Monkey Neostriatum Research Articles

Coding of efferent signals in monkey neostriatum.

Coding of efferent signals in monkey neostriatum.

Technique for Bilateral Intracranial Implantation of Cells in Monkeys Using an Automated Delivery System

Intracerebral grafting combined with gene transfer may provide a powerful technique for local delivery of therapeutic agents into the CNS. The present study was undertaken to: (i) develop a reliable and reproducible automated cell implantation system, (ii) determine optimal implantation parameters of cells into the striatum, (iii) determine upper safe limits of cellular implantation into the neostriatum of monkeys. Autologous fibroblasts were infused into six sites of the striatum in nonhuman primates (Macaca mulatta, n = 11). Twenty-six-gauge cannulae were inserted vertically through cortical entry sites into the striatum (two sites in the caudate nucleus and four sites in the putamen) at predefined coordinates based on magnetic resonance imaging (MRI). The cannulae were guided by an electronically operated, hydraulic micropositioner and withdrawn at controlled rates, while cells (5, 10, 20, 40, or 80 microl/site) were infused simultaneously. Varying infusion rates and cell concentrations were also evaluated. Visualization and evaluation of graft placement were performed using contrast MRI at 3-5 days postsurgery. Animals were monitored for signs of clinical complications and sacrificed 2 weeks following surgery. Postimplantation MRI revealed a tissue mass effect of the implant with shifting of midline, edema, and infiltration of the white tracts at 40 and 80 microl/site. In addition, these animals developed transient hemiparesis contralateral to the implant site. MRI of animals grafted with 20 microl/site exhibited columnar-shaped implants and evidence of infiltration into white matter tracts possibly due to a volume effect. No clinical side effects were seen in this group. At 14 days postsurgery, MRI scans showed consistent columnar grafts (measuring approximately 5 mm in height) throughout the striatum in animals implanted with 5 or 10 microl/site. No signs of clinical side effects were associated with these volumes and postmortem histological examination confirmed MRI observations. Optimal surgical parameters for delivery of cells into the striatum consist of a graft volume of 10 microl/site, an infusion rate of 1.6 microl/min, a cell concentration of 2.0 x 10(5) cells/microl, and a cannula withdrawal rate of 0.75 mm/min. These results show that infusion of cells into the striatum can be done in a safe and routine manner.

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.

Rhythmically firing neostriatal neurons in monkey: activity patterns during reaction-time hand movements.

While previous studies have identified rhythmically firing neurons (RFNs) in monkey neostriatum and these rhythmic firing patterns have been shown to evolve in neostriatal tonically active neurons (TANs) after dopamine input depletion, the activity patterns of RFNs during motor behavior are still far from completely understood. We examined the single-unit activity patterns of neostriatal neurons, recorded in awake behaving monkeys during a wrist movement task, for evidence of rhythmic activity. Monkeys made ballistic wrist flexion and extension movements in response to vibrotactile cues. Animals held a steady wrist position for 0.5 to 2.0 s while awaiting the onset of the go-cues (hold period). Although the majority of neostriatal neurons (274/306) did not fire rhythmically, approximately 10% of the neurons (32/306) fired rhythmically at 10-50 Hz during the hold period. Most RFNs (28/32) showed significant activity changes during the time between go-cue presentation and movement onset (premovement activity). One-half of RFNs exhibited premovement activity that differed as a function of movement direction. Only one RFN may have responded to the delivery of a fruit juice reward. Neuronal firing was analyzed using interspike interval distributions, autocorrelations, and serial correlation techniques. These analyses showed that the activity patterns of most RFNs were consistent with an integrate-and-fire model of neuronal rhythm generation. Changes in RFN activity patterns during the premovement interval and intertrial variations in firing frequency could be explained by changes in the general level of excitatory input. These observations are consistent with the firing properties reported for neostriatal cholinergic interneurons. It has been suggested that tonically active neurons may be cholinergic interneurons and that these neurons show changes in activity related to specific aspects of behavioral paradigms, such as rewards. RFNs may constitute a special class of TANs. The results presented here suggest that RFNs may have a role in movement initiation. We speculate that RFNs may modulate the propagation of cortical oscillations via basal ganglia-thalamic-cortical loops.

Correlates of sequential elements of bimanual behavior in the neuronal activity of the neostriatum in monkeys.

Neuron spike activity was recorded in the putamen of monkeys trained to perform bimanual operant behavior consisting of nine separate steps. Neuronal reactions were present at all steps: in 52-62% of cases during movement, and in 27-36% of cases during responses to the trigger and conditioned signals and as the monkeys decided which was the working hand. The proportion of inhibitory responses to the trigger stimulus was 9%, while inhibitory reactions accounted for 68% of reactions during hand movement in response to the conditioned signal, 33% of reactions when this same hand was used to collect food reinforcement, and 33% of reactions during simultaneous movement of both hands. Reactions significantly differentiating between right- and left-sided tasks were seen at all stages of working-hand decision-taking and in reactions to the signal indicating the correctness of the selection, but were not seen for reactions to the conditioned signal or for activity accompanying movements of one of the animal's hands. These data provide evidence indicating that each step of the complex operant behavior, individual systems of putamen neuronal reactions were created with qualitatively different integral sensitivity to instantaneous behavior.

Projections from the visual areas to the neostriatum in rats. A re-examination.

Neostriatal afferents from the primary visual cortex in rats were studied using dextran-biotin, biocytin, and Fluoro-Gold. The area V1 was found to project only to a dorsomedial, longitudinal region of neostriatum (NS), bordering on the lateral ventricle and subcortical white matter. The preterminal fibres in the NS form fluffs which increase in number and density in the cases with larger injections. This target region is poorly stained for calbindin and yet belongs to the matrix compartment. The secondary visual areas also project to the dorsomedial NS region but they also innervate the deeper tissue in the same general region. Iontophoresis of Fluoro-Gold into the dorsomedial NS labelled some pyramidal neurones in the fifth layer of the primary visual cortex. The cortical areas that surround the visual cortical complex project to other regions of the NS: the somatosensory cortex to a dorsolateral longitudinal region and the auditory area to the medial half of the caudalmost portion of NS. Thus, major sensory cortical divisions project to non-overlapping NS regions. Since NS in monkeys and cats does not receive afferents from the primary visual cortex and in a number of other species does, we conclude that visual systems in different mammals differ with respect to their projections to NS.

Reflection of internal and external determinants of behavior in the neuronal activity of the neostriatum of monkeys.

It has been demonstrated that some neurons of the neostriatum of monkeys (Macaca nemestrina) participate in supporting the reaction of the animal to the appearance of standard situations in which a decision is made on the basis of already existing skills. Other neurons (primarily non-baseline active), by contrast, are activated in nonstandard situations, when the use of existing skills is ineffective. It is hypothesized that their activity is associated with the shift of the animal to a different activity which consists in the rejection of the use of existing skills for the formation of new skills.

Spiny and aspiny types of neuropeptide Y immunoreactive neurons in the monkey neostriatum

The present study demonstrates the existence of two types of neurons with neuropeptide Y (NPY) immunoreactivity in the neostriatum of the monkey ( Macacus fuscatus) by using the avidin-biotin-immunoperoxidase method. One type, accounted for about 80% of striatal NPY cells, corresponded to the medium-sized aspiny type neurons. The other type resembled the medium-sized, spiny type II neurons. These findings suggest that there are at least two functional subpopulations of NPY neurons in the monkey neostriatum.

Characteristic features of NPY immunoreactive neurons in the monkey neostriatum : Hiroshi Takagi, Yoshiyuki Kubota, and Shinobu Inagaki, First Department of Anatomy, Osaka City University Medical School, 1-4-54 Asahi-machi, Abeno-ku, Osaka 545 and Second Department of Anatomy, Osaka University Medical School, 4-3-57 Nakanoshima, Kita-ku, Osaka 530, Japan

Characteristic features of NPY immunoreactive neurons in the monkey neostriatum : Hiroshi Takagi, Yoshiyuki Kubota, and Shinobu Inagaki, First Department of Anatomy, Osaka City University Medical School, 1-4-54 Asahi-machi, Abeno-ku, Osaka 545 and Second Department of Anatomy, Osaka University Medical School, 4-3-57 Nakanoshima, Kita-ku, Osaka 530, Japan

Characteristic features of NPY immunoreactive neurons in the monkey neostriatum

Characteristic features of NPY immunoreactive neurons in the monkey neostriatum

GABAergic elements in the neuronal circuits of the monkey neostriatum: a light and electron microscopic immunocytochemical study.

An antibody raised in rabbits against a GABA-BSA conjugate was used together with the PAP technique to label elements in the neostriatum of three Old World monkeys. Light microscopy revealed numerous immunoreactive medium-size neurons of various staining intensities, some of which had indented nuclei, as well as an occasional large cell. The neuropil showed a plexus of fine processes with frequent puncta. Ultrastructurally, the medium-size GABA-positive neurons were of two types: one with smooth nuclei and scanty cytoplasm, similar to spiny I cells, the other with invaginated nuclear envelopes and more abundant perikaryon, resembling the aspiny type. Correspondingly, labeled dendrites were either spiny or varicose. Some stained axons were myelinated, and the boutons had either large and ovoid, or small and pleomorphic vesicles. All of these boutons formed symmetric synapses, the former type with GABA-positive dendritic shafts but also with unlabeled dendrites; the latter type usually with GABA-negative elements, either dendrites, dendritic spines, or somata. Synapses were also observed between unreactive boutons and immunostained dendrites. Terminals with densely packed, small round vesicles that established asymmetric synapses with spines were always GABA-negative. Glial elements were consistently unlabeled, save for some astroglial endfeet. These findings provide positive evidence for the existence of two classes of GABAergic striatal neurons corresponding to a long-axoned spiny I type and an aspiny interneuron. Furthermore, the simultaneous labeling of GABA-immunoreactive presynaptic and postsynaptic profiles offers possible morphologic bases for the various kinds of intrastriatal inhibitory processes, including the feedforward, feedback, and "autaptic" types.

Synaptic organization of cholinergic neurons in the monkey neostriatum.

Cholinergic neurons in the monkey neostriatum were examined at the light and electron microscopic level by immunohistochemical methods in order to localize choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. At the light microscopic level a sparse distribution of cholinergic neurons was identified throughout the caudate nucleus. Neurons had large (25-30 microns) somata, eccentric invaginated nuclei, primary dendrites of unequal diameters, and varicosities on distal dendritic branches. Ultrastructural study showed that the cholinergic cells had a cytoplasm abundant in organelles. Within dendritic branches, mitochondria and cisternae were localized primarily to varicosities. Synaptic inputs were distributed mostly to the dendrites and at least four types that formed symmetric or asymmetric synapses were observed. Immunoreactive fibers were relatively numerous within the neuropil and exhibited small diameters (0.1-0.15) micron) and swellings at frequent intervals. Cholinergic boutons that formed synapses were compared to unlabeled terminals making asymmetric synapses with dendritic spines. Results showed that ChAT-positive axons had significantly smaller cross-sectional areas, shorter synaptic junctions, and a higher density and surface area of mitochondria than the unlabeled boutons. Cholinergic axons formed symmetric synapses mostly with dendritic spines (53%) and the shafts of unlabeled primary and distal dendrites (37%). A relatively small proportion of the boutons contacted axon initial segments (1%) and cell bodies (9%) that included medium-sized neurons with unindented (spiny) and indented (aspiny) nuclei. The majority of dendritic spines contacted by cholinergic axons were also postsynaptic to unlabeled boutons forming asymmetric synapses. The results suggest that cholinergic neurons in the primary neostriatum belong to a single morphological class corresponding to the large aspiny (type II) interneuron identified in previous Golgi studies. Present results along with earlier Golgi-electron microscopic observations from this laboratory suggest that neostriatal cholinergic cells integrate many sources of intrinsic and extrinsic inputs. The observed convergence of ChAT-immunoreactive boutons and unlabeled axons onto the same dendritic spines suggests that intrinsic cholinergic axons modulate extrinsic inputs onto neostriatal spiny neurons at postsynaptic sites close to the site of afferent input.

Ultrastructure of Golgi-impregnated and gold-toned spiny and aspiny neurons in the monkey neostriatum.

Golgi-impregnated, gold-toned spiny and aspiny neurons in the monkey neostriatum were deimpregnated and examined at the electron microscope level. Spiny type I neurons have relatively large nuclei with few indentations and aggregates of chromatin under the nuclear membrane which in some regions give the appearance of a dark rim. The small quantity of surrounding cytoplasm is poor in organelles. Aspiny type I neurons have eccentric, highly indented nuclei. The relatively large proportion of cytoplasm is rich in organelles especially Golgi apparatus and rough endoplasmic reticulum which often appears in stacks. Synapses with symmetric membrane densities are common on the somata of spiny type I neurons. Those on the proximal and distal dendritic shafts are few in number and asymmetric, and those on spines more frequent and primarily asymmetric. Aspiny type I neurons have few synapses on their cell bodies. Proximal and distal dendrites, however, are contacted by numerous profiles which contain small round vesicles and make both symmetric and asymmetric synapses. The same axon terminals also synapse with dendritic spines of spiny neurons, indicating that an input, most likely of afferent origin, is shared by both cell types. Other less frequently occurring profiles forming symmetric membrane densities also contact the dendrites of aspiny and spiny neurons. The axon hillocks and initial segments of both neuronal types receive a synaptic input, which is more common on spiny cells. Results offer unequivocal evidence for the differences in the ultrastructure of these two most common categories of medium-size neostriatal neurons, which may help in their proper identification in standard material, as well as information on the types and distributions of synaptic inputs onto these neurons. Moreover, the findings clarify some controversies in the literature probably originating from observations on a mixed population of cells of medium size.

A golgi study of afferent fibers in the neostriatum of monkeys

A golgi study of afferent fibers in the neostriatum of monkeys

A Golgi study of neuronal types in the neostriatum of monkeys

Examination of the neostriatum of monkeys prepared by the Golgi-Kopsch perfusion method revealed the presence of at least 6 neuronal types. The spiny type I is medium size with a high density of dendritic spines. The axon extends well beyond the dendritic field and gives off many collaterals. The spiny type II is either medium or large size, has long thick dendrites with a relatively low density of spines, and an axon similar to that of the previous type but with fewer collaterals. The aspiny type I is medium size with varicose dendrites and a thin axon arborizing in the immediate vicinity of the soma. The aspiny type II is large, with many thick and thin varicose dendrites. The aspiny type III is medium size with smooth dendrites and an axon ramifying profusely within the dendritic field. The neurogliform cell is small with many branching processes. Findings indicate that the neostriatum has 2 distinct types of spiny neurons with long axons (spiny I and II), some of which may contribute to the efferent systems. There are also 2 (aspiny I and III) or perhaps as many as 4 categories (aspiny I, II, III and neurogliform) of typical Golgi type II cells. Large neurons belong to 2 separate populations, one with dendritic spines and a long axon (large version of spiny II), and one with varicosities and presumably a short axon (aspiny II). A realistic interpretation of neurophysiologic data on the neostriatum must take into account all cell types instead of the current view of considering it as a pool of interneurons with few output cells.