Motor skill learning depends on protein synthesis in the dorsal striatum after training

Functional imaging studies in humans and electrophysiological data in animals suggest that corticostriatal circuits undergo plastic modifications during motor skill learning. In motor cortex and hippocampus circuit plasticity can be prevented by protein synthesis inhibition (PSI) which can interfere with certain forms learning. Here, the hypothesis was tested that inducing PSI in the dorsal striatum by bilateral intrastriatal injection of anisomycin (ANI) in rats interferes with learning a precision forelimb reaching task. Injecting ANI shortly after training on days 1 and 2 during 4 days of daily practice (n = 14) led to a significant impairment of motor skill learning as compared with vehicle-injected controls (n = 15, P = 0.033). ANI did not affect the animals’ motivation as measured by intertrial latencies. Also, ANI did not affect reaching performance once learning was completed and performance reached a plateau. These findings demonstrate that PSI in the dorsal striatum after training impairs the acquisition of a novel motor skill. The results support the notion that plasticity in basal ganglia circuits, mediated by protein synthesis, contributes to motor skill learning.     

Functions of dopamine in the dorsal and ventral striatum

Manipulations of dopamine levels in the dorsal and ventral striatum are shown to affect the activation of behaviour in distinct, yet parallel ways, which depend upon the nature of the neocortical and limbic input to these structures. Whereas dopamine in the dorsal striatum contributes to the sensorimotor co-ordination of consummatory behaviour and the development of a ‘response set’ in motor preparatory processes for skilled responses, dopamine in the ventral striatum influences the impact of reward-related stimuli on appetitive aspects of behaviour. The circumstances under which the striatal dopamine projections are normally active to effect these functions are defined by studies which attempt to correlate firing in single units or neurochemical indices of dopamine activity with environmental conditions, internal states and behaviour.     

Responses to reward in monkey dorsal and ventral striatum

Summary The sources of input and the behavioral effects of lesions and drug administration suggest that the striatum participates in motivational processes. We investigated the activity of single striatal neurons of monkeys in response to reward delivered for performing in a go-nogo task. A drop of liquid was given each time the animal correctly executed or withheld an arm movement in reaction to a visual stimulus. Of 1593 neurons, 115 showed increased activity in response to delivery of liquid reward in both go and nogo trials. Responding neurons were predominantly located in dorsal and ventromedial parts of anterior putamen, in dorsal and ventral caudate, and in nucleus accumbens. They were twice as frequent in ventral as compared to dorsal striatal areas. Responses occurred at a median latency of 337 ms and lasted for 525 ms, with insignificant differences between dorsal and ventral striatum. Reward responses differed from activity recorded in the face area of posterior putamen which varied synchronously with individual mouth movements. Responses were directly related to delivery of primary liquid reward and not to auditory stimuli associated with it. Most of them also occurred when reward was delivered outside of the task. These results demonstrate that neurons of dorsal and particularly ventral striatum are involved in processing information concerning the attribution of primary reward.     

A role for dorsal and ventral hippocampus in response learning

The hippocampus and the striatum have been traditionally considered as part of different and independent memory systems despite growing evidence supporting that both brain regions may even compete for behavioral control in particular learning tasks. In this regard, it has been reported that the hippocampus could be necessary for the use of idiothetic cues in several types of spatial learning tasks. Accordingly, the ventral striatum receives strong anatomical projections from the hippocampus, suggesting a participation of both regions in goal-directed behavior. Our work examined the role of the dorsal and ventral hippocampus on a response learning task. Cytochrome c oxidase (C.O.) quantitative histochemistry was used as an index of brain oxidative metabolism. In addition, determination of C.O. subunit I levels in the hippocampus by western blot analysis was performed to assess the contribution of this subunit to overall C.O. activity. Increased brain oxidative metabolism was found in most of the studied hippocampal subregions when experimental group was compared with a swim control group. However, no differences were found in the amount of C.O. subunit I expressed in the hippocampus by western blot analysis. Our results support that both the dorsal and ventral hippocampus are associated with the use of response strategies during response learning.     

Blockade of NMDA receptors 2A subunit in the dorsal striatum impairs the learning of a complex motor skill

Accumulating evidence proposes that the striatum, known to control voluntary movement, may also play a role in learning and memory. Striatum learning is thought to require long-lasting reorganization of striatal circuits and changes in the strength of synaptic connections during the memorization of a complex motor task. Whether the ionotropic glutamate receptor N-methyl-D-aspartate (NMDAR) contributes to the molecular mechanisms of these memory processes is still unclear. The aim of the present study was to investigate the role of striatal NMDAR and its subunit composition during the learning of the accelerating rotarod task in mice. To this end, we injected directly into the dorsal striatum of mice, via chronically implanted cannula, the NMDAR channel blocker MK-801 as well as the NR2A and NR2B subunit-selective antagonists NVP-AAM077 and Ro 25-6981, respectively, before rotarod training. There was no effect in the motor performances of mice treated with 1.0 μg/side of MK-801, 0.1 μg/side of NVP-AAM077, or 5 and 10 μg/side of Ro 25-6981. In contrast, injections of 2.5 and 5 μg/side of MK-801 or 0.5 and 1 μg/side of NVP-AAM077 impaired motor learning at Day 3 and 8. Interestingly, treatments with MK-801 and NVP-AAM077 did not alter the general motor capacities of mice as revealed by the stepping, wire suspension, and pole tests. Our study demonstrates that the NMDAR of the dorsal striatum contributes to motor learning, especially during the slow acquisition phase, and that NR2A subunits play a critical role in this process.     

The striatal mosaic in primates: patterns of neuropeptide immunoreactivity differentiate the ventral striatum from the dorsal striatum.

Patterns of immunoreactivity for calcium-binding protein, tyrosine hydroxylase and four neuropeptides in the ventral striatum (nucleus accumbens, olfactory tubercle and ventromedial parts of the caudate nucleus and putamen) were compared to patterns of these markers in the dorsal striatum (the majority of the neostriatum) in rhesus monkey. The striatal mosaic was delineated by calcium-binding protein and tyrosine hydroxylase immunoreactivities. Both markers were found preferentially in the matrix of the dorsal striatum. The mosaic configurations of tyrosine hydroxylase, but not calcium-binding protein immunoreactivity, were similar in dorsal and ventral striatal regions. Substance P and leucine-enkephalin were not distributed homogeneously; distinct types and the prevalence of patches of substance P and leucine-enkephalin immunoreactivity distinguish the dorsal striatum from the ventral striatum and distinguish the caudate nucleus from the putamen. In the dorsal striatum, substance P and leucine-enkephalin patches consist of dense islands of immunoreactive neurons and puncta or clusters of immunoreactive neurons marginated by a dense rim of terminal-like puncta; the matrix was also enriched in leucine-enkephalin-immunoreactive neurons but contained less substance P-immunoreactive neurons. Patches were more prominent in the caudate nucleus than in the putamen. In the caudate, compartments low in tyrosine hydroxylase and calcium-binding protein immunoreactivities corresponded to cytologically identified cell islands and to patches enriched in substance P and leucine-enkephalin. These patches had a discrete infrastructure based on the location of substance P and leucine-enkephalin-immunoreactive neurons and terminals. In the ventral striatum, patches that showed low levels of substance P and leucine-enkephalin immunoreactivities were embedded in a matrix rich in immunoreactive cell bodies, fibers and terminals. In the accumbens, regions showing little tyrosine hydroxylase were in spatial register with patches low in substance P and leucine-enkephalin. Neurotensin- and somatostatin-immunoreactive neurons or processes were also compartmentally organized, particularly in the ventral striatum. Neurotensin-immunoreactive neurons were present predominantly in the nucleus accumbens but not in the dorsal striatum. Some regions enriched in neurotensin immunoreactivity were spatially registered with zones low in tyrosine hydroxylase, substance P and zones enriched in leucine-enkephalin. Areas enriched in somatostatin-immunoreactive processes overlapped with both tyrosine hydroxylase-rich and -poor regions in the ventral striatum. Our results show that the chemoarchitectonic topography of the striatal mosaic is different in the dorsal and ventral striatum of rhesus monkey and that the compartmental organization of some neurotransmitters/neuropeptides in the ventral striatum is variable and not as easily divisible into conventional patch and matrix regions as in the dorsal striatum.(ABSTRACT TRUNCATED AT 400 WORDS)     

Two types of projection neurons in human striatum: Peculiarities of their somatodendritic structure in ventral and dorsal striatum

The somatodendritic structure of projection neurons was morphometrically examined in the nucleus accumbens of human brain. In contrast to reticular neurons, spiny neurons of the nucleus accumbens and dorsal striatum have different somatodendritic structure. In both parts of the striatum, reticular neurons were NADPH-diaphorase-positive. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 6, pp. 604–608, June, 2006     

Electrical stimulation of dorsal and ventral striatum differentially alters the copulatory behavior of male rats

Sexual behavior is a natural reward that activates striatal dopaminergic (DA) circuits, and dopamine exerts a facilitative influence on copulation. Electrical stimulation of the striatum has been shown to be rewarding, but its effect on male sexual behavior display has not been established. The objective of the present work was to assess the effects of low- and high-frequency electrical stimulation of the dorsal and ventral striatum on male rat sexual behavior expression. To this aim, copulatory activity of sexually experienced male rats was recorded during electrical stimulation of the nucleus accumbens (NAcc) or caudate-putamen (CP), at each stimulation frequency, before and after sexual exhaustion. Results showed that electrical stimulation of the NAcc at both frequencies increased the number of ejaculations that male rats were able to show in a 30-min period. By contrast, stimulation delivered to the CP inhibited sexual behavior by slowing its display. Each effect was more pronounced at low than at high stimulation frequencies. In the same rats, once sexually exhausted, electrical stimulation of these brain areas did not reverse the sexual behavior inhibition that characterizes the sexual exhaustion state. It is concluded that dorsal and ventral striatal DA brain regions exert opposite influences on copulatory behavior expression of sexually experienced male rats. Also, that the facilitative effect of NAcc electrical stimulation on sexual activity, with the stimulation parameters used, cannot surmount the sexual behavior inhibition resulting from copulation to satiation.     

Both dorsal and ventral hippocampus contribute to spatial learning in Long-Evans rats

The hippocampus (HPC) may be functionally heterogeneous in supporting spatial learning in rats. Thus, dorsal but not ventral HPC lesions have been reported to impair acquisition in the Morris water task which consists of finding a submerged platform in a pool filled with opaque water. To further investigate the functional differences between dorsal and ventral HPC regions, we used a one-trial matching to position water task in which the submerged platform occupied a different position during each session. This task is very sensitive to HPC damage. The results show that either dorsal or ventral HPC NMDA lesions disrupt the rapid acquisition of new place information. The acquisition deficit diminishes with training in both lesion groups. The data thus suggest that the entire HPC axis is involved in acquisition of spatial information.     

Dopamine high-affinity transport site topography in rat brain: major differences between dorsal and ventral striatum

Investigations were conducted to determine the topography of the high-affinity dopamine uptake process within the rat striatum. [3H]Dopamine uptake into crude synaptosomes prepared from micropunch samples was found to be two- to three-fold higher in dorsal caudate-putamen relative to nucleus accumbens septi. In contrast, the concentrations of dopamine in the two regions were equivalent. The recognition site associated with high-affinity dopamine uptake was labeled using [3H]mazindol, and the binding of this ligand was also found to be two- to three-fold higher in homogenates from dorsal caudate-putamen samples relative to nucleus accumbens septi. Regional differences in uptake of [3H]dopamine or binding of [3H]mazindol were shown to be due to variations in Vmax or Bmax, not to differences in apparent affinity. Autoradiography of [3H]mazindol binding in rat striatum revealed a decreasing density of the site along the dorsal-to-ventral axis, with the highest binding occurring in the dorsolateral caudate-putamen, lower binding in the ventral caudate-putamen, and lowest levels in the septal pole of the nucleus accumbens septi. Quantification showed that the extent of this gradient was two-fold. Further autoradiographic studies revealed less striatal heterogeneity in the pattern of binding of [3H]ketanserin, another radioligand associated with the striatal dopaminergic innervation but not linked to the dopamine uptake process of the plasma membrane. The findings suggest that the dopaminergic fibers of the ventral striatum, especially the medial nucleus accumbens septi, may be relatively lacking in their capacity for dopamine uptake following its release. This organization may result in regional differences in the time-course of of extraneuronal dopamine following transmitter release and may render the dopamine-containing terminals of the ventral striatum less susceptible to the degenerative influences of neurotoxins that are incorporated by the high-affinity dopamine uptake process.     

Participation cholinergic systems of the dorsal and ventral striatum in the training of rats to avoidance in a T-maze

Influence of activation of cholinergic systems of the dorsal (Caudate-Putamen) and ventral (Accumbens) striatum on the process of the training of rats to active avoidance in a T-maze was investigated in experiments on 60 male Sprague-Dawley rats. The results, obtained on one and the same behavioral model (active avoidance in a T-maze), suggest the presence of particular features of the participation of the cholinergic systems of the dorsal and ventral striatum in the regulation of motor behavior. Thus, a one-time administration of carbacholine (Cbch, 0.03 μg) increases the level of correct responses on the first and succeeding days of the training of the rats to active avoidance, when microinjections are made into the right Accumbens, and also induces a significant increase in the level of correct realizations on the second and third days of training when microinjections are made in the left Accumbens, and at the same time, similar influences on the Caudate-Putamen do not induce any significant changes in the behavior of the animals during training in a T-maze. The changes in the locomotor activity according to collective data in the various groups of rats exhibited a generally complex character: from experiment to experiment, the level of the locomotor activity of the animals decreased in the majority of cases, but microinjections of the substances did not alter the locomotor activity of the animals in any of the groups. However, the degree of change in the level of locomotor activity in the group of rats with microinjections into the Accumbens (in this investigation, the degree of increase) very markedly depended on the localization of the cannula. The greatest effect was obtained in the lateral segment of this nucleus; this confirms the functional heterogeneity of this fairly small nuclear structure. This study was carried out with the financial support of the Russian Basic Research Fund (project No. 93-04-21061). I. P. Pavlov Institute of Physiology, Russian Academy of Sciences. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Saint Petersburg. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 45, No. 2, pp. 297–304, March–April, 1995.     

Role of the cholinergic systems of the dorsal and ventral striatum of the rat brain in controlling learned movements

Comparative studies were performed of the effects of injections of a cholinergic agonist (carbachol) and antagonist (scopolamine) into the ventral and dorsal striatum on the performance of a learned movement involving prolonged maintenance of extension of the forelimb in rats. Doses of carbachol (0.03–3.00 μg) into the ventral striatum were accompanied by increases in the numbers of movements with prolonged maintenance of extension with application of pressure against an obstacle, with a simultaneous decrease in the percentage of rapid nonreinforced movements (by an average of 18.8%). Injections into the dorsal striatum disrupted slow movements which were not reinforced during training, on a background of stable performance of the learned reflex. Doses of scopolamine (0.3–3.0 μg) into both the dorsal and ventral parts of the striatum produced increases (by 22.7±8.2% and 68.9±14.3%) in the numbers of rapid nonreinforced movements typical of the repertoire of untrained animals. These data led to the suggestion that the cholinergic system of the ventral striatum is involved in the maintenance of forelimb muscle tone in rats during the performance of movements in which pressure is applied to an obstacle. The cholinergic system of the dorsal striatum does not have this property, but plays a significant role in the process of learning new sensory-controlled movements. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry; Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 1-2, pp. 83–89, January–February, 1997.     

Participation of cholinergic systems of the dorsal and ventral striatum in the training of rats to avoidance in a T-maze

Neuroscience and Behavioral Physiology -     

Participation of the cholinergic system of the dorsal and ventral striatum in the regulation of various forms of defense behavior

Laboratory of Physiology of Higher Nervous activity, I. P. Pavlov Institute of Physiology, Russian Academy Sciences, Saint Petersburg. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 80, No. 1, pp. 139–1 January, 1994.     

Direct comparison of neural systems mediating conscious and unconscious skill learning

Procedural learning, such as perceptual-motor sequence learning, has been suggested to be an obligatory consequence of practiced performance and to reflect adaptive plasticity in the neural systems mediating performance. Prior neuroimaging studies, however, have found that sequence learning accompanied with awareness (declarative learning) of the sequence activates entirely different brain regions than learning without awareness of the sequence (procedural learning). Functional neuroimaging was used to assess whether declarative sequence learning prevents procedural learning in the brain. Awareness of the sequence was controlled by changing the color of the stimuli to match or differ from the color used for random sequences. This allowed direct comparison of brain activation associated with procedural and declarative memory for an identical sequence. Activation occurred in a common neural network whether initial learning had occurred with or without awareness of the sequence, and whether subjects were aware or not aware of the sequence during performance. There was widespread additional activation associated with awareness of the sequence. This supports the view that some types of unconscious procedural learning occurs in the brain whether or not it is accompanied by conscious declarative knowledge.     

Differential neural correlates of reciprocal activation and cocontraction control in dorsal and ventral premotor cortices

Efficient control of reciprocal activation and cocontraction of the muscles are critical to perform skillful actions with suitable force and impedance. However, it remains unclear how the brain controls force and impedance while recruiting the same set of muscles as actuators. Does control take place at the single muscle level leading to force and impedance, or are there higher-order centers dedicated to controlling force and impedance? We addressed this question using functional MRI during voluntary isometric wrist contractions with online electromyogram feedback. Comparison of the brain activity between the conditions requiring control of either wrist torque or cocontraction demonstrates that blood oxygen level-dependent activity in the caudo-dorsal premotor cortex (PMd) correlates well with torque, whereas the activity in the ventral premotor cortex (PMv) correlates well with the level of cocontraction. This suggests distinct roles of the PMd and PMv in the voluntary control of reciprocal activation and cocontraction of muscles, respectively.     

Transsynaptic induction of c-fos in basal forebrain,diencephalic and midbrain neurons following AMPA-induced activation of the dorsal and ventral striatum

In these experiments, induction of the immediate early gene c-fos following excitation of striatal neurons has been used to investigate the organization of the ventral and dorsal striatopallidal systems and the relationship between striatal neurons and cholinergic neurons of the nucleus basalis magnocellularis (of Meynert, nbM). The results demonstrate that FOS immunoreactivity (ir) can be detected in ventral and dorsal striatal neurons following infusions of the non-N-methyl-d-aspartic acid (NMDA) glutamate receptor agonist -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). This activation and increased expression of FOS in striatal neurons was itself associated with the sustained appearance of FOS-ir in neurons of the ipsilateral ventral and dorsal pallidum, subthalamic nucleus and some thalamic nuclei. Infusions of AMPA into the ventral striatum (VS), but not the dorsal striatum (DS), also resulted in the appearance of FOS-ir in a proportion (17%) of the cholinergic neurons of the nbM. By combining the retrograde transport of Fluoro-Gold with FOS immunocytochemistry, it was also possible to demonstrate that approximately 46% and 58% of the pallidal neurons containing FOS-ir after infusions of AMPA into the VS or DS, respectively, directly project to the subthalamic nucleus. Taken together, these observations suggest that visualizing the protein product of transsynaptic c-fos induction provides an effective way to study the topographic and transsynaptic, within-system consequences of striatal activation.     

Attentional functions in dorsal and ventral simultanagnosia

Whole report of brief letter arrays is used to analyse basic attentional deficits in dorsal and ventral variants of simultanagnosia. Using Bundesen's Theory of Visual Attention (TVA), a number of previous theoretical suggestions are formalised and tested, including primary deficit in processing more than one display element, attentional stickiness, foveal bias, and global weakness of the visual representation. Interestingly, data from two cases, one dorsal and one ventral, show little true deficit in simultaneous perception, or selective deficit in those TVA parameters (short-term memory capacity, attentional weighting) specifically associated with multi-element displays. Instead there is a general reduction in speed of visual processing (processing rate in TVA), effective even for a single display element but compounded when two or more elements compete.     

Encoding of action history in the rat ventral striatum

In a dynamic environment, animals need to update information about the rewards expected from their alternative actions continually to make optimal choices for its survival. Because the reward resulting from a given action can be substantially delayed, the process of linking a reward to its causative action would be facilitated by memory signals related to the animal's previous actions. Although the ventral striatum has been proposed to play a key role in updating the information about the rewards expected from specific actions, it is not known whether the signals related to previous actions exist in the ventral striatum. In the present study, we recorded neuronal ensemble activity in the rat ventral striatum during a visual discrimination task and investigated whether neuronal activity in the ventral striatum encoded signals related to animal's previous actions. The results show that many neurons modulated their activity according to the animal's goal choice in the previous trial, indicating that memory signals for previous actions are available in the ventral striatum. In contrast, few neurons conveyed signals on impending goal choice of the animal, suggesting the absence of decision signals in the ventral striatum. Memory signals for previous actions might contribute to the process of updating the estimates of rewards expected from alternative actions in the ventral striatum.