbens, but increased the locomotor response to an amphetamine challenge. Thus, to the extent that increases in neostriatal ascorbate exert neuroleptic-like effects, such effects are likely to parallel haloperidol rather than clozapine.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Effects of the cholinergic system of the rat neostriatum on learning active escape in normal animals and in animals with lesions to the intralaminar thalamic nuclei.

Studies were carried out into the role of the parafascicular (Pf) nuclei of the rat thalamus in learning a conditioned active escape reflex (CAER) in a T-maze, a reflex associated with discrimination of visual stimuli, and into the regulatory effect on this learning process of activation of the neostriatal cholinergic system. The following results were obtained using 57 Sprague-Dawley rats divided into a number of experimental groups: 1) bilateral microinjection of carbacholine (0.03 microgram) into the neostriatum on days 4, 5, and 6 of training produced significant (p < 0.01) increases in the proportion of correct discriminant CAER performances; 2) bilateral lesioning of the Pf nuclei led to irreversible disruption of the previously learned CAER. Rats with initially bilaterally lesioned Pf nuclei did not learn the discriminant CAER at all after 10 days of training (16 combinations), and microinjection of carbacholine into the neostriatum of these animals was ineffective. It is concluded that the integrity of the afferent input into the Pf nuclei of the thalamus is an important factor for activation of the neuronal background of the neostriatum, and is required for cholinergic activation of the neostriatum to be effective.

Animals↗
PubMedDate not supplied

Involvement of the parafascicular nucleus of the thalamus and the cholinoreactive system of the neostriatum in controlling a food-procuring reflex in rats at different stages of learning.

A model of a Skinner box food-procuring reflex in rats was used to study the relationship between the strength applied to a pedal and disruption of the parafascicular nucleus of the thalamus and microinjections of the cholinolytic scopolamine and the cholinomimetic carbachol into the neostriatum at different stages of learning. In untrained rats at the stage of learning to press strongly on the pedal without the conditioned signal being switched on (i.e., every strong press was rewarded) showed (a) a decrease in the rate of learning to press strongly and an increase in the number of weak pedal presses after bilateral lesioning of the parafascicular nucleus of the thalamus; (b) that rats with bilateral lesions of this nucleus responded to microinjections of scopolamine into the neostriatum with increases in the number of strong presses, with no change in the number of weak pedal presses, while microinjections of carbachol decreased the number of strong and increased the number of weak presses as compared with the pre-microinjection baseline. In trained rats at the stage of recovery the reflex (i.e., strong pedal presses were reinforced only during exposure to the conditioned signal), lesioning of the parafascicular nucleus of the thalamus had the effect that the time required for recovery of the reflex became dependent on the level of pre-operative training; scopolamine microinjections into the neostriatum of rats achieving high levels of correct performances of the reflex only after surgery led to sharp degradation in performance of the reflex on the day of microinjections; microinjection of carbachol into the neostriatum of rats with low post-operative levels of performance of the reflex had no effect on this measure.

Animals↗
PubMed2000

Dopaminergic denervation enhances susceptibility to hydroxyl radicals in rat neostriatum.

To determine if greater amounts of hydroxyl radical (*OH) are formed by dopamine (DA) denervation and treatment with L-dihydroxyphenylalanine (L-DOPA), the neostriatum was DA denervated (99% reduction in DA content) by 6-hydroxydopamine treatment (134microg icv, desipramine pretreatment) of neonatal rats. At 10 weeks the peripherally restricted dopa decarboxylase inhibitor carbidopa (12.5mg/kg i.p.) was administered 30min before vehicle, L-DOPA (60mg/kg i.p.), or the known generator of reactive oxygen species, 6-hydroxydopa (6-OHDOPA) (60mg/kg i.p.); and this was followed 30min later (and 15 min before termination) by the spin trap, salicylic acid (8micromoles icv). By means of a high performance liquid chromatographic method with electrochemical detection, we found a 4-fold increase in the non-enzymatically formed spin trap product, 2,3-dihydroxybenzoic acid (2,3-DHBA), with neither L-DOPA nor 6-OHDOPA having an effect on 2,3-DHBA content of the neostriatum. Basal content of 2,5-DHBA, the enzymatically formed spin trap product, was 4-fold higher vs. 2,3-DHBA in the neostriatum of untreated rats, while L-DOPA and 6-OHDOPA each reduced formation of 2,5-DHBA. We conclude that DA innervation normally suppresses *OH formation, and that the antiparkinsonian drug L-DOPA has no effect (2,3-DHBA) or slightly reduces (2,5-DHBA) *OH formation in the neostriatum, probably by virtue of its bathing the system of newly formed *OH.

Animals↗
PubMed2006

Involvement of the transmitter systems of the neostriatum in automation of motor skills in dogs.

Chronic experiments were performed on six dogs to address the influence of automation of a motor skill on the components of an operant defensive reflex, rearrangement of posture, and the characteristics of the projection of the center of mass on a tensometric platform by the forepaws; the effects of activation and blockade of muscarinic and dopamine receptors on the process of automation of the motor skill were also studied. Despite high criteria for execution of the operant reflex, the reproducibility of reflex performance, increases in the tonic component of the response, and the clear diagonal pattern of the postural rearrangement, a local (as opposed to diffuse) projection of the position of the center of mass on the tensometric platform by the forepaws was seen only after prolonged training leading to automation of the skill. The effect of automation of the operant response could be obtained immediately following bilateral microinjection of the muscarinic receptor agonist carbachol into the neostriatum. The same effect, but weaker, was obtained using bilateral microinjections of the dopamine D2 receptor blocker raclopride into the neostriatum. Conversely, bilateral microinjections of the selective muscarinic M1 receptor blocker pirenzepine into the neostriatum gave the opposite result, with increases in the phasic component of the response, impairment of the diagonal pattern of the postural rearrangement, and diffuseness of the projection of the center of mass on the tensometric platform by the forelimbs. It is concluded that the indirect efferent output of the neostriatum has an important role in the process of learning the motor operant reflex involving maintenance of a defined degree of flexion (where the main role is played by the tonic component of the movement) and during the process of automation of the motor skill.

Animals↗
PubMed1994

Cerebral hemidecortication alters expression of transforming growth factor alpha mRNA in the neostriatum of developing rats.

Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide which acts at the epidermal growth factor receptor to produce its biologic effects. Recent studies have demonstrated that TGF alpha may act as a neurotrophic factor. Cerebral hemispherectomy (hemidecortication) is performed on some children with intractable epilepsy. Prior studies have demonstrated improved functional recovery in both children and animals when the surgery is performed at a very early age. In order to test whether TGF alpha may be involved in the functional recovery of the neostriatum following cerebral hemidecortication, we performed in situ hybridization for TGF alpha mRNA on brains of rats which underwent hemispherectomy at postnatal day (P) 6 or P12 or in adulthood, and sacrificed one, 7, or 30 days following surgery. Normal striatal expression in control animals was very high at P6 and then decreased throughout development. In animals undergoing lesion at earlier ages (P6 and P12), TGF alpha mRNA expression was first depressed in the ipsilateral neostriatum one day after surgery and then elevated to supranormal levels 7 and 30 days after surgery. Maximal decreases (40% below contralateral neostriatum) were seen in animals lesioned at P12 and sacrificed the next day. Maximal elevations (60% greater than opposite neostriatum) were seen in animals operated on at P6 and sacrificed 30 days post surgery. Expression in the adult animal was only mildly affected, with a 20% increase found in the ipsilateral caudate 7 days after the lesion, but no significant changes after one or 30 days survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1996

Evidence for aspartate-immunoreactive neurons in the neostriatum of the rat: modulation by the mesencephalic dopamine pathway via D1-subtype of receptor.

Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D1-dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D1-dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80,000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D1-receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum.

Animals↗
PubMed1996

Synaptic transmission and modulation in the neostriatum.

The neostriatum is the entryway into the basal ganglia and is the site of many of the neurological defects involving basal ganglia function. Thus, it is important to understand the regulation of synaptic transmission at afferent synapses innervating the neostriatum. Cortical glutamatergic and nigral dopaminergic afferent input impinge on neurons in the neostriatum, providing the most significant afferent inputs to this structure. Our understanding of the mechanisms involved in transmission and modulation of transmission at these synapses has greatly increased. It is now apparent that the corticostriatal glutamatergic inputs produce rapid depolarization of striatal neurons via activation of ionotropic AMPA-type glutamate receptors. In addition, transmission is modulated by a number of presynaptic, G-protein-coupled receptors but, surprisingly, relatively little evidence of postsynaptic modulation has been observed. Corticostriatal synapses also express certain forms of plasticity, most notably short- and long- term synaptic depression (STI) and LTD, respectively). It appears that LTD may involve convergent actions of glutamate and dopamine. Striatal LTD may have important roles in information storage and motor set selection in the striatum. However, some aspects of synaptic transmission in the striatum remain unclear. In particular, the exact physiological roles of dopaminergic nigrostriatal input and the role of NMDA-type glutamate receptors are not well understood. In addition, intrastriatal synaptic connections have received relatively little attention as compared with extrinsic input to the neostriatum. Future studies will need to focus on elucidating these aspects of neostriatal function.

Animals↗
PubMed2001

Distribution of serotonin, its metabolites and 5-HT transporters in the neostriatum of Lurcher and weaver mutant mice.

Serotonin (5-HT) uptake sites, or transporters, were measured in the neostriatum (caudate putamen) of wild type (+/+) mice and heterozygous (wv/+) and homozygous (wv/wv) weaver, as well as in heterozygous Lurcher (Lc/+) mutants. These topological surveys were carried out by quantitative ligand binding autoradiography using the uptake site antagonist [3H]-citalopram as a probe of innervation densities in four quadrants of the rostral neostriatum and in two halves of the caudal neostriatum. In addition, tissue concentrations of 5-HT, 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol were measured by high-performance liquid chromatography with electrochemical detection in these neostriatal divisions. In +/+ mice and in Lc/+ mutants there was a dorso-ventral gradient of increasing 5-HT levels, and they exhibited a similar heterogeneity of [3H]-citalopram labeling. In contrast, the gradients of 5-HT concentrations and [3H]-citalopram binding disappeared in the weaver mutants, suggesting a rearrangement of the 5-HT innervation. This reorganization of the 5-HT system in the neostriatum was more obvious in the wv/wv and is compatible with the hypothesis that the postnatal dopaminergic deficiencies that characterize weaver mutants lead to a sprouting of fibers and thus constitute a genetic model of dopaminergic denervation that leads to a 5-HT hyperinnervation.

Animals↗
PubMed2003

Differential expression of N-methyl-D-aspartate receptor subunit messenger ribonucleic acids and immunoreactivity in the rat neostriatum during postnatal development.

The present study was performed to investigate the patterns of gene expression of N-methyl-D-aspartate (NMDA) receptors (NRs) in the rat neostriatum during postnatal development. Reverse transcriptase-polymerase chain reactions (RT-PCR) indicated that levels of NR1, NR2A and NR2D mRNAs reached peak levels between postnatal days 7 (PND 7) and PND 14. The levels of NR2B and NR2C mRNAs were low at PND 1 and their levels increased at PND 7 and remained high in adults. Immunofluorescence combined with image analysis revealed that the levels of NR1 immunoreactivity rose to its maximum at PND 14. In contrast, NR1 immunoreactivity rose progressively in perikarya of striatal neurons. Levels of NR2A immunoreactivity in the neostriatum were highest in adults. However, levels of NR2A immunoreactivity were higher in striatal neurons at PND 1 and PND 7. Levels of NR2B immunoreactivity were highest at PND 7. In the perikarya of striatal neurons however, the highest levels of NR2B immunoreactivity were detected at PND 14 and adult striatal neurons. In addition, double immunofluorescence revealed that the levels of NR1 immunoreactivity increased but the levels of NR2A immunoreactivity were the same in parvalbumin (PV)-positive striatal interneurons of PND 14 and adult rats. NR2B immunoreactivity was not detected in PV-positive neurons of PND 14 rats, but intense NR2B labeling was seen in PV-positive neurons of adult rats. Last but not least, in choline acetyltransferase (ChAT)-positive striatal interneurons of PND 14 and adult rats, levels of NR1 and NR2A immunoreactivity was seen to increase. Level of NR2B immunoreactivity remained the same in ChAT-positive neurons of PND 14 and adult rats. The present results indicate that there are differential patterns of expression of NR mRNAs and immunoreactivity in the neostriatum during different stages of postnatal development. Different combinations of NR have been found in different subpopulations of striatal neurons at different developmental stages. NR1, NR2A and NR2B are the major NMDA receptor subunits expressed during development. The change in patterns of expression of NR may be related to the functional maturation of neurons in the neostriatum.

Animals↗
PubMed2001

Identification of the source of the bilateral projection system from cortex to somatosensory neostriatum and an exploration of its physiological actions.

Microinjections of cholera toxin B subunit were made into the area of the neostriatum that receives input from the primary somatosensory barrel cortex (SI) in the rat. Studies of the cortices then allowed retrograde identification of the cortical cells supplying the striatal input. When injections were restricted to the neostriatum, retrograde labelling was found in layer V of both SI cortices. Ipsilateral to the injection, cells were retrogradely filled with toxin in all parts of the barrel field, in adjacent parietal cortex, in the motor cortex and in prefrontal areas. A similar distribution across cortical areas was seen contralaterally; however, the stained cells in the SI were between rather than within barrel columns. An earlier anterograde study suggested two inputs from the SI to the neostriatum. The present results indicate that one input to the somatosensory area of the neostriatum arises bilaterally from neurons between the barrels of the SI, while the topographic pathway from below the barrels is present only ipsilaterally. These anatomical results indicate that separate stimulation of the two corticostriatal pathways from the barrel cortex is possible. Electrical stimulation of the contralateral cortex will activate the bilateral pathway, while electrical stimulation of the whisker pads activates the barrels and hence the topographic pathway. Neurons in the somatosensory region of the striatum responded to stimuli in the contralateral cortex and in the contralateral whisker pad. In spite of very different path lengths, stimuli via the two routes gave rise to excitatory postsynaptic potentials in the striatal cells with similar latencies. The excitatory postsynaptic potentials to whisker pad stimulation had a rapid rise time and usually resulted in at least one action potential. Responses to stimulation of the contralateral cortex rose to a peak more slowly and were more variable in latency, but also gave rise to an action potential in the majority of cases. All the neurons had the physiological characteristics of medium-sized densely spiny cells and after intracellular filling with biocytin had the appropriate morphology. In summary, we propose that two corticostriatal pathways arise from layer V cells in the barrel area of the somatosensory cortex; one is bilateral and arises from cells mainly below the septa, while a topographical pathway arises from cells below the barrels. Both pathways can raise the spiny output cells of the striatum to firing threshold. The latencies from the contralateral cortex imply slowly conducting fibres with considerably more temporal dispersion than the pathway from below the barrels, which we excited from the contralateral periphery.

Animals↗
PubMed2001

GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: an in vivo study with stereology.

Amino-acid neurotransmitters regulate a wide variety of developmental processes in the mammalian CNS including neurogenesis, cell migration, and apoptosis. In order to investigate the role of GABA in early development of forebrain interneurons, we determined the survival of parvalbumin-immunoreactive GABAergic interneurons in the adult rat striatum following prenatal exposure to either GABA(A) receptor agonist or antagonist. Unbiased stereology was used to quantify parvalbumin-immunoreactive neuron number in the neostriatum of adult rats exposed to the drugs in utero, and the results were compared to pair-fed or vehicle controls. Embryos were exposed to the GABA(A) antagonist (bicuculline) or agonist (muscimol) during previously defined proliferative or post-proliferative periods for parvalbumin-immunoreactive interneurons. Unbiased stereology using the optical fractionator was used to estimate the total number of parvalbumin-immunoreactive neurons in neostriatum of experimental and control rats. No significant alteration in parvalbumin-immunoreactive neuron number was observed in rats treated with either bicuculline (1 or 2mg/kg/day) or muscimol (1mg/kg/day) during the proliferative phase. Administration of bicuculline during the post-proliferative phase significantly reduced parvalbumin-immunoreactive neuron number in the neostriatum. A concomitant decrease in neostriatal volume was also observed, suggesting that the effect is not restricted to parvalbumin-immunoreactive interneurons. Positional analysis revealed loss of normal regional distribution gradients for parvalbumin-immunoreactive neurons in neostriatum of rats exposed to bicuculline in the embryonic post-proliferative phase. This data collectively suggests that GABA promotes survival but not proliferation of parvalbumin-immunoreactive progenitors. GABA may also promote migration of subpopulations of interneurons that ultimately populate the ventral telencephalon.

Animals↗
PubMed1997

Synaptology of the nigrostriatal projection in relation to the compartmental organization of the neostriatum in the rat.

The patch-matrix organization of the striatal complex, which is fundamental to the structural and functional organization of the basal ganglia, is characterized on the basis of both connections and neurochemistry. In order to determine whether differences in the connections and neurochemistry are reflected in differences in synaptic organization, we examined the synaptology of the dopaminergic nigrostriatal projection in the patch-matrix complex of the rat. Three approaches were used. First, deposits of the anterograde tracer, biotinylated dextran amine, were placed in the substantia nigra. Sections of perfuse-fixed neostriatum were then processed to reveal anterogradely-labelled nigrostriatal axons and calbindin-D28k immunoreactivity, a marker for the patch-matrix complex. Secondly, sections of perfuse-fixed neostriatum were immunolabelled to reveal both tyrosine hydroxylase, a marker for dopaminergic structures and calbindin-D28k. Labelled axons in the patches and the matrix were examined at both the light and the electron microscopic levels. Finally, in order to test for the presence of fixed GABA in sub-type of anterogradely-labelled terminals in the neostriatum, ultrathin sections were immunolabelled by the post-embedding immunogold method. Based on morphological analysis, anterogradely-labelled nigrostriatal axons were divided into two types (Type I and Type II). The density of tyrosine hydroxylase labelling in the neostriatum prevented the classification of immunolabelled nigrostriatal axons. The Type I anterogradely-labelled axons and tyrosine hydroxylase-positive axons were found both in the patches and in the matrix. They both formed symmetrical synapses with spines, dendrites and occasionally somata. The morphology, dimensions, type of synaptic specialization and the distribution of postsynaptic targets of axons labelled by both methods were similar in the patches and the matrix. The Type I anterogradely-labelled axons were immunonegative for GABA. The Type II anterogradely-labelled axons were GABA-immunopositive, were found only in the matrix and were only present in those animals in which retrograde labelling was observed in the globus pallidus, they are thus not part of the dopaminergic nigrostriatal projection. It is concluded that although the patch-directed and matrix-directed dopaminergic projections from the ventral mesencephalon arise from different populations of dopaminergic neurons, their innervation of neurons in the patches and matrix is similar. The anatomical substrate, and therefore probably also the mechanism, for dopaminergic modulation of the flow of cortical information through the striatal complex in essentially the same in the patch and in the matrix sub-divisions of the striatal complex.

Animals↗