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PubMed2000

The cat neostriatum: relative distribution of cholinergic neurons versus serotonergic fibers.

The distribution of choline acetyltransferase (ChAT)-containing neurons and serotonin (5-HT)-containing nerve fibers in the cat neostriatum was investigated by use of immunohistochemical techniques. Both ChAT- and 5-HT-staining techniques were applied to alternate brain sections, thereby allowing a precise comparison of the distribution pattern of ChAT-immunopositive cells (ChAT cells) and 5-HT-immunopositive fibers (5-HT fibers). In the neostriatum, ChAT cells were strongly stained throughout their cell bodies and proximal (first-order) dendrites. The majority of them were multipolar cells with a soma diameter of 20-50 microm (long axis)x10-30 microm (short axis). In the caudate nucleus, ChAT cells were evenly and diffusely distributed except for the dorsolateral region of its rostral half, in which latter region they were distributed in loosely formed clusters. In the rostral portion of the putamen, the density of ChAT-cell distribution was like that in the medial region of the caudate nucleus. In contrast, this distribution was more dense in the caudomedial region of the putamen, adjacent to the globus pallidus. 5-HT fibers in the neostriatum were dark-stained, of quite fine diameter (<0.6 microm), and they contained small, round varicosities (diameter, usually 0.5-1.0 microm, but some >1.0 microm). Such 5-HT fibers were distributed abundantly throughout the caudate nucleus and putamen. In the rostrocaudal portion of the caudate nucleus, their density was high in its dorsal and ventral components, and low in the middle component. Throughout the putamen, 5-HT fibers were distributed homogeneously in the mediolateral and dorsoventral directions. In the caudal portion of the putamen adjacent to the globus pallidus, the 5-HT fibers had a higher density while maintaining their homogenous distribution pattern. In the two main divisions of the striatum, the so-called 'patch' (acetylcholinesterase (AChE)-poor) and 'matrix' (AChE-rich) compartments, there was a near-even distribution of 5-HT fibers and terminals. The above results suggest that the 5-HT-dominated, raphe-striatal pathway is optimally arranged for modulating the activity of both the intrinsic and the projection neurons of the neostriatum.

Acetylcholine↗
PubMed1998

p75NGFR mediates death of cholinergic neurons during postnatal development of the neostriatum in mice.

We have previously shown that p75 nerve growth factor receptor (p75NGFR) mediates apoptosis of approximately 25% of the cholinergic basal forebrain neurons in normal control mice between postnatal day 6 and 15, but only of cholinergic neurons that lacked the nerve growth factor receptor TrkA. Here, we investigated whether and when the cholinergic neurons of the neostriatum, which express TrkA and p75NGFR during early postnatal times, undergo p75NGFR-mediated death. The cholinergic neurons in the lateral neostriatal regions expressed choline acetyltransferase (ChAT) earlier (postnatal day 3-6) than those of the medial regions and TrkA appeared before ChAT in all regions. Between postnatal day 6 and 10, approximately 40% of the ChAT-positive neurons in the most lateral regions disappeared in control mice but not in p75NGFR-deficient mice. During this time, the neostriatum of control, but not p75NGFR-deficient, mice contained many apoptotic cells. This suggests that, similar to the cholinergic neurons of the basal forebrain, the neostriatal cholinergic neurons of control mice die and that this process is mediated by p75NGFR. However, the roles of p75NGFR and TrkA appear to be more complicated in the neostriatum where relatively few neurons express p75NGFR during the death phase (and predominantly in the lateral neostriatum where the neuronal loss is greatest), and TrkA-positive as well as TrkA-negative neurons may be lost.

Animals↗
PubMed2000

Immunolesioning of glutamate receptor GluR1-containing neurons in the rat neostriatum using a novel immunotoxin.

1. To investigate the potency of a novel immunotoxin that is specific for glutamate receptor GluR1, a subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type receptor channel, immunolesioning was performed. 2. A ribosome-inactivating protein, trichosanthin (TCS), was isolated and conjugated to the goat anti-rabbit IgG antibody molecule. The anti-rabbit antibody-TCS complex was preincubated with GluR1-specific rabbit antibody to produce a GluR1-specific immunotoxin. The immunotoxin was unilaterally administered into either the neostriatum or the lateral ventricle of rats. 3. Immunoreactivity for GluR1 or GluR4 was revealed in perfuse-fixed sections of the neostriatum obtained from the lesioned and control animals by immunocytochemistry. After ventricular or striatal injections of the immunotoxin, depletions of GluR1-immunoreactive neurons, the presumed GABAergic interneurons in the neostriatum, were found. Depletions of GluR4-immunoreactive perikarya, the presumed same subpopulation of striatal interneurons, were also found. In addition, no change in the pattern of distribution of immunoreactivity for GluR2 or glial fibrillary acidic protein was found in the lesioned neostriatum. These results indicate that the novel GluR1 immunotoxin is potent and specific. 4. In addition, striatal application of the immunotoxin caused a greater depletion in the number of GluR1-immunoreactive neurons. The present results also indicate that the route of immunotoxin application may be important in producing specific lesions.

Animals↗
PubMed2000

A new subdivision, marginal division, in the neostriatum of the monkey brain.

A new subdivision, the "marginal division" (MrD), was discovered at the caudal border of the striatum and surrounds the rostral edge of the globus pallidus in the rat brain in our previous studies. The neuronal somata of the MrD are mostly fusiform in shape with their long axes lining dorsoventrally. The MrD is more densely filled with substance P (SP)-, Leucine-enkephalin (L-Enk)-, dynorphin B-, neurotensin-, somatostatin- and cholecystokinin (CCK)-immunoreactive fibers and terminal-like structures than the rest of the striatum. The MrD was confirmed in the cat neostriatum as well. The present study intended to explore whether the MrD exists in the monkey neostriatum (putamen) with Nissl, histochemical and immunohistochemical methods. A band of fusiform neurons were obviously identified at the caudomedial edge of the putamen. These neurons lie outside the lateral medullary lamina and indirectly surround the rostrolateral border of the globus pallidus. The abundance of SP-, L-Enk-, neuropeptide Y-, CCK-, dopamine- and serotonin-positive fibers and terminal-like structures with a few positive fusiform neurons accumulating at the caudomedial border of the putamen obviously distinguishes this zone from the rest of neostriatum and globus pallidus. The acetylcholinesterase (AChE) positive and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) containing fusiform neurons are distinctly visualized in the same zone. The morphological figure and the location of these neurons, and the histochemical and immunohistochemical characteristics of this area coincide well with those of the MrD in the rat and cat striatum. This study thus convincingly identifies the existence of the MrD in the monkey neostriatum. It is fairly asserted that the MrD is a universal structure in the mammalian brain.

Animals↗
PubMed2004

Motor behavior in rats after separate and combined administration of GABAergic agents into the neostriatum.

Chronic experiments were performed on rats to study the main inhibitory transmitter system of the neostriatum--the GABAergic system--in the regulation of normal and pathological motor behavior. Studies addressed the effects of separate and combined administration of GABA (45 microg) and A-type receptor antagonists, i.e., picrotoxin (1 microg) and bicuculline (5 microg), into the neostriatum on the performance by rats of spontaneous (including pathological) and conditioned reflex motor behavior (active avoidance reflex in a shuttle box). Agents were injected in a volume of 1 microl daily for three weeks; control animals received physiological saline. Activation of the GABAergic system of the neostriatum had no significant effect on behavior. Conditioned reflex avoidance behavior was impaired throughout the period of bicuculline administration (there was no significant change in spontaneous behavior); this recovered after the course of microinjections finished. Picrotoxin produced smaller negative effects on performance of the reflex, though rats showed clear imperative movements in the form of choreomyoclonic hyperkinesia. Simultaneous administration of picrotoxin and GABA into the neostriatum produced less hyperkinesia; administration of picrotoxin and bicuculline altered the nature of hyperkinesia. The importance of the GABAergic system for the antihyperkinetic activity of the basal ganglia is discussed, and it is suggested that the GABA-A subsystem is of critical importance in these functions.

Animals↗
PubMed1994

The effect of kainic acid on the release of GABA in rat neostriatum and substantia nigra.

In order to test the hypotheses that stimulation of non-N-methyl-D-aspartate (NMDA) receptors in the neostriatum causes the release of gamma-aminobutyric acid (GABA) from nigrostriatal neurones, dual microdialysis was carried out in the neostriatum and substantia nigra of freely moving rats. Application of kainic acid to the neostriatum caused a dose-dependent release of GABA both locally and, at the same time, from the ipsilateral substantia nigra. These effects were blocked by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Direct application of kainic acid to the substantia nigra caused a DNQX-sensitive local release of GABA. It is concluded that excitatory amino acid receptor stimulation of the neostriatum releases GABA from striatonigral neurones and that stimulation of the substantia nigra causes the release from striatonigral terminals and/or the collaterals of nigrofugal neurones.

Animals↗
PubMed1996

Synaptic connections between spiny neurons of the direct and indirect pathways in the neostriatum of the rat: evidence from dopamine receptor and neuropeptide immunostaining.

UNLABELLED: The flow of cortical information through the basal ganglia occurs through the so-called 'direct pathway' and 'indirect pathways'. The object of the present work was to attempt to determine whether spiny neurons in the neostriatum that give rise to the direct pathway (i.e. the striatonigral/entopeduncular pathway) and those giving rise to the indirect pathways (i.e. striatopallidal pathway) are synaptically interconnected. The approach was to carry out double immunocytochemistry at the electron microscopic level using antibodies against peptides or dopamine receptor subtypes that are selectively associated with the neurons that give rise to the direct (substance P or D1 receptors) and indirect pathways (enkephalin or D2 receptors). Sections of perfuse-fixed rat neostriatum were immunostained to reveal both substance P immunoreactivity and D2 receptor immunoreactivity or enkephalin and D1 receptor immunoreactivity, respectively. Double peroxidase methods were employed using different chromogens that were distinguishable at both the light and electron microscopic levels. In the electron microscope substance P-immunoreactive terminals were seen in synaptic contact with dendritic structures that displayed immunoreactivity for D2 receptor. Similarly, enkephalin-immunoreactive terminals were seen in synaptic contact with D1-immunoreactive dendritic structures. Thus, axon collaterals of neurons giving rise to the direct pathway form synaptic contacts with neurons that give rise to the indirect pathway and axon collaterals of neurons giving rise to the indirect pathway form synaptic contact with neurons that give rise to the direct pathway. These results indicate that the two pathways of information flow through the basal ganglia are synaptically linked at the level of the neostriatum. KEYWORDS: spiny neurons, direct pathway,indirect pathways, rat neostriatum

Animals↗
PubMed1997

Role of the dorso-caudal neostriatum in filial imprinting of the domestic chick: a pharmacological and autoradiographical approach focused on the involvement of NMDA-receptors.

Newly hatched domestic chicks were either acoustically imprinted on 400 Hz tone pulses or visually imprinted on a rotating red light. Compared to naive control animals, both groups of imprinted chicks expressed significantly enhanced stimulus evoked 2-fluoro-2-deoxyglucose (2-FDG) uptake in circumscribed areas of the dorso-caudal neostriatum (Ndc). This enhanced excitability after imprinting seems not to be related to changes of NMDA-receptor densities as measured by quantitative receptor autoradiography. However, pharmacological blockade of NMDA-receptors in the dorso-caudal neostriatum leads to a marked suppression of stimulus-evoked 2-FDG uptake in the dorso-caudal neostriatum and also in the interconnected imprinting relevant forebrain area, medio-rostral neostriatum/hyperstriatum ventrale (MNH). Furthermore, chicks which received bilateral Ndc injections of the competitive NMDA antagonist DL-2-amino-5-phosphono valeric acid (APV) during the imprinting experiments showed a dose-dependent decrease of imprinting success compared to vehicle-injected controls. These results indicate that the dorso-caudal neostriatum may represent a polysensory associative brain region in which visual and acoustic features of imprinting objects may be integrated. The activation in this area evoked by the imprinting stimulus during and after imprinting is critically dependent on NMDA-receptor activation, which appears to be required for this learning process.

2-Amino-5-phosphonovalerate↗
PubMed1976

Cyclic nucleotide phosphodiesterase in rat neostriatum: properties of the enzyme in crude homogenates.

Homogenates of rat neostriatum hydrolysed cGMP faster than cAMP at both high (100 microM) and low (1 microM) substrate concentrations, although the hydrolysis of both nucleotides exhibited similar kinetic properties. Kinetic analysis of the effect of substrate concentration on the rate of cAMP and cGMP hydrolysis gave results characteristic of a negatively cooperative enzyme species, with two apparent Km's for each nucleotide. The ratio between the Vmax of the high Km form and the Vmax of the low Km form was similar in various subcellular fractions of neostriatal tissue, in a preparation of synaptic membranes from whole brain, and in homogenates of other brain regions, including both neural-rich and glial-rich tissues. In homogenates of neostriatum cAMP could almost completely block cGMP hydrolysis and vice versa. The kinetics of this inhibition were competitive at low (1 microM) substrate concentrations, and non-competitive at high (100 microM) substrate concentrations. Various phosphodiesterase inhibitors failed to preferentially inhibit the hydrolysis of either nucleotide at high or low nucleotide concentrations. Preliminary studies of the effect of a Ca(2+)-dependent endogenous activator preparation on the hydrolysis of cyclic nucleotides in homogenates of rat neostriatum showed a specific activation of cGMP hydrolysis at low nucleotide concentrations. The rate of cGMP hydrolysis at 1 microM substrate concentration was doubled in the presence of the activator preparation and 100 microM-CaCl2, while cGMP hydrolysis at 100 microM or cAMP hydrolysis at both 1 microM and 100 microM remained unaffected. These observations raise the possibility that cAMP and cGMP may be hydrolysed by the same enzyme in rat neostriatum, and that an endogenous activating factor may determine the relative affinities of the enzyme for the two nucleotides.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Cyclic nucleotide phosphodiesterase in rat neostriatum: multiple isoelectric forms with similar kinetic properties.

Separation of multiple forms of cyclic nucleotide phosphodiesterase from the soluble supernatant fraction of rat neostriatum by isoelectric focusing yielded five separate peaks of cyclic nucleotide hydrolysing activity. Each separated enzyme form displayed a complex kinetic pattern for the hydrolysis of both cyclic AMP and cyclic GMP, and there were two apparent Km's for each nucleotide. At 1 microM substrate concentration, four enzyme forms exhibited higher activity with cyclic AMP than with cyclic GMP, while one form yielded higher activity with cyclic GMP than with cyclic AMP. Cyclic AMP and cyclic GMP were both capable of almost complete inhibition of the hydrolysis of the other nucleotide in all the peaks separated by isoelectric focusing; the IC50's for this interaction correlated well with the relative rates of hydrolysis of each nucleotide in each peak. The ratio of activity at 1 microM substrate concentration for the five enzyme forms separated by isoelectric focusing was 10:10:5:15:1 for cyclic AMP hydrolysis; and 6:6:4:8:2 for cyclic GMP hydrolysis; and the isoelectric points of the five peaks were 4.3, 4.45, 4.7, 4.85, and 5.5, respectively. Known phosphodiesterase inhibitors did not preferentially inhibit any of the separated forms of activity for either cyclic AMP or cyclic GMP hydrolysis, at either high (100 microM) or low (1 microM) substrate concentrations. Preliminary examination of the subcellular distribution of the different forms of enzyme activity indicated a different degree of attachment of the various forms to particulate tissue components. Isoelectric focusing of the soluble supernatant of rat cerebellum gave rise to a slightly different pattern of isoelectric forms from the neostriatum, indicating a different cellular distribution of the isoelectric forms of PDE in rat brain. Polyacrylamide disc gel electrophoresis of the soluble supernatant of rat neostriatum also generated a characteristic pattern of five separate peaks of cyclic nucleotide phosphodiesterase activity, each of which hydrolysed both cyclic AMP and cyclic GMP. Polyacrylamide gel electrophoresis of single enzyme forms previously separated by isoelectric focusing gave single peaks, with a marked correspondence between the enzyme forms produced by isoelectric focusing and those produced by gel electrophoresis, suggesting that both protein separation procedures were isolating the same enzyme forms. The results indicate the existence of multiple isoelectric forms of cyclic nucleotide phosphodiesterase in the soluble supernatant fraction of rat neostriatum, all of which exhibit similar properties. In this tissue a single kinetic form of this enzyme appears to exist displaying complex kinetic behaviour indicative of negative cooperativity and hydrolysing both cyclic AMP and cyclic GMP, with varying affinities.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain.

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h with little or no ODN remaining in the neostriatum after 48 h. In comparison, fluorescently-labelled ODNs delivered using polymer microspheres were intensely visible in cells after 48 h post-administration and the fluorescence appeared to be diffuse covering both cytosolic and nuclear regions. Dual-label immunohistochemical analyses suggested that ODNs were mainly distributed to neuronal cells. These data indicate that site-specific administration of ODNs using biodegradable polymer microspheres will not only provide sustained delivery of nucleic acids but can also improve the cellular distribution of ODNs to brain cells. Sustained or controlled-release biodegradable polymer formulations, therefore, represent an attractive strategy for improved local delivery of ODNs to the CNS.

Animals↗
PubMed1978

Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum.

In this study the location of dopamine (DA) neuron perikarya in the rostral mesencephalon of the rat was determined using the glyoxylic acid fluorescence histochemical technique. Subsequently the topography of the projection of these mesencephalic neurons on the basal forebrain and striatum was analyzed using the anterograde transport-autoradiographic tracing method and the retrograde transport-horseradish peroxidase (HRP) technique. The results of these anatomical studies were correlated with the biochemical and histochemical studies presented in previous reports (Moore, '78; Fallon and Moore, '78; Fallon et al., '78) to provide the following conclusions. The topography of the DA neuron projection of the basal forebrain and neostriatum is organized in three planes, dorsal-ventral, medial-lateral and anterior-posterior. DA cells are found almost exclusively in the substantia nigra (SN) and ventral tegmental area (VTA). Ventral cells of the SN and VTA project to the dorsal structures of the basal forebrain such as the septum, nucleus accumbens and neostriatum. The latter includes some DA cells located ventrally in the pars reticulata of the SN. Dorsal cells project to ventral structures. The medial-lateral topography is organized such that the medial sectors of the SN-VTA area project to the medial parts of nuclei in the basal forebrain and neostriatum whereas lateral sectors of the SN-VTA area project to the lateral parts of nuclei in the basal forebrain and neostriatum. An anterior-posterior topography also is evident such that anterior parts of the SN-VTA project anteriorly whereas the posterior SN-VTA projects more posteriorly in these areas. These observations are consistent with the view that the DA neurons of the SN-VTA complex form a single nuclear group with a highly topographically organized projection innervating not only deep nuclei of the telencephalon but allocortical structures as well.

Amygdala↗
PubMed1983

Fine structural studies on a type of somatostatin-immunoreactive neuron and its synaptic connections in the rat neostriatum: a correlated light and electron microscopic study.

Somatostatin-immunoreactive neurons in the rat neostriatum were studied by correlated light and electron microscopy using the peroxidase-antiperoxidase immunocytochemical technique. Immunoreactivity was localized in neuronal perikarya and processes. The perikarya were of spindle or fusiform shape (average length 16.9 microns) and were found in all parts of the neostriatum. From each neuron there arose two to four straight immunoreactive dendritelike processes, which could frequently be traced as far as about 130 microns from their perikaryon. Immunoreactive varicose axonlike processes were occasionally found, some of which were proximal axons of identified immunoreactive cells. Nine of the light microscopically identified neurons showing somatostatin-immunoreactivity were studied in the electron microscope; two of them had proximal axons with varicosities. Each neuron had an oval or elongated nucleus, which was always indented. These morphological features correspond well to those of certain "medium-size aspiny" neurons classified by Golgi studies. Although the immunoreactive endproduct was diffusely located throughout the neuron, it was characteristically located in the saccules and large granules (diameter 133 nm) of the Golgi apparatus, and large immunoreactive vesicles of similar size to those in the Golgi apparatus frequently occurred in all parts of axon. Very little synaptic input was found on the perikarya and dendrites of somatostatin-immunoreactive neurons. The perikarya and proximal dendrites received both symmetrical and asymmetrical synaptic input, while the distal dendrites usually received boutons that formed asymmetrical contacts. The somatostatin-immunoreactive boutons contained pleomorphic electron-lucent vesicles (diameter 39.3 nm) and a few large immunoreactive granular vesicles; these boutons always formed symmetrical synapses. Their postsynaptic targets were dendritic shafts, spines, and unclassified dendritic profiles. On the other hand, the varicosities of identified proximal axons of somatostatin-positive neurons did not form typical synapses, since they lacked clusters of small vesicles, but some of them were in direct apposition (via membrane specializations) to unlabelled perikarya or dendrites. It is concluded that somatostatin is a useful marker for a particular type of neuron in the neostriatum. The presence of somatostatin immunoreactivity in synaptic boutons is consistent with the view that somatostatin could be a neurotransmitter in the neostriatum.

Animals↗
PubMed1989

Dye-coupling in the neostriatum of the rat: I. Modulation by dopamine-depleting lesions.

Evidence from experiments performed in turtle and fish retina suggests that dopamine (DA) modulates the permeability of gap junctions. The present experiment was aimed at determining if DA has a similar role in the mammalian neostriatum. Adults rats received one of four treatments: unilateral electrolytic substantia nigra lesions, unilateral injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra, unilateral neocortical aspiration, or no treatment. After 3-5 weeks, neostriata from both sides of the brain were prepared for in vitro intracellular recordings. Recorded neurons (N approximately 150) were filled with Lucifer Yellow (LY), a low molecular weight dye that crosses gap junctions. In animals with electrolytic nigral lesions, dye-coupling in the ipsilateral neostriatum occurred after 38% of the intracellular injections. After 6-OHDA lesions, 19% of the injections produced dye-coupling in the ipsilateral neostriatum. This difference may have been accounted for by the fact that electrolytic lesions produced a greater degree of DA loss than 6-OHDA injections. Both of these percentages contrast with the very small percentage of dye-coupling found in intact animals or in animals with neocortical lesions. Dye-coupling occurred only between medium-sized spiny cells. No morphological differences between dye-coupled and non-dye-coupled cells were observed with light microscopy. Overall, passive and active electrophysiological properties of dye-coupled and single neurons were similar. The results suggest that DA may function in the neostriatum to control permeability of gap junctions.

Action Potentials↗
PubMed1984

Characterization of pallidonigral neurons in the rat by a combination of Golgi impregnation and retrograde transport of horseradish peroxidase: their monosynaptic input from the neostriatum.

After injection of horseradish peroxidase, or its conjugate with wheatgerm agglutinin, into the substantia nigra of rats, retrogradely labelled cells were found in the globus pallidus. Forty-six of these neurons were also impregnated by the Golgi procedure and then gold-toned: their somata ranged from 15 to 30 microns in diameter and these pallidonigral neurons had from two to five primary dendrites that were long and smooth, that branched infrequently and that bore occasional spines on their distal regions. Most of the neurons studied came from the lateral part of the globus pallidus. At the ultrastructural level, the identified pallidonigral neurons were found to have deeply infolded nuclei and an abundant cytoplasm; their perikarya were richly innervated by two distinct types of bouton, both of which formed symmetrical synaptic contacts. The dendrites of pallidonigral neurons were ensheathed in boutons, the majority forming symmetrical synaptic contacts. After placement of electrolytic lesions in the rostro-dorsal neostriatum, degenerating boutons were found in symmetrical synaptic contact with the cell bodies and dendrites of six identified pallidonigral neurons. It is concluded that pallidonigral neurons belong to the Golgi category of large pallidal neurons with smooth dendrites and that they receive monosynaptic input from the neostriatum. Thus, in addition to the direct striatonigral pathway, the neostriatum can influence the substantia nigra by a monosynaptic relay through the globus pallidus, which might allow other pallidal afferents to influence the transfer of information from neostriatum to substantia nigra.

Animals↗
PubMed1984

Activity of nigral dopaminergic neurons after lesion of the neostriatum in rats.

As shown by post-mortem analysis the major neuropathological trait of Huntington's chorea is a degeneration of the intrinsic neurons of the neostriatum (caudate nucleus and putamen). Such a situation can be reproduced by a destruction of the neostriatum by kainic acid. When injected into the caudate nucleus this excitatory amino acid destroys the intrinsic neurons of the neostriatum and spares fairly well the passing fibers. In the present work, we have chosen to examine the influence of neostriatal destruction on the activity of identified dopaminergic cells in the pars compacta of the substantia nigra. As a key element in the nigro-neostriato-nigral loop, this structure is a relevant site for observing the functional effects of neostriatal lesion. Our research hypothesis was based on the generally accepted view that the suppression of the important neostriato-nigral pathway and in particular the inhibitory GABAergic contingent, could generate a hyperactivity of nigral dopaminergic cells. One may therefore consider that the dopaminergic hyperactivity produces abnormal messages which can influence via several pathways the motoneurons, and which participates in the genesis of the hyperkinetic movements characteristic of chorea. After destruction of the neostriatum, we have shown that the pattern of discharge of most identified nigral dopaminergic neurons becomes greatly disorganized. This drastic change in the pattern of activity cannot be interpreted as the simple 'lift of a brake' on these cells by the suppression of the inhibitory GABAergic striato-nigral tract.

Animals↗
PubMed1985

Antidromic activation of dorsal raphe neurons from neostriatum: physiological characterization and effects of terminal autoreceptor activation.

Three types of neurons, distinguished on the basis of their spontaneous firing rates and patterns, extracellularly recorded waveforms and responses to neostriatal stimulation, were observed in the dorsal raphe nucleus in urethane-anesthetized rats. Type 1 neurons (presumed to be serotonergic) fired spontaneously from 0.1 to 3 spikes/s in a regular pattern, with initial positive-going bi- or triphasic action potentials. Type 1 cells exhibited long-latency antidromic responses to neostriatal stimulation (mean +/- S.E.M. 24.9 +/- 0.3 ms) that sometimes occurred at discrete multiple latencies, and supernormal periods persisting up to 100 ms following spontaneous spikes. Type 2 cells fired spontaneously in an irregular, somewhat bursty pattern from 0 to 2 spikes/s with initial negative-going biphasic spikes, and were antidromically activated from neostriatal stimulation at shorter latencies than Type 1 cells (21.8 +/- 0.9 ms). Type 3 cells were characterized by initial positive-going biphasic waveforms and displayed a higher discharge rate (5-30 spikes/s) than Type 1 or Type 2 cells. Type 3 cells could not be antidromically activated from neostriatal stimulation. The relatively long conduction time to neostriatum of the Type 1 presumed serotonergic neuron is discussed with respect to previous interpretations of the synaptic action of serotonin in the neostriatum. In conjunction with these antidromic activation studies, the neurophysiological consequences of serotonergic terminal autoreceptor activation were examined by measuring changes in the excitability of serotonergic terminal fields in the neostriatum following administration of the serotonin autoreceptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The excitability of serotonergic terminal fields was decreased by intravenous injection of 40 micrograms/kg 5-MeODMT, and by infusion of 10-50 microM 5-MeODMT directly into the neostriatum. These results are interpreted from the perspective of mechanisms underlying autoreceptor-mediated regulation of serotonin release.

Animals↗
PubMed1987

Serotonin innervation in adult rat neostriatum. I. Quantified regional distribution.

The distributional features of the serotonin (5-HT) innervation in adult rat neostriatum were examined and quantified using two complementary chemoanatomical methods: 5-HT-immunohistochemistry on serial histological sections and radioautography after [3H]5-HT uptake in whole cerebral hemisphere slices. As visualized and measured after peroxidase-antiperoxidase immunostaining, the neostriatal 5-HT fiber network pervading the entire neostriatum was 2-3 times denser in its ventral than dorsal parts, and showed a slight rostrocaudal increase in density. Its axonal length ranged from 1.06 to 4.18 m per mm3 of striatal tissue. Radioautographic counts of the [3H]5-HT-labeled axon varicosities within comparable sectors of the neostriatum showed good correlation with this distribution pattern. As extrapolated after appropriate corrections for incomplete detection at the chosen exposure time and from the thickness of sections examined, the number of neostriatal 5-HT varicosities (innervation density) ranged from 1.5 to 4.8 millions and averaged 2.6 millions per mm3 of tissue. These quantitative results provided new insights into the topographical organization of the dorsal raphe-neostriatal 5-HT projection system. They already allow for meaningful correlations with currently available microchemical data on intrastriatal 5-HT levels and should also be of considerable significance when as precise information becomes available on the number and localization of different 5-HT receptors and uptake carriers within rat neostriatum.

Animals↗