Selective innervation of neostriatal interneurons by a subclass of neuron in the globus pallidus of the rat

A subpopulation of neurons in the globus pallidus projects to the neostriatum, which is the major recipient of afferent information to the basal ganglia. Given the moderate nature of this projection, we hypothesized that the pallidostriatal projection might exert indirect but powerful control over principal neuron activity by targeting interneurons, which comprise only a small percentage of neostriatal neurons. This was tested by the juxtacellular labeling and recording of pallidal neurons in combination with immunolabeling of postsynaptic neurons. In addition to innervating the subthalamic nucleus and output nuclei, 6 of 23 labeled pallidal neurons projected to the neostriatum. Both the firing characteristics and the extent of the axonal arborization in the neostriatum were variable. However, light and electron microscopic analysis of five pallidostriatal neurons revealed that each neuron selectively innervated neostriatal interneurons. A large proportion of the boutons of an individual axon (19-66%) made contact with parvalbumin-immunoreactive interneurons. An individual parvalbumin-immunoreactive neuron (n = 27) was apposed on average by 6.7 boutons (SD = 6.1) from a single pallidal axon (n = 2). Individual pallidostriatal boutons typically possessed more than one symmetrical synaptic specialization. In addition, 3-32% of boutons of axons from four of five pallidal neurons contacted nitric oxide synthase-immunoreactive neurons. Descending collaterals of pallidostriatal neurons were also found to make synaptic contact with dopaminergic and GABAergic neurons of the substantia nigra. These data imply that during periods of cortical activation, individual pallidal neurons may influence the activity of GABAergic interneurons of the neostriatum (which are involved in feed-forward inhibition and synchronization of principle neuron activity) while simultaneously patterning neuronal activity in basal ganglia downstream of the neostriatum.     

Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene

Glutamatergic synaptic potentials induced by micromolar concentrations of the potassium conductance blocker 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in the presence of 10 microM bicuculline (BIC). These synaptic potentials originate from neostriatal cortical and thalamic afferents and were completely blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric acid (2-APV). Their inter-event time intervals could be fitted to exponential distributions, suggesting that they are induced randomly. Their amplitude distributions had most counts around 1 mV and fewer counts with values up to 5 mV. Since input resistance of the recorded neurons is about 40 M omega, the amplitudes agree to quantal size measurements in mammalian central neurons. The action of a D2 agonist, quinpirole, was studied on the frequency of these events. Mean amplitude of synaptic potentials was preserved in the presence of 2-10 microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic potentials was reduced in 35% of cases. The effect was blocked by the D2 antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing threshold did not change during quinpirole effect, suggesting a presynaptic site of action for quinpirole in some but not all glutamatergic afferents that make contact on a single cell. The present experiments show that dopaminergic presynaptic modulation of glutamatergic transmission in the neostriatum does not affect all stimulated afferents, suggesting that it is selective towards some of them. This may control the quality and quantity of afferent flow upon neostriatal neurons.     

Automatic imitation of biomechanically possible and impossible actions: Effects of priming movements versus goals.

Recent behavioral, neuroimaging, and neurophysiological research suggests a common representational code mediating the observation and execution of actions; yet, the nature of this representational code is not well understood. The authors address this question by investigating (a) whether this observation-execution matching system (or mirror system) codes both the constituent movements of an action as well as its goal and (b) how such sensitivity is influenced by top-down effects of instructions. The authors tested the automatic imitation of observed finger actions while manipulating whether the movements were biomechanically possible or impossible, but holding the goal constant. When no mention was made of this difference (Experiment 1), comparable automatic imitation was elicited from possible and impossible actions, suggesting that the actions had been coded at the level of the goal. When attention was drawn to this difference (Experiment 2), however, only possible movements elicited automatic imitation. This sensitivity was specific to imitation, not affecting spatial stimulus-response compatibility (Experiment 3). These results suggest that automatic imitation is modulated by top-down influences, coding actions in terms of both movements and goals depending on the focus of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mosaic pattern of gliosis in the neostriatum of a North American man with craniocervical dystonia and parkinsonism

We present the case of a 51-year-old patient with a 31-year history of psychiatric symptoms, craniocervical dystonia, bulbar dysfunction, and parkinsonism. His dystonic movements included blepharospasm, jaw opening and lingual dystonia, and spasmodic retrocollis. Psychiatric symptoms included psychosis and depression, with onset years before the movement disorder. After his death by aspiration, examination of his brain revealed abnormalities limited to the neostriatum. Staining of brain sections, including Holzer, glial fibrillary acidic protein, and immunohistochemical stain for calbindin D28k, revealed the presence of a mosaic pattern of gliosis with neuronal loss (sparing large neurons) within this region. The islands of tissue between stands of gliosis had a normal appearance. This patient represents only the fourth case (and first North American born) with a mosaic pattern of gliosis in the neostriatum. The clinical and pathologic features were similar in all four cases except that our patient was the first with prominent psychiatric symptoms and a more stable, less progressive course. Mosaicism has been described in the X-linked Filipino disorder Lubag. Occurrence in non-Filipino patients, such as ours, suggest that either Lubag can develop in non-Filipino families or that mosaicism is a nonspecific pathologic finding in some patients with idiopathic dystonia. Finally, our case reports the notion that craniocervical dystonia may result from neostriatal dysfunction.     

Distinct frontal regions for processing sentence syntax and story grammar

Time is a fundamental dimension of cognition. It is expressed in the sequential ordering of individual elements in a wide variety of activities such as language, motor control or in the broader domain of long range goal-directed actions. Several studies have shown the importance of the frontal lobes in sequencing information. The question addressed in this study is whether this brain region hosts a single supramodal sequence processor, or whether separate mechanisms are required for different kinds of temporally organised knowledge structures such as syntax and action knowledge. Here we show that so-called agrammatic patients, with lesions in Broca's area, ordered word groups correctly to form a logical sequence of actions but they were severely impaired when similar word groups had to be ordered as a syntactically well-formed sentence. The opposite performance was observed in patients with dorsolateral prefrontal lesions, that is, while their syntactic processing was intact at the sentence level, they demonstrated a pronounced deficit in producing temporally coherent sequences of actions. Anatomical reconstruction of lesions from brain scans revealed that the sentence and action grammar deficits involved distinct, non-overlapping sites within the frontal lobes. Finally, in a third group of patients whose lesions encompassed both Broca's area and the prefrontal cortex, the two types of deficits were found. We conclude that sequence processing is specific to knowledge domains and involves different networks within the frontal lobes.     

Patterns of excitatory and inhibitory synaptic transmission in the rat neostriatum as revealed by 4-AP

1. Synaptic potentials induced by 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in an in vitro slice preparation. EC50 for this 4-AP action was approximately 120 microM. The threshold for activation of synaptic potentials was 5 microM. 2. 4-AP-induced synaptic potentials appeared stochastically. Most were blocked by 1 microM tetrodotoxin or 400 microM Cd2+. Therefore they reflect a release of neurotransmitters dependent on both Ca2+ entry to the terminals and action potential firing. 3. Bicuculline (BIC) (< or = 10 microM), a gamma-aminobuturic acid-A (GABAA) antagonist, blocked about half of the 4-AP-induced synaptic potentials. This suggests that intrinsic inhibitory connections within the neostriatum are activated by 4-AP administration. 4. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; < or = 10 microM) plus D-2-amino-5-phosphonovaleric acid (D-APV; < or = 100 microM) blocked most of the BIC-resistant 4-AP-induced synaptic potentials. This suggests that 4-AP induced release of glutamate (GLU) from extrinsic glutamatergic afferents. As most glutamatergic afferents are extrinsic, these afferents then would be able to fire spikes and release transmitter for several hours after they are cut from their somata. 5. If CNQX plus D-APV were administered before BIC, neostriatal neurons responded in different ways. In one half of the neurons, all induced synaptic potentials were blocked. This suggests that most GABAergic intrinsic connections between neostriatal neurons are activated indirectly by 4-AP. 4-AP would first activate extrinsic glutamatergic afferents and these in turn would activate GABAergic intrinsic neurons and connections. 6. In the remaining half of the recorded neurons, administration of CNQX plus D-APV blocked most, but not all of the 4-AP-induced synaptic potentials. The synaptic potentials that remained had a characteristic pattern: they were high amplitude, rhythmic, bursts of synaptic potentials. They were blocked by BIC (5 microM) but not by mecamylamine (> 10 microM). This suggests that these bursts of synaptic potentials were GABAergic and generated by intrinsic neurons. Therefore these neurons would not innervate all neostriatal neurons equally but just a subset of them. 7. Records from an identified aspiny neostriatal interneuron, obtained from the same preparation, are shown. This interneuron fired in bursts and its morphologically and physiologically similar to the recently described, fast spiking, parvalbumin immunoreactive, GABAergic, aspiny interneuron is functional in the slice preparation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reward prediction in primate basal ganglia and frontal cortex

Reward information is processed in a limited number of brain structures, including fronto-basal ganglia systems. Dopamine neurons respond phasically to primary rewards and reward-predicting stimuli depending on reward unpredictability but without discriminating between rewards. These responses reflect 'errors' in the prediction of rewards in correspondence to learning theories and thus may constitute teaching signals for appetitive learning. Neurons in the striatum (caudate, putamen, ventral striatum) code reward predictions in a different manner. They are activated during several seconds when animals expect predicted rewards. During learning, these activations occur initially in rewarded and unrewarded trials and become subsequently restricted to rewarded trials. This occurs in parallel with the adaptation of reward expectations by the animals, as inferred from their behavioral reactions. Neurons in orbitofrontal cortex respond differentially to stimuli predicting different liquid rewards, without coding spatial or visual features. Thus, different structures process reward information processed in different ways. Whereas dopamine neurons emit a reward teaching signal without indicating the specific reward, striatal neurons adapt expectation activity to new reward situations, and orbitofrontal neurons process the specific nature of rewards. These reward signals need to cooperate in order for reward information to be used for learning and maintaining approach behavior.     

Movement sequence-related activity reflecting numerical order of components in supplementary and presupplementary motor areas

The supplementary motor area (SMA) and presupplementary motor areas (pre-SMA) have been implicated in movement sequencing, and neurons in SMA have been shown to encode what might be termed the relational order among sequence components (e.g., movement X followed by movement Y). To determine whether other aspects of movement sequencing might also be encoded by SMA or pre-SMA neurons, we analyzed task-related activity recorded from both areas in conjunction with a sequencing task that dissociated the numerical order of components (e.g., movement X as the 2nd component, irrespective of which movements precede or follow X). Sequences were constructed from eight component movements, each characterized by three spatial variables (origin, direction, and endpoint). Task-related activity recorded from 56 SMA and 63 pre-SMA neurons was categorized according to both the epoch (delay, reaction time, and movement time) and the spatial variable or component movement with which it was associated. All but one instance of task-related activity was selective for one of the spatial variables (SV-selective) rather than for any of the component movements themselves. Of 110 instances of SV-selective activity in SMA, 43 (39%) showed significant effects of numerical order. The corresponding incidence in pre-SMA, 82 (71%) of 116, was substantially higher (P < 0.00001). No effects of numerical order were evident among the hand paths, movement times, or electromyographic activity associated with task performance. We concluded that neurons in SMA and pre-SMA may encode the numerical order of components, at least for sequences that are distinguished mainly by that aspect of component ordering.     

Functional differentiation within the neostriatum of the rat using electrical (blocking) stimulation during discrimination learning.

16 male albino rats, 8 with bipolar electrodes implanted bilaterally in the anterodorsal head of the caudate-putamen and 8 with similar electrodes in the posteroventral caudate-putamen, learned a spatial and a form discrimination task and their reversals while receiving "continuous" stimulation. Ss receiving stimulation to the anterodorsal caudate-putamen were impaired on spatial reversal learning compared with the posteroventral group. On form discrimination reversal the posteroventral group was impaired compared with the anterodorsal group. This dissociation appears to be related to the particular cortical neostriatal projection system for the region stimulated and to demonstrate a behavioral differentiation in rat neostriatum comparable with that observed in the monkey. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overview of periodontal clinical trials utilizing anti-infective or host modulating agents

In ants, antennal movements support the stimulus perception of olfactory and mechanosensory sensilla, most of which are located on the distal part of the antenna. In addition, sensory hair plates, campaniform sensilla, and Janet's organ provide the ant with proprioceptive information about the position, velocity, and acceleration of their antennae. We describe the morphology of these proprioceptors and their afferent neurons with special reference to the trap-jaw ant genus Odontomachus. All these sensory neurons terminate in the dorsal lobe, the part of the brain that also contains antennal motor neurons and that controls antennal movements. Neurons originating from campaniform sensilla and Janet's organ send additional collaterals into the subesophageal ganglion. Particularly fast antennal movements occur during protective withdrawal of the antenna. Under natural conditions, antennal retraction in Odontomachus always precedes the rapid mandible strike. We have found no indication of monosynaptic coupling between the antennal proprioceptive afferents and the trigger motor neurons that release the mandible strike. Instead, complex neuronal interactions in the involved neuromeres are more likely to control the timing of the two reflexes. The normal behavioral sequence of antennal retraction can be reversed by artificially releasing the mandible strike earlier than normal. The significance of fast antennal reflexes and of proprioceptive control is discussed.     

Coding controlled and triggered cursor movements as action effects: Influences on the auditory Simon effect for wheel-rotation responses.

Four experiments investigated influences of irrelevant action effects on response selection in Simon tasks for which tone pitch was relevant and location irrelevant, and responses were clockwise- counterclockwise wheel rotations. When the wheel controlled left-right movement of a cursor in a direction opposite an instructed left-right hand-movement goal, the Simon effect was reduced. When the wheel was held at the bottom, this reduction was due to some participants coding responses relative to the cursor and others relative to the hands. However, when the wheel was held at the top, it was due to participants integrating cursor movements with hand movements as a single action concept. In contrast, a cursor triggered by the wheel movement showed little influence on the Simon effect, even when contiguity and contingency with the wheel movements were high. Experience with the controlled cursor in a prior trial block or between trials established a causal relation that enabled participants to code the triggered cursor as belonging to the action concept and thus reduce the Simon effect. Multiple factors determine the influence of an irrelevant action effect on performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MR findings of primary central nervous system lymphoma in a child. A case report

Huntington's disease is an autosomal dominant, inherited disorder that results in progressive degeneration of the basal ganglia (especially the neostriatal caudate nucleus and putamen) and other forebrain structures and is associated with a clinical profile of movement, cognitive and psychiatric impairments for which there is at present no effective therapy. Neuropathological, neurochemical and behavioral features of the disease can all be reproduced in experimental animals by local injection of excitotoxic or metabolic toxins into the neostriatum. All these features of the disease can be alleviated, at least in rats, by transplantation of embryonic striatal tissue into the degenerated striatum, which was the basis for commencing the first clinical trials of striatal transplantation in Huntington's patients. However, although rat striatal xenografts may temporarily reduce apomorphine-induced dyskinesias in monkeys, there has been no demonstration that allograft techniques that work well in rats translate effectively to the much larger differentiated striatum of primates. Here we demonstrate good survival, differentiation and integration of striatal allografts in the primate neostriatum, and recovery in a test of skilled motor performance. Long-term graft survival in primates indicates probable success for clinical transplants in Huntington's disease; in addition, our data suggest that graft placement has a direct influence on the pattern and extent of functional recovery.     

Visual "closed-loop" and "open-loop" characteristics of voluntary movement in patients with Parkinsonism and intention tremor

Normal voluntary movements are considered to be of two kinds, or to involve two components, (i) a ballistic or "open-loop" type, which are preprogrammed and executed without reference to current sensory information and (ii) a corrective or "closed-loop" type, whose course or termination are regulated by such information. In a previous paper it was suggested that Parkinsonism disrupted the first kind of movement, but intention tremor did not. In the present paper three experiments designed to test this hypothesis are described. Subjects were tested on an acquisition-tracking task using an oscilloscope display and joystick control, and measurements were made of the duration, velocity and error of their initial movements to acquire the target. Parkinsonian movements were found to be considerably different from normal in that (a) most movements by this group lasted longer than the reaction time for their initiation, as if including some secondary correction in their execution, (b) the rate of movement was not varied for different amplitudes (so keeping the duration fairly constant) as in normal subjects, but rather movements of all amplitudes were made at a constant slow rate, so that duration increased markedly with the larger steps, (c) error increased disproportionately as the velocity of movement increased; in particular any movements completed in one reaction time or less tended to be wildly inaccurate, (d) removing either the target or the response marker from the screen at the beginning of a movement had a significant effect, making it shorter in duration and smaller in amplitude than those usually produced with both markers visible all the time. Parkinsonian subjects showed no improvement in performance with repeated attempts at one movement over a whole sequence, so their deficit appears to be stable even after practice on a known fixed task. These results are interpreted as supporting the hypothesis that Parkinsonism interferes with the generation of accurate ballistic action which are characteristic of normal skilled movement. Tremor subjects in general resembled normal control subjects in their initial acquistion movements, but their accuracy was less with the larger steps.     

Measurement of neuronal surface area using high-voltage electron microscope tomography

High-voltage electron microscopy (HVEM) and axial tomography were used to reconstruct the three-dimensional structure of dendrites of intracellularly stained neostriatal spiny neurons. Neurons were stained using iontophoretic injection of horseradish peroxidase from an intracellular micropipet. Thick sections were cut on a vibratome, reacted with diaminobenzidine, and embedded in plastic. High-voltage electron microscopy was used to obtain high-resolution images of neuronal processes in 2- to 3-micron plastic sections cut from those blocks. Series of high-voltage electron micrographs were taken at 2 degrees increments of specimen tilt over a range of at least +/- 60 degrees, and three-dimensional reconstructions were generated from the series using an R-weighted backprojection method. An interactive procedure was used to draw the dendritic profiles from slices through the reconstructed volume and to measure volumes and surface areas of the dendrites. Values obtained in this manner matched previous findings using reconstruction from serial thin sections. The HVEM-tomography method offers an alternative to the serial-thin-section method for the quantitative analysis of neuronal shape.     

Shared motor error for multiple eye movements

Most natural actions are accomplished with a seamless combination of individual movements. Such coordination poses a problem: How does the motor system orchestrate multiple movements to produce a single goal-directed action? The results from current experiments suggest one possible solution. Oculomotor neurons in the superior colliculus of a primate responded to mismatches between eye and target positions, even when the animal made two different types of eye movements. This neuronal activity therefore does not appear to convey a command for a specific type of eye movement but instead encodes an error signal that could be used by multiple movements. The use of shared inputs is one possible strategy for ensuring that different movements share a common goal.     

Coding of intention in the posterior parietal cortex

To look at or reach for what we see, spatial information from the visual system must be transformed into a motor plan. The posterior parietal cortex (PPC) is well placed to perform this function, because it lies between visual areas, which encode spatial information, and motor cortical areas. The PPC contains several subdivisions, which are generally conceived as high-order sensory areas. Neurons in area 7a and the lateral intraparietal area fire before and during visually guided saccades. Other neurons in areas 7a and 5 are active before and during visually guided arm movements. These areas are also active during memory tasks in which the animal remembers the location of a target for hundreds of milliseconds before making an eye or arm movement. Such activity could reflect either visual attention or the intention to make movements. This question is difficult to resolve, because even if the animal maintains fixation while directing attention to a peripheral location, the observed neuronal activity could reflect movements that are planned but not executed. To address this, we recorded from the PPC while monkeys planned either reaches or saccades to a single remembered location. We now report that, for most neurons, activity before the movement depended on the type of movement being planned. We conclude that PPC contains signals related to what the animal intends to do.     

The neuropsychology of 3-D space

The neuropsychological literature on 3-D spatial interactions is integrated using a model of 4 major behavioral realms: (a) peripersonal (visuomotor operations in near-body space), (b) focal extrapersonal (visual search and object recognition), (c) action extrapersonal (orienting in topographically defined space), and (d) ambient extrapersonal (orienting in earth-fixed space). Each is associated with a distinct cortical network: dorsolateral peripersonal, predominantly ventrolateral focal-extrapersonal, predominantly ventromedial action-extrapersonal, and predominantly dorsomedial ambient-extrapersonal systems. Interactions in 3-D space are also regulated neurochemically with dopaminergic and cholinergic excitation associated with extrapersonal activation and noradrenergic and serotonergic excitation associated with peripersonal activation. This model can help explain the 3-D imbalances in prominant neuropsychological disorders.     

Activity of common marmosets (Callithrix jacchus) in limited spaces: Hand movement characteristics.

The increasing popularity of marmoset monkeys (Callithrix jacchus) in anatomical, behavioral, and electrophysiological studies has called for a detailed analysis of their natural behavior within limited spaces. In the present study, the authors analyzed hand movements during horizontal and vertical progressions in a cylinder. The trajectory of each hand covered the entire cylinder floor during horizontal progressions and the entire cylinder wall during vertical progressions. Different marmosets have different patterns of hand movement. The average maximum angle of hand movements for all marmosets during horizontal and vertical progressions oscillates, although the average over time is constant and similar for both hands, whereas head movements during horizontal progressions become smaller with successive progressions. Another observed difference between rats and monkeys was in the size of head and hand movements at the beginning of each experimental session. During the 1st horizontal progression, all marmosets moved their heads to a greater extent than their hands. This sequential head and hand movement is referred as bistable behavior. The bistable pattern of motor behavior, which was also observed in successive progressions, may be derived from an inherent fear of predators or exploratory interest of a novel environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analyzing family interaction: Taking time into account.

Recent advances in hardware and software have made the coding and analyzing of family interaction an easier task. The availability of relatively inexpensive devices that preserve time as part of the record makes the coding of onset and offset times of a variety of behavioral events feasible. Such data can be represented as timed-event sequences through Sequential Data Interchange Standard conventions and analyzed with a computer program designed for sequential analysis (the Generalized Sequential Querier). Coding units (entities coded, such as events) need not be the same as tallying units (entities counted, such as seconds); in fact, much can be gained by regarding them separately. Examples of both time-based reliability assessment and sequential analysis, and lagged event-based log-linear analysis, are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)