Involvement of human basal ganglia in offline feedback control of voluntary movement

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.     

Cholinergic modulation of skill learning and plasticity

The basal forebrain cholinergic system strongly influences both cortical plasticity and learning. Directly relating these two roles has proven difficult. New results indicate that nucleus basalis lesions prevent motor cortex map plasticity and impair skill learning. These results strengthen the hypothesis that nucleus basalis gates neural plasticity necessary for instrumental learning.     

Auditory-vocal cholinergic pathway in the songbird brain

Male zebra finches learn to imitate a tutor's song through auditory and motor learning. The two main song control nuclei in the zebra finch forebrain, the higher vocal center (HVC) and the robust nucleus of the archistriatum (RA), receive cholinergic innervation from the ventral paleostriatum (VP) of the basal forebrain which may play a key role in song learning. By injecting neuroanatomical tracers, we found a topographically segregated pathway from nucleus ovoidalis (Ov) to VP that in turn projects in a topographic fashion to HVC and RA. Ov is a major relay in the main ascending auditory pathway. The results suggest that the cholinergic neurons in the VP responsible for song learning are regulated by auditory information from the Ov.     

大鼠纹状体边缘区与Meynert氏基底核的突触联系及其与学习记忆功能的关系——WGA-HRP束路追踪法、电镜法和行为实验法研究

纹状体边缘区（ＭｒＤ）是我们先后在大鼠、猫和猴脑内新发现的一个区域。它是位于纹状体尾内侧、环绕着苍白球头外侧的一层梭形细胞。ＭｒＤ的细胞构筑、免疫组化特性和纤维联系形式不同于纹状体其它区。ＭｒＤ的离心投射终止在苍白球尾侧,接近Ｍｅｙｎｅｒｔ基底核（ＮＢＭ）附近。损毁双侧ＭｒＤ后,动物的学习记忆功能减弱。ＮＢＭ已知与动物智能有关。本研究用纤维溃变和束路追踪电镜法结合行为实验方法,旨在了解ＭｒＤ与ＮＢＭ之间有无突触联系,以及此种联系与动物学习记忆的关系。用纤维溃变和束路追踪电镜法研究表明,由ＭｒＤ发出的纤维终末与ＮＢＭ的胆碱能神经元胞体间存在着突触联系。损伤ＭｒＤ造成ＭｒＤ和ＮＢＭ形成突触联系的终末溃变后,动物的学习记忆能力降低。研究结果表明边缘区与Ｍｅｙｎｅｒｔ基底核间存在着突触联系,而这种联系很可能是ＭｒＤ的学习记忆功能的结构基础之一。     

Surprised at all the entropy: hippocampal, caudate and midbrain contributions to learning from prediction errors

Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts.     

Development of the accessory glands in the genital tract of female Teleogryllus commodus WALKER (Insecta, Orthoptera)

The development of the female accessory glands in Teleogryllus commodus was studied by detailed morphometric and stereological analyses. In addition, a microsurgical method was developed to quantify the gland secretion. The morphometric results yield evidence that the glands are subject to a significant growth during peak differentiation, starting immediately after the adult moult. The gland growth is exclusively caused by a hypertrophy of single gland cells with respective volume gains between 400 and 700%. According to the stereological results, the volume of mitochondria per cell is marked by an up to fourfold increase during peak differentiation. Other cell structures (rER, sER) are characterized by a similar propagation behavior. The nucleus and nucleolus grow simultaneously with the cell, indicating high production of site-specific macromolecules. Infolds of the basal cell membrane cause a progressive enlargement of the basal cell surface ensuring an increased uptake of secretory precursors from the hemolymph. Quantitative studies show that the total production of secretion increases with proceeding age and can be correlated with a rising egg-laying activity, starting on the eighth day of adult's life. This underlines the main function of the secretion as a lubricant for a facilitated transport of the eggs through the ovipositor.     

Complementary 'bottom-up' and 'top-down' approaches to basal ganglia function

Recently, two quite different approaches exemplifying 'bottom-up' and 'top-down' philosophies have shed new light on basal ganglia function. In vitro work using organotypic co-cultures has implicated the subthalamic nucleus (STN) and the external segment of the globus pallidus (GP(e)) as pacemakers for low-frequency bursting that is reminiscent of the activity produced in Parkinsonian tremor. A circuit essential for avian song learning has been identified as part of the basal ganglia with surprisingly well conserved cellular details; investigation of this system may help to address general issues of basal ganglia function.     

Common features of neural activity during singing and sleep periods in a basal ganglia nucleus critical for vocal learning in a juvenile songbird

Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase.     

Effect of psychotropic drugs on 3,4-dihydroxyphenylacetic acid (DOPAC) content in the medial basal hypothalamus

The effect of different psychotropic drugs on 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the medial basal hypothalamus has been studied by the use of a very sensitive radioenzymatic method. Apomorphine and haloperidol, which are known to respectively decrease and increase DOPAC levels in the caudate nucleus, fail to influence DOPAC level in the medial basal hypothalamus. Reserpine, which increases DOPAC level in the caudate nucleus, decreases it in the medial basal hypothalamus. Amphetamine decreases DOPAC level in the medial basal hypothalamus as it does in the caudate nucleus. These results suggest that DA metabolism in the medial basal hypothalamus is controlled by mechanisms different from those operating in other brain areas.     

Configuration of the magnocellular nuclei in the basal forebrain of the human adult

With the use of gapless series of thick sections (800 microns) stained for lipofuscin pigment as a stable intraneuronal characteristic, it was found in the human brain that the three magnocellular nuclei in the basal forebrain-the medial septal nucleus, the nucleus of the diagonal band (vertical and horizontal limb) and the basal nucleus of Meynert located within the substantia innominata-were tightly connected with each other. A band-like anteromedial subnucleus and a semilunar posterolateral subnucleus could be delineated in the basal nucleus and were found to be embedded in a zone of low cell density, the substantia innominata, which medially blends into the horizontal limb of the diagonal band nucleus. A three-dimensional reconstruction was made to demonstrate the complex shape of the magnocellular basal forebrain nuclei.     

The ultrastructure of the Sertoli cell of the vervet monkey, Chlorocebus aethiops

The ultrastructure of the Sertoli cell of the vervet monkey was studied using both scanning and transmission electron microscopic techniques. SEM micrographs revealed perforated sleeve-like processes which encased mature elongated spermatids which are ready for spermiation. TEM micrographs showed a large Sertoli cell nucleus characterized by many lobes (4–5) and consisting of a homogenous nucleoplasm and a distinctive nucleolus. The nucleus occupies a significant portion of the basal region of the cell. The distribution of chromatin clearly shows high activity of these cells. Lipid droplets and free ribosomes are also found scattered throughout the cytoplasm. Well-developed Golgi apparatus is found in the basal region of the cell. There is phagocytic activity in the Sertoli cells as revealed by the presence of numerous phagosomes. Numerous mitochondria with well-developed tubular cristae are found on the basal side of the nucleus, whereas few mitochondria are located on the apical side of the nucleus. Distinct desmosomes are located between cells. A well-developed smooth endoplasmic reticulum and granular endoplasmic reticulum are frequently found in the cytoplasm of the Sertoli cells. The results of this investigation showed that Sertoli cells of the vervet monkey are almost similar to those of humans and show many similarities with other mammalian species.     

Marginal division of the neostriatum: A subcortical memory center

The marginal division (MrD) is a pan-shaped subdivision in the caudal margin of the neostriatum newly discovered in the brains of the rat, cat, monkey and humans. A variety of intensely expressed neuropeptides and monoamines and their receptors were identified in the fibers, terminals and neuronal somata in the MrD with immunohistochemical and patch clamp methods. The MrD was shown to be involved in learning and memory by double-blind studies of Y-maze learning and long-term potentiation in rats. c-Fos expression and tract-tracing techniques with immunoelectronmicroscopy indicated that the MrD is a new component of the limbic system and is a key linking area between the limbic system and the basal nucleus of Meynert. Functional magnetic resonance image (fMRI) studies illustrated that the MrD and the prefrontal cortex are involved in digital working memory in the human brain. A cerebral hemorrhage case report confirmed the findings with fMRI. In conclusion, based on the position of the MrD, its advanced development in higher mammalian brains, abundant blood supply and diverse connections with other memory-related structures, MrD is likely to be an important subcortical center of learning and memory.     

Behaviors of nucleus, basal bodies and microtubules during eupyrene and apyrene spermiogenesis in the silkworm, Bombyx mori (Lepidoptera)

Observations with immunostaining for tubulin and electron microscopy revealed that silkworm eupyrene spermiogenesis was characterized by an attachment of the basal body to the nucleus except in the period of movement for unidirectional arrangement. In young eupyrene sperm, a microtubule basket caught the nucleus, which thereafter was transformed elliptically. Microtubules were also observed along the elongated acrosome and mitochondrial derivatives. During apyrene spermiogenesis, however, the basal body was not attached to the nucleus and approached the head cyst cell after the completion of unidirectional arrangement, leaving the round nucleus in the middle of the cell. The presence or absence of the phenomenon in which the basal body attaches to the nucleus seems to be essential in the course of diverse spermatogenesis of the silkworm.     

Basal ganglia influences on the cerebellum of the cat

The changes in firing rate of intracerebellar nuclear neurons following electrical stimulation of the contralateral basal ganglia were investigated in adult cats, in which antidromic activation of cortico-pontine and/or cortico-olivar fibers arising in the area 6 had been excluded by chronic ablation of the motor cortex. Activation of putamen and caudate nucleus induced discharge changes in a low percentage (below 12.5%) of both medial and lateral cerebellar nuclei neurons, while stimulation of globus pallidus and especially of entopeduncular nucleus modified the spontaneous discharge of a greater percent of cells (up to 29%), mainly in the most lateral cerebellar portions. The basal ganglia-induced effects were abolished upon section of the brachium pontis but not of the restiform body. Latency values of the responses, which were predominantly excitatory in nature, suggest the involvement of structures interposed between basal ganglia and precerebellar systems. We postulated that impulses issued by the basal ganglia could reach the cerebellum through a pathway that involves the pedunculopontine nucleus and the nucleus reticularis tegmenti pontis.     

Complementary ‘bottom-up’ and ‘top-down’ approaches to basal ganglia function

Recently, two quite different approaches exemplifying ‘bottom-up’ and ‘top-down’ philosophies have shed new light on basal ganglia function. In vitro work using organotypic co-cultures has implicated the subthalamic nucleus (STN) and the external segment of the globus pallidus (GP_e) as pacemakers for low-frequency bursting that is reminiscent of the activity produced in Parkinsonian tremor. A circuit essential for avian song learning has been identified as part of the basal ganglia with surprisingly well conserved cellular details; investigation of this system may help to address general issues of basal ganglia function.     

The action of sodium glutamate and acetylcholine on neurons of the basal amygdaloid nucleus after degeneration of hypothalamo-amygdaloid pathways

The chemoreactive properties of neurons of the rabbit basal amygdaloid nucleus were investigated at various times after unilateral division of all the direct hypothalamo-amygdaloid pathways (stria terminalis, ventroamygdalofugal pathway) and the anterior commissure. After immobilization with diplacin, the activity of the absolute majority of neurons of the partially deafferented basal nucleus (by contrast with responses of neurons of the intact amygdala) were inhibited by acetylcholine. Sodium glutamate caused facilitation of activity during electrophoresis, followed by inhibition. The results are compared with those obtained on neurons of long-isolated cortical slabs.     

Chromatin Arrangement and Axis Formation in the Spermiogenesis of a Pulmonate Snail

Nuclear change in relation to axis formation and condensation during spermiogenesis was investigated in the snail, Physa acuta. In the early spermatid, characteristic thick layers (termed apical and basal plates) are formed on two sides of a nuclear envelope. Soon after the formation of these plates, a developing acrosome and a flagellum attach externally to the center of the apical and basal plates, respectively. However, most (presumably all) of the chromatin filaments become attached all over the inner surface of the apical and basal plates. This means that the plates themselves are actually the specialized forms of the nuclear envelope to which chromatin filaments become connected; by means of these plates, the chromatin filaments become arranged in parallel to the antero-posterior axis as the nucleus elongates. This suggests that the formation of these two thick layers on opposing surfaces of the nucleus primarily determines the antero-posterior axis of the spermatid and the direction of the arrangement of chromatin.
The flattening of the nucleus prior to elongation is caused mainly by the enlargement of the basal plate. Subsequent nuclear shaping and condensation are discussed in relation to the change in the surface structures of the nucleus and the organization of the microtubules.     

Distribution of acetylcholinesterase and monoamine oxidase in the amygdala of the guinea pig

Summary A study of the amygdala of the guinea pig was carried out on material stained by the Nissl, acetylcholinesterase (AChE) and monoamine oxidase (MAO) methods. The material stained for Nissl substance was used primarily as a reference in determining the distribution of the two enzymes. Regional differences in cell size and/or distribution were noted within the lateral, basal, medial and cortical nuclei. In the AChE preparations, it was observed that the large-celled part of the basal nucleus stained very intensely, the small-celled part of the basal nucleus and ventromedial part of the lateral nucleus more moderately, and the dorsolateral part of the lateral nucleus and cortical nucleus lightly. The central and medial nuclei showed almost no reaction. With the MAO method, the greatest staining reaction was seen in the medial nucleus, the medial part of the cortical nucleus, the anterior amygdaloid area and the ventromedial wedge of the putamen adjacent to the central nucleus. In addition, fibres of the stria terminalis stained very darkly.These findings are discussed in relation to the observations of previous authors employing the same methods.Supported in part by the Canadian Medical Research Council Grant No. M.T. 870 and U.S. Public Health Service Grant No. NS-07998. This aid is gratefully acknowledged. We are indebted to Dr. Gorm Danscher for additional material and to Mr. A. Meier, Mrs. L. Munkøe, Mrs. K. Sørensen, Miss M. Sørensen, Miss D. Valgaard, and Miss B. Ørum for skillful assistance.     

Distribution of gastrin-releasing peptide immunoreactivity in the brain of the collared dove (Streptopelia decaocto)

The distribution of immunoreactivity after applying an antibody against gastrin-releasing peptide (GRP) was studied in the brain of the collared dove (Streptopelia decaocto). In the forebrain GRP-immunoreactive (GRP-ir) cells were found in the hyperstriatum accessorium, medial and lateral parts of the neostriatum, corticoidea dorsolateralis and temporoparieto-occipitalis areas, hippocampus, pre- and parahippocampal areas and prepiriform cortex. In the brainstem, GRP-ir cells were restricted mainly to the substantia nigra and ventral tegmental nucleus. Areas with densely packed GRP-ir clusters of varicosities were the medial intermediate hyperstriatum ventrale and lateral septal nucleus; dense GRP-ir neuropil was found in the parolfactory lobe, and in the dorsal half of the intermediate and caudal archistriatum. The ventral lamina medullaris contained many GRP-ir fibers. Forebrain areas devoid of immunoreactivity were the basal nucleus, ectostriatum, rostral archistriatum, most of the paleostriatum augmentatum and the lateral bed nucleus of the stria terminalis. Moderate densities of GRP-ir elements were found in the other telencephalic areas and further in, among others, the preoptic and hypothalamic region, ventral area of Tsai, cerulean nuclei, parabrachial complex, dorsal glossopharyngeal and vagus motor nuclei and medial nuclei of the solitary complex. The observations are compared with data from the literature and the implications for the definition of specific centers within the avian brain are discussed, with emphasis on systems with a role in visceral and motivational functions and in learning.     

The relationship between the proteolytic activity in the basal nuclei and locomotion in the open-field test under the conditions of an altered photoperiod

The effect of an altered photoperiod on the proteolytic activity in the basal nuclei, including the caudate nucleus, globus pallidus, nucleus accumbens, and amygdala complex, and rat behavior in the openfield test was studied. The altered photoperiod modulated the functional state of the basal nuclei, which was reflected in the locomotor activity of the animals.