The localization of acetylcholinesterase in the corpus striatum and substantia nigra of the rat following kainic acid lesion of the corpus striatum: a biochemical and histochemical study.

The distribution of acetylcholinesterase in the corpus striatum and substantia nigra was examined with the use of kainic acid lesions of the corpus striatum and pharmacohistochemical experiments. Histochemically identified acetylcholinesterase-containing neurons in the striatum were among those which were destroyed by kainic acid. Complementary biochemical studies demonstrated that approximately 50% of the total acetylcholinesterase activity in the striatum was localized in these acetylcholinesterase-containing neurons. Intrastriatal injections of kainic acid produced a substantial decrease in the activity of the glutamic acid decar?ylase in the substantia nigra, thus demonstrating that neurons contributing to the striato- and/or pallidonigral pathways had been lesioned. However, nigral acetylcholinesterase activity was not significantly reduced by the striatal kainic acid injections. Furthermore, stereotaxic injections of colchicine along the course of the striatonigral projection failed to produce an accumulation of acetylcholinesterase in these fibers proximal to the injection. In contrast, injections of colchicine into the nigrostriatal projection led to a proximal accumulation of acetylcholinesterase in the fibers of this system, thus confirming the presence of acetylcholinesterase in the ascending dopaminergic neurons.It is concluded that the striato- and pallidonigral projections in the rat do not contain significant levels of acetylcholinesterase. Furthermore, acetylcholinesterase-containing neurons in the striatum appear to be interneurons rather than the source of striatal efferents. It is suggested that some of these acetylcholinesterase-containing neurons may be striatal cholinergic interneurons.     

Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis--II. Sensorimotor and learning impairments

The cholinergic projection from the nucleus basalis magnocellularis to the neocortex has been implicated in normal memory function and in the dementia of Alzheimer's disease. In order to investigate functions of this cholinergic system of the forebrain, rats with unilateral ibotenic acid lesions of the nucleus basalis magnocellularis have been compared with normal animals and with rats given cortically-placed transplants, either of cholinergic-rich embryonic ventral forebrain cells or of control noncholinergic cells taken from embryonic hippocampus. In the first experiment, lesions of the nucleus basalis magnocellularis led to impairments in step-through passive avoidance and Morris' water-maze tasks, and to locomotor hyperactivity attributable to a reduction in within-trial habituation. The ventral forebrain grafts, but not the noncholinergic hippocampal grafts, significantly ameliorated the deficits of passive avoidance retention, and of water-maze spatial accuracy, but had no effect on the acquisition impairments in either task, nor on the habituation deficit in locomotor activity of the nucleus basalis magnocellularis lesioned rats. In the second experiment, the lesions induced contralateral sensory neglect and ipsilateral turning biases, which were also partially ameliorated by the ventral forebrain grafts. The results support the hypothesis that the basal forebrain-neocortical cholinergic system contributes to certain memory processes, but suggest a more general role for this system in other cortical functions also.     

Regional decreases of cortical choline acetyltransferase after lesions of the septal area and in the area of nucleus basalis magnocellularis

Choline acetyltransferase and [³H]choline uptake have been measured in neocortical regions and hippocampus one week after lesions which destroyed the septum bilaterally, and after unilateral lesions in the area of nucleus basalis magnocellularis. Lesions of the septal area, which severely decreased choline acetyltransferase in hippocampus, only moderately decreased choline acetyltransferase in a posterior cortical region and had no effect in frontal and parietal regions. In contrast, lesions which included nucleus basalis magnocellularis decreased choline acetyltransferase markedly in frontal and parietal regions and had less of an effect in the posterior cortical regions. Lesion-induced decreases of [³H]choline uptake paralleled those of choline acetyltransferase. Lesions which included nucleus basalis magnocellularis had no effect on choline acetyltransferase in hippocampus, nucleus accumbens, olfactory tubercle, midbrain or pons-medulla.These results suggest the existence of topographically distinct cholinergic inputs to neocortex. In agreement with previous studies, cholinergic projections from the peripallidal region of nucleus basalis magnocellularis are predominantly to frontal and parietal neocortex. In contrast to previous suggestions, cholinergic projections to neocortex from the septal area are limited to the posterior regions of neocortex.     

Transplantation of embryonic ventral forebrain neurons to the neocortex of rats with lesions of nucleus basalis magnocellularis--I. Biochemical and anatomical observations

Unilateral ibotenic acid lesions of the rat nucleus basalis magnocellularis produce approximately 60% depletion of choline acetyltransferase activity in ipsilateral frontal and frontoparietal neocortex. This depletion, which represents the loss of most of the extrinsic neocortical cholinergic input, is stable for at least 6 months. Embryonic ventral forebrain neurons survive transplantation to such cholinergically denervated neocortex. Cholinergic cells abound within these transplants and appear able to reinnervate the cholinergically depleted host cortex, as assessed histochemically and by measurement of choline acetyltransferase activity. Outgrowing fibres may extend beyond 2 mm from the grafts and often appear to be organized in an appropriate laminar pattern within the host cortex. Peptidergic neurons are sparse within the grafts and their fibres frequently appear unable to grow into the host tissue. Control grafts of non-cholinergic embryonic hippocampal cells survive well but have no effect on cortical depletions of acetylcholinesterase or choline acetyltransferase activity. Reconstruction of the extrinsic cholinergic input to the cortex by transplantation provides a useful tool for understanding the functions of this pathway.     

The effects of surgical and chemical lesions on neurotransmitter candidates in the nucleus accumbens of the rat.

The origin of fibers containing different neurotransmitter candidates in the nucleus accumbens of rat brain has been studied with surgical and chemical lesion techniques. Destruction of the medial forebrain bundle decreased the activity of aromatic amino acid decar?ylase by 80% in the nucleus. Cutting of the fornix or a hemitransection decreased the high affinity uptake of glutamate by 45% and the endogenous level of glutamate by 33%. The high affinity uptake of glutamate was concentrated in the synaptosomal fraction and the decrease after the lesion was most pronounced in this fraction. Restricted lesions indicated that fibers in the fimbria/fornix coming from the subiculum were responsible for this part of the glutamate uptake in the nucleus. Local injection of kainic acid into the nucleus was accompanied by a 75% decrease in choline acetyltransferase and a 35% decrease in acetylcholinesterase activities, a 70% decrease in glutamate decar?ylase activity and a 60% decrease in the high affinity uptake of γ-aminobutyrate, a 45% decrease in high affinity glutamate uptake, and no change in aromatic amino acid decar?ylase activity. Performing a lesion of the fornix after kainic acid injection led to an 85% decrease in high affinity glutamate uptake, without further affecting the other neuronal markers.The results indicate that all aminergic fibers to the nucleus accumbens are ascending in the medial forebrain bundle, that the subiculum—accumbens fibers are ‘glutamergic’, and that the nucleus also contains intrinsic glutamergic or aspartergic cells. Cholinergic and γ-aminobutyrate-containing cells are wholly intrinsic to the nucleus.     

Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine

The role of the cholinergic nucleus basalis magnocellularis in spatial learning and memory was studied in the rat. Animals received bilateral injections of ibotenic acid (5 micrograms/microliters) into the region of the nucleus basalis magnocellularis. Six weeks postoperatively they were deprived of food and trained for 5 weeks in a 16-arm radial maze in which 9 of the arms were baited with food. The nucleus basalis magnocellularis-lesioned animals showed significant deficits in the acquisition of the task. Further analysis of the data indicated that this was due primarily to a deficit in reference (long-term) as opposed to working (short-term) memory. After the 5-week training period the nucleus basalis magnocellularis-lesioned animals received intraperitoneal injections of physostigmine sulphate (0.5 mg/kg) 30 min before each daily trial for 1 week. This treatment resulted in a significant improvement in the performance of the spatial memory task on all three measures. The ibotenate lesions reduced the activity of choline acetyltransferase by about 40% in the anterior cortex and by 15% in the posterior cortex. Hippocampal choline acetyltransferase activity was not affected, indicating that the septohippocampal cholinergic projection was spared by the lesions. The activity of glutamate decarboxylase was not affected in any of these regions. These results suggest that the cholinergic projections of the nucleus basalis magnocellularis play an important role in the acquisition of a spatial memory task.     

Monkey nucleus basalis is enriched with choline acetyltransferase

The nucleus basalis of Meynert, which projects directly and diffusely to the cerebral cortex, was histologically identified in Nissl- and acetylcholinesterase-stained sections of the forebrain of Rhesus monkeys. Adjacent 1 mm thick sections were microdissected in 2 mm² blocks and assayed for choline acetyltransferase activity. The results demonstrate a marked enrichment of choline acetyltransferase activity in samples containing the nucleus basalis of Meynert and strongly suggest that this nucleus is a cholinergic nucleus in the primate.     

Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain

The effects of ablation of frontal, occipital or entire hemicortex on several neurotransmitter parameters in the rostral and caudal neostriatum, thalamus and the contralateral anterior medial cortex were investigated. In particular the effects on the high affinity uptake ofd-aspartate and on the endogenous level of amino acids, especially glutamate and aspartate, were studied in order to identify glutamate- or aspartate-containing nerve terminals in these regions.The results show a specific decrease in high affinity uptake ofd-aspartate in both rostral and caudal neostriatum ipsilateral to the lesion after frontal or entire hemidecortication. There was also a small but significant decrease ind-aspartate uptake on the contralateral side. Only the level of endogenous glutamate decreased in the neostriatum after hemidecortication. There was a specific decrease ind-aspartate uptake in the thalamus only ipsilateral to the cortical lesions. In thalamus there was a significant decrease both in the level of glutamate and to a smaller extent in that of aspartate after hemidecortication. Anterior medial cortex showed a very active high affinity uptake ofd-aspartate, which was slightly reduced after removal of the contralateral hemicortex. The high affinity uptake ofd-aspartate was in all cases mainly due to uptake in synaptosomes.The results show that the neostriatum receives glutamate-containing fibres from the neocortex, particularly the frontal part. This projection is mainly ipsilateral with a small element derived from the contralateral side. The thalamus, both the rostral and caudal parts, receives glutamate-containing fibres from the whole extent of the ipsilateral neocortex. Some of the corticothalamic fibres may also contain aspartate. The anterior medial cortex probably contains a high proportion of glutamate- and/or aspartate-containing nerve terminals but only a low proportion of these are derived from the contralateral cortex.     

Divergent effects of acute and chronic monosodium l-glutamate treatment on the anterior and posterior parts of the arcuate nucleus

Young albino rats were injected with either single or repeated doses of 0.1–6.0 mg/g body weight of monosodium l-glutamate between the ages of 2 and 40 days. The smallest, single effective dose was 0.25 mg/g body weight administered during the first week of life. The sensitivity to monosodium l-glutamate decreased with age. Monosodium l-glutamate caused nuclear pyknosis and edematous swelling of neurons in the anterior part of the arcuate nucleus which is located at the level of the ventromedial nucleus. These effects resulted in a reduction of neurons in this region. All of the doses used were ineffective in producing necrosis or cell death in the posterior part of the arcuate nucleus which is found at the level of the premamillary nuclei. The number of neurons in the arcuate nucleus of control animals was 46,500 with a neuron/glia ratio of 1.22. The anterior part of the arcuate nuclus had 55% of the neurons.Adult animals with an 80–90% loss of neurons in the anterior part of arcuate nucleus showed marked adiposity, hypoactivity, decreased body length, tail automutilation and reduced endocrine organ weight. The histological appearance of the ovaries, testes and pituitary glands was normal. The sexual behavior of these rats was normal, but the females were not fertile.The results of this study indicate that monosodium l-glutamate has a regional effect on the arcuate nucleus. These data also indicate that the majority of the neurons in the anterior arcuate region do not play a definitive role in the basal regulation of gonadotrophic hormones.     

Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6)

Monoclonal antibodies to choline acetyltransferase and a histochemical method for the concurrent demonstration of acetylcholinesterase and horseradish peroxidase were used to investigate the organization of ascending cholinergic pathways in the central nervous system of the rat. The cortical mantle, the amygdaloid complex, the hippocampal formation, the olfactory bulb and the thalamic nuclei receive their cholinergic innervation principally, from cholinergic projection neurons of the basal forebrain and upper brainstem. On the basis of connectivity patterns, we subdivided these cholinergic neurons into six major sectors. The Chl and Ch2 sectors are contained within the medial septal nucleus and the vertical limb nucleus of the diagonal band, respectively. They provide the major cholinergic projections of the hippocampus. The Ch3 sector is contained mostly within the lateral portion of the horizontal limb nucleus of the diagonal band and provides the major cholinergic innervation to the olfactory bulb. The Ch4 sector includes cholinergic neurons in the nucleus basalis, and also within parts of the diagonal band nuclei. Neurons of the Ch4 sector provide the major cholinergic innervation of the cortical mantle and the amygdala. The Ch5–Ch6 sectors are contained mostly within the pedunculopontine nucleus of the pontomesencephalic reticular formation (Ch5) and within the laterodorsal tegmental gray of the periventricular area (Ch6). These sectors provide the major cholinergic innervation of the thalamus. The Ch5–Ch6 neurons also provide a minor component of the corticopetal cholinergic innervation.

These central cholinergic pathways have been implicated in a variety of behaviors and especially in memory function. It appears that the age-related changes of memory function as well as some of the behavioral disturbances seen in the dementia of Alzheimer's Disease may be related to pathological alterations along central cholinergic pathways.     

Cortical projections of the nucleus of the diagonal band of Broca and of the substantia innominata in the rat: an anatomical study using the anterograde transport of a conjugate of wheat germ agglutinin and horseradish peroxidase

The projections of the nucleus of the diagonal band of Broca and of the substantia innominata to the cerebral cortex were studied in the rat, using the anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase. Following diagonal band injections, fibers were observed ascending in the septum and reaching the cingulate cortex. They had a rostrocaudal, horizontal direction, mostly in layer VI and could be followed over long distances on sagittal sections. The fibers gave off collaterals which were seen ascending in the cerebral cortex and reaching more superficial layers. Following substantia innominata injections, fibers were observed to take two routes: the first one identical to the one described above and a second through the caudate-putamen reaching the temporo-insular cortex. Terminal fields had a more diffuse distribution following substantia innominata than following diagonal band injections. No clear laminar pattern of termination was observed. However the density of terminals was higher in layers IV, V and VI than in layers I, II and III. Since the conjugate used is not taken up by fibers of passage, this pattern of connection is believed to reflect the organization of the projection of the nucleus of the diagonal band and of the substantia innominata to the cerebral cortex.     

A projection from acetylcholinesterase-containing neurones in the diagonal band to the occipital cortex of the rat

Injections of horseradish peroxidase made into occipital cortex of rat label, after axoplasmic transport, neurones in the nucleus of the diagonal band. Electron microscopy and acetylcholinesterase histochemistry reveal that the horseradish peroxidase-labelled cells belong to a neurone population with a distinct morphology and a high content of acetylcholinesterase. The possibility of these neurones providing the cortex with a cholinergic input was discussed.     

Functional and neurochemical cortical cholinergic impairment following neurotoxic lesions of the nucleus basalis magnocellularis in the rat

The effect of kainic and quinolinic acid on cortical cholinergic function was examined following injections of these agents into the nucleus basalis magnocellularis (nbm) or into the frontoparietal cortex. The release of cortical ³H-acetylcholine (³H-ACh), high affinity choline uptake (HACU) and acetylcholinesterase was measured 7 days following injections of saline (control), kainic acid (4.7 nmoles) and quinolinic acid (60, 150 and 300 nmoles) into the nbm. These cortical cholinergic parameters were also examined after injections of saline (control), kainic acid (9.4 nmoles) and quinolinic acid (300 nmoles) into the fronto-parietal cortex. The release of ³H-ACh, HACU and AChE was significantly reduced in animals injected with kainic or quinolinic acid into the nbm. Histological examination of stained sections showed a loss of cell bodies in the region of the nbm and the globus pallidus. The size of the lesion produced by quinolinic acid was proportional to the dose injected into the nbm. In animals injected with kainic acid or quinolinic acid into the cerebral cortex, the release of ³H-ACh, HACU and AChE was not significantly reduced when compared with control animals, although histological examination of stained cortical sections showed a marked loss of cortical neurons. Th results show that quinolinic acid, an endogenous neuroexcitant, produces a deficit of cholinergic function similar to that described in the cortical tissue of patients with senile dementia of Alzheimer's type. The toxic effects of quinolinic acid on cortical cholinergic function are due to its action on cholinergic cell bodies in the nbm. The cortical slice preparation from quinolinic acid-treated animals showing impairment of ³H-ACh release, may be useful in assessing the action of drugs designed to improve cholinergic function.     

The corticopontine projection: axotomy-induced loss of high affinity L-glutamate and D-aspartate uptake, but not of gamma-aminobutyrate uptake, glutamate decarboxylase or choline acetyltransferase, in the pontine nuclei

The corticopontine fibres were severed in the crus cerebri in rats and mice by a stereotaxically operated retractable wire-knife. The pontine nuclei were microscopically dissected from fresh slices of rats and synaptosome-containing homogenates were prepared. The high affinity uptake of radiolabelled L-glutamate (L-Glu) and D-aspartate (D-Asp) was heavily reduced five days after the lesions. The uptake was further reduced after bilateral (-75% for D-Asp and -65% for L-Glu) than after unilateral lesions (-55% for D-Asp and -45 to 50% for L-Glu on the lesioned side.) The molar ratio of the uptakes of D-Asp and L-Glu was consistently lower in pons after transection of the cortical afferents than normally (-28% after bilateral lesions). gamma-Aminobutyrate uptake and glutamic acid decarboxylase were not changed. Choline acetyltransferase was increased (+53%) after unilateral lesions, but not altered after bilateral lesions. Autoradiograms of slices from mice, incubated with tritium-labelled amino acids and fixed in glutaraldehyde, showed high affinity uptake sites for D-Asp to be enriched in the pontine nuclei, compared to neighbouring structures. After partial lesion of the crus cerebri the uptake was reduced in the area with degenerated corticopontine afferents. gamma-Aminobutyrate uptake sites were relatively less concentrated in the pontine nuclei than D-Asp uptake sites. The results indicate, along with the previous demonstration of Ca-dependent K-induced release of D-[3H]aspartate from the corticopontine terminals, that glutamate and/or aspartate may be transmitters in this pathway. The results also suggest that acidic amino acid uptake sites may differ in their relative transport rates for aspartate and glutamate.     

The septohippocampal projection in the rat: an electron microscopic horseradish peroxidase study

In order to identify the specific targets of the septohippocampal projection in the rat, horseradish peroxidase localization at the electron microscopic level was used. Following injections of free horseradish peroxidase into the medial septum, sections of the dorsal hippocampal formation were reacted with diaminobenzidine and processed for electron microscopy by routine methods. Sections were viewed unstained. Horseradish peroxidase labeling in the dentate gyrus was predominantly in the supra- and infragranular layers. All postsynaptic elements were neuronal. They included granule cell somata and somata and dendrites of hilar cells; these may include pyramidal basket cells. No synaptic contacts with vascular or glial elements were found. These results provide a basis for comparing the specific targets of the septohippocampal projection with those of the sympathohippocampal pathway, which innervates the dentate following lesions of the septohippocampal projection.     

Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase

The neurochemical identity of ascending putative cholinergic pathways from the rat basal forebrain was investigated employing a method for simultaneously visualizing choline acetyltransferase immunoreactivity and retrogradely transported horseradish peroxidase-conjugated wheatgerm agglutinin. This histochemical procedure revealed three distinct populations of neurons: (1) cells which stained only for choline acetyltransferase immunoreactivity; (2) cells which stained only for retrograde tracer and (3) cells which stained simultaneously for choline acetyltransferase immunoreactivity and retrograde tracer. The results demonstrated that this projection is topographically organized and consists of both cholinergic and noncholinergic components. The relative contribution of each component varied with the telencephalic target area as follows: the olfactory bulb receives a projection from cells of the horizontal limb nucleus, 10-20% of which are cholinergic (Ch3); the hippocampal formation receives afferents from cells of the medial septal and vertical limb nuclei, 35-45% of which are cholinergic (Ch1 and Ch2); and the cortical mantle receives afferents primarily from cells within the substantia innominata-nucleus basalis complex, 80-90% of which are cholinergic (Ch4). The topographical organization of Ch4 projections is not as completely differentiated as we have previously observed in the primate.     

Observations on the morphology and histochemistry of the rat neostriatum in tissue culture.

Cells from the neostriatum of newborn rats were cultured for 30 daysin vitro. The morphology of the cultures was studied using light and phase contrast microscopy and fluorescence microscopy. The studies were completed by demonstration of monoamine-oxidase, acetylcholinesterase and alkaline phosphatase enzyme activities. During the culture period cells possessing the characteristics of mature neurons were observed. Most neurons were small to medium-sized bipolar or tripolar cells but large nerve cells were few in number. Some neurons showed a distinct acetylcholinesterase activity in the cytoplasm. Monoamine-oxidase activity was observed in both neurons and non-neural cells. Alkaline phosphatase activity was present on the surface of some flat cells, although many similar cells were devoid of activity. No catecholamine fluorescence was seen in the cultured cells but neurons as well as glial cells and flat non-neural cells took upl-DOPA. Some cells also took up dopamine at low concentrations.Several different transmitter mechanisms are involved in the neuronal organization of the neostriatum and its related regions so that its morphology is difficult to define. However, the present work shows that tissue culture is a possible approach to the study of the instrinsic neuronal organization of the neostriatum.     

Cortical relay neurons and interneurons in the N. ventralis posterolateralis of cats: a horseradish peroxidase, electron-microscopic, Golgi and immunocytochemical study

After injections of horseradish peroxidase involving the whole primary (SI) and secondary somatosensory (SII) areas of adult cats, 16-21% out of 2220 counted neurons in the nucleus ventralis posterolateralis were unlabelled. The mean areas of perikarya of these neurons varied between 111.8 +/- 32.3 microns2 and 180.8 +/- 48.6 microns2. The size of perikarya of retrogradely-labelled neuron ranged from 256.9 +/- 100.4 microns2 to 409 +/- 163 microns2. Retrogradely-labelled and unlabelled neurons were examined under light- and high-voltage electron-microscopy. Besides 'large', mainly multipolar or oval fusiform perikarya, retrogradely-labelled neurons may display perikarya of 'small' size. Both types of neurons correlate well with Golgi-impregnated cells with a tufted dendritic pattern usually identified as thalamocortical neurons. On the other hand, the size and morphology of perikarya and initial dendrites of neurons unlabelled by retrograde transport of horseradish peroxidase correlate well with that of Golgi-impregnated neurons which are markedly different from the thalamocortical neurons, have very characteristic and profuse dendritic appendages and have been identified by previous investigators as Golgi Type II neurons. In order to probe further whether these may correspond to the GABAergic interneurons proposed by previous evidence, an immunocytochemical approach was also applied at the light- and electron-microscope level, using an antiserum prepared in sheep against rat brain glutamate decarboxylase. By this method it is shown that 19-21% of neurons in the nucleus ventralis posterolateralis of adult cats are glutamate decarboxylase-positive and that the perikaryal size of these labelled neurons ranges between 134.6 +/- 44.5 microns2 and 164.4 +/- 47.3 microns2. Histogram distribution of the number and areas of the counted immunoreactive neurons closely matches that of unlabelled neurons in experiments with retrograde transport of horseradish peroxidase. The results give support to previous evidence suggesting that part of population of neurons in the nucleus ventralis posterolateralis is represented by a distinct class of neurons which are apparently GABAergic.     

A second type of striatonigral neuron: a comparison between retrogradely labelled and Golgi-stained neurons at the light and electron microscopic levels

In a light and electron microscopic examination of the neostriata of rats that had received injections of horseradish peroxidase into the ipsilateral substantia nigra, two morphologically distinct types of horseradish peroxidase-labelled neurons were observed. In confirmation of previous findings, one type was of medium-size and was characterized by Golgi-staining and gold-toning as the densely spinous type. The second type of neuron was in contrast, larger, had an indented nucleus and numerous cytoplasmic organelles. The synaptic input to the perikarya of the latter neurons consisted of numerous boutons containing large round and oval vesicles. The boutons formed symmetrical synaptic contacts and were similar to those of the local axon collaterals of medium-size densely spiny striatonigral neurons.In an attempt to establish what type of Golgi-impregnated neuron the second type of horseradish peroxidase-labelled neuron was, seventeen Golgi-stained or gold-toned neurons were examined in the electron microscope. Three of them were very similar in their ultrastructural features and synaptic input to the horseradish peroxidase-labelled neurons. All three were of a similar morphological appearance in the light-microscope and characteristically had long (up to 700 μm), essentially smooth dendrites. Both the large horseradish peroxidase-labelled neurons and the Golgi-impregnated neurons with long dendrites have so far only been found in the most ventral regions of the neostriatum.It is concluded that there are at least two morphologically distinct types of striatonigral neurons.