External Segment Of Globus Pallidus Research Articles

Striatal But Not Extrastriatal Dopamine Receptors Are Critical to Dopaminergic Motor Stimulation.

Dopamine (DA) is required for motor function in vertebrate animals including humans. The striatum, a key motor control center, receives a dense DA innervation and express high levels of DA D1 receptors (D1Rs) and D2 receptors (D2Rs). Other brain areas involved in motor function such as the globus pallidus external segment (GPe) and the substantia nigra pars reticulata (SNr) and the motor cortex (MC) also receive DA innervation and express DA receptors. Thus, the relative contribution of the striatal and extrastriatal DA systems to the motor function has been an important question critical for understanding the functional operation of the motor control circuits and also for therapeutic targeting. We have now experimentally addressed this question in the transcription factor Pitx3 null mutant (Pitx3Null) mice that have an autogenic and parkinsonian-like striatal DA denervation and hence supersensitive motor response to DA stimulation. Using DA agonist unilateral microinjection-induced rotation as a reliable readout of motor stimulation, our results show that L-dopa microinjection into the dorsal striatum (DS) induced 5–10 times more rotations than that induced by L-dopa microinjection into GPe and SNr, while L-dopa microinjection into the primary MC induced the least number of rotations. Furthermore, our results show that separate microinjection of the D1R-like agonist SKF81297 and the D2R-like agonist ropinirole into the DS each induced only modest numbers of rotation, whereas concurrent injection of the two agonists triggered more rotations than the sum of the rotations induced by each of these two agonists separately, indicating D1R–D2R synergy. These results suggest that the striatum, not GPe, SNr or MC, is the primary site for D1Rs and D2Rs to synergistically stimulate motor function in L-dopa treatment of Parkinson’s disease (PD). Our results also predict that non-selective, broad spectrum DA agonists activating both D1Rs and D2Rs are more efficacious anti-PD drugs than the current D2R agonists.

Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping.

The progression of Parkinson's disease (PD) seems to vary according to the disease stage, which greatly influences the management of PD patients. However, the underlying mechanism of progression in PD remains unclear. This study was designed to explore the progressive pattern of iron accumulation at different stages in PD patients. Sixty right-handed PD patients and 40 normal controls were recruited. According to the disease stage, 45 patients with Hoehn-Yahr stage ≤ 2.5 and 15 patients with Hoehn-Yahr stage ≥ 3 were grouped into early-stage PD (EPD) and late-stage PD (LPD) groups, respectively. The iron content in the cardinal subcortical nuclei covering the cerebrum, cerebellum and midbrain was measured using quantitative susceptibility mapping (QSM). The substantia nigra pars compacta (SNc) showed significantly increased QSM values in the EPD patients compared with the controls. In the LPD patients, while the SNc continued to show increased QSM values compared with the controls and EPD patients, the regions showing increased QSM values spread to include the substantia nigra pars reticulata (SNr), red nucleus (RN) and globus pallidus (GP). Our data also indicated that iron deposition was more significant in the GP internal segment (GPi) than in the GP external segment. No other regions showed significant changes in QSM values among the groups. Therefore, we were able to confirm a regionally progressive pattern of iron accumulation in the different stages of PD, indicating that iron deposition in the SNc is affected exclusively in the early stages of the disease, while the SNr, RN and GP, and particularly the GPi segment, become involved in advanced stages of the disease. This is a preliminary study providing objective evidence of the iron-related progression in PD. Copyright © 2016 John Wiley & Sons, Ltd.

Computational Models Describing Possible Mechanisms for Generation of Excessive Beta Oscillations in Parkinson's Disease.

In Parkinson’s disease, an increase in beta oscillations within the basal ganglia nuclei has been shown to be associated with difficulty in movement initiation. An important role in the generation of these oscillations is thought to be played by the motor cortex and by a network composed of the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe). Several alternative models have been proposed to describe the mechanisms for generation of the Parkinsonian beta oscillations. However, a recent experimental study of Tachibana and colleagues yielded results which are challenging for all published computational models of beta generation. That study investigated how the presence of beta oscillations in a primate model of Parkinson’s disease is affected by blocking different connections of the STN-GPe circuit. Due to a large number of experimental conditions, the study provides strong constraints that any mechanistic model of beta generation should satisfy. In this paper we present two models consistent with the data of Tachibana et al. The first model assumes that Parkinsonian beta oscillation are generated in the cortex and the STN-GPe circuits resonates at this frequency. The second model additionally assumes that the feedback from STN-GPe circuit to cortex is important for maintaining the oscillations in the network. Predictions are made about experimental evidence that is required to differentiate between the two models, both of which are able to reproduce firing rates, oscillation frequency and effects of lesions carried out by Tachibana and colleagues. Furthermore, an analysis of the models reveals how the amplitude and frequency of the generated oscillations depend on parameters.

Incremental stability of delayed neural fields: a unifying framework for endogenous and exogenous sources of pathological oscillations

Neural fields are integro-differential equations that have been extensively used to model spatiotemporal evolution of neocortical areas (see [1] for a detailed review). Time-delayed neural fields have also been a matter of investigation since they take into account axonal delays [2]. On the other hand, time-delay finite dimensional systems have been used in models of Parkinson's disease: delays have been shown to play a possible role in the generation of pathological neural oscillations linked to motor symptoms of Parkinson disease in a firing-rate model of basal ganglia [3,4]. Nonetheless, these models fail at rendering the spatial distribution of the neural activity of the populations involved. Two possible mechanisms for the onset of pathological oscillations in basal ganglia have been investigated in the literature. The first one, the endogenous mechanism, hypothesizes that dopamine depletion tends to increase the synaptic gains between the excitatory neurons of the subthalamic nucleus (STN) and the inhibitory neurons of the external segment of globus pallidus (GPe), thus generating an instability that translates into sustained oscillations. The second one, the exogenous mechanism, explains these oscillations onset by a diffusion of spontaneous oscillations from external structures (such as Striatum) to the GPe-STN network [5]. The main goal of this work is to deepen this analysis by providing theoretical conditions under which a network of time-delayed neural field equations is incrementally stable. We believe that incremental stability constitutes an instrumental framework to investigate both the mechanisms evoked above. Indeed, by considering constant inputs to the basal ganglia, incremental stability ensures convergence to a unique equilibrium configuration, thus ruling out the possibility of endogenous mechanism for oscillations onset. On the other hand, incremental stability guarantees entrainability to periodic inputs (meaning convergence to a T-periodic solution in response to any T-periodic input), and can thus be useful to unravel the mechanism of pathological diffusion from external structures in the exogenous scenario. Relying on the Razumikhin-Lyapunov approach here we derive these sufficient conditions for incremental stability of delayed neural fields. This theoretical framework thus complements the Krasovskii-Lyapunov approach already used in the literature to address the stability of delayed neural fields equations [6]. Simulations confirm our theoretical expectations and demonstrate that interconnected neural fields can exhibit sustained oscillations, according to either the endogenous or the exogenous mechanism, depending on the strength of the synaptic weights between the excitatory (STN) and the inhibitory (GPe) populations. The derived theoretical results thus seem to constitute a fertile ground for further investigations based on experimental data, to discriminate between the endogenous and the exogenous hypotheses for Parkinsonian sustained oscillations in the STN-GPe network.

Posttetanic enhancement of striato-pallidal synaptic transmission.

The striato (Str)-globus pallidus external segment (GPe) projection plays major roles in the control of neuronal activity in the basal ganglia under both normal and pathological conditions. The present study used rat brain slice preparations to characterize the enhancement of Str-GPe synapses observed after repetitive conditioning stimuli (CS) of Str with the whole cell patch-clamp recording technique. The results show that 1) the Str-GPe synapses have a posttetanic enhancement (PTE) mechanism, which is considered to be a combination of an augmentation and a posttetanic potentiation; 2) the degree of PTE observed in GPe neurons had a wide range and was positively correlated with a wide range of paired-pulse ratios assessed before application of CS; 3) a wide range of CS, from frequencies as low as 2 Hz with as few as 5 pulses to as high as 100 Hz with 100 pulses, could induce PTE; 4) the decay time constant of PTE was dependent on the strength of CS and was prolonged greatly, up to 120 s, when strong CS were applied; and 5) the level of postsynaptic Cl(-) became a limiting factor for the degree of PTE when strong CS were applied. These results imply that Str-GPe synapses transmit inhibitions in a nonlinear activity-weighted manner, which may be suited for scaling timing and force of repeated or sequential body movements. Other possible factors controlling the induction of PTE and functional implications are also discussed.

Structural differences in basal ganglia of elite running versus martial arts athletes: a diffusion tensor imaging study.

The aim of this study was to use diffusion tensor imaging (DTI) to characterize and compare microscopic differences in white matter integrity in the basal ganglia between elite professional athletes specializing in running and martial arts. Thirty-three young adults with sport-related skills as elite professional runners (n = 11) or elite professional martial artists (n = 11) were recruited and compared with non-athletic and healthy controls (n = 11). All participants underwent health- and skill-related physical fitness assessments. Fractional anisotropy (FA) and mean diffusivity (MD), the primary indices derived from DTI, were computed for five regions of interest in the bilateral basal ganglia, including the caudate nucleus, putamen, globus pallidus internal segment (GPi), globus pallidus external segment (GPe), and subthalamic nucleus. Results revealed that both athletic groups demonstrated better physical fitness indices compared with their control counterparts, with the running group exhibiting the highest cardiovascular fitness and the martial arts group exhibiting the highest muscular endurance and flexibility. With respect to the basal ganglia, both athletic groups showed significantly lower FA and marginally higher MD values in the GPi compared with the healthy control group. These findings suggest that professional sport or motor skill training is associated with changes in white matter integrity in specific regions of the basal ganglia, although these positive changes did not appear to depend on the type of sport-related motor skill being practiced.

Role of the indirect pathway of the basal ganglia in perceptual decision making.

The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed-accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease.

Direct and indirect pathways of the basal ganglia: opponents or collaborators?

Direct and indirect pathways of the basal ganglia: opponents or collaborators?

Two Types of Neurons in the Primate Globus Pallidus External Segment Play Distinct Roles in Antisaccade Generation.

The globus pallidus external segment (GPe) constitutes part of the indirect pathway of the basal ganglia. Because of inhibitory projections from the striatum, most GPe neurons are expected to reduce activity during movements. However, many GPe neurons in fact display increased activity. We previously found that both excitatory and inhibitory responses were modulated during antisaccades, when eyes were directed away from a visual stimulus. To elucidate the roles of these neurons during antisaccades, we examined neuronal activities as monkeys performed antisaccades, prosaccades, and NoGo tasks under 2 conditions. In the Deliberate condition, the task-rule was instructed by color of the fixation point, while in the Immediate condition, it was given by color of the target. Under both conditions, the increase-type neurons exhibited greater activity during antisaccades compared with the other tasks and neuronal activity negatively correlated with saccade latency. The decrease-type neurons also showed greater modulation during antisaccades but their activity was comparable between NoGo and antisaccade trials in the Immediate condition. These results suggest that the increase-type neurons might play a role in facilitating antisaccades, whereas the decrease-type neurons could mediate signals for reflexive saccade suppression. We propose that these GPe neurons are differently involved in basal ganglia pathways.

The response of the subthalamo-pallidal networks of the Basal Ganglia to oscillatory cortical input in Parkinson’s disease

Primary motor symptoms of Parkinson’s disease such as bradykinesia and rigidity are associated with increased oscillatory and synchronized activity in the beta frequency band (10-30Hz) throughout the cortical-basal ganglia-thalamic circuitry (see, for example, [1]). The origin of the pathological beta-band oscillations is not completely understood, however it appears that both cortical circuits (reviewed in [2]) as well as subthalamo-pallidal circuitry [3] in the basal ganglia contribute to the generation and expression of pathological rhythmicity. The objective of this study is to explore the oscillatory interactions between cortical and basal ganglia networks in parkinsonian patients and in computational models of Parkinson’s disease. Two types of data from were recorded from subjects with Parkinson’s disease during the implantation of deep brain stimulation electrodes. We performed microelectrode recordings of neuronal units and local field potentials from the subthalamic nucleus. We also recorded surface EEG from prefrontal and motor areas recorded simultaneously with the recordings in the subthalamic nucleus. The analysis of these data reveals complex patters of correlations between synchrony in cortical circuits (which can be studied noninvasively) and synchrony in the basal ganglia circuits (which requires invasive procedures for investigation). These results are used to guide the development of computational models to study how activity in the subthalamo-pallidal circuits can be entrained by the oscillatory cortical input. We used conductance-based models for the excitatory-inhibitory networks of neurons from the subthalamic nucleus and the external segment of Globus Pallidus [4,5] and subject them to a series of artificially-generated cortical inputs as well as to the input signals derived from the experimentally recorded EEG. The biologically-realistic temporal patterns of synchrony, which are generated by the subthalamo-pallidal model network [4] are observed in the networks under cortical inputs too (although for different parameter values). The patterns of responses of beta-band bursting in the model suggest that the experimentally observed beta-band synchronization in Parkinson’s disease may be promoted by the simultaneous action of both cortical and subthalamo-pallidal network mechanisms. This may explain why some theories explaining the origins of pathological beta-band activity in Parkinson’s disease suggest a cortical origin of pathological oscillations, while others suggest local, subthalamo-pallidal generation [1-3].

Morphologic changes of dendritic spines of striatal neurons in the levodopa‐induced dyskinesia model

Maladaptive plasticity at corticostriatal synapses plays an important role in the development of levodopa-induced dyskinesia. Recently, it has been shown that synaptic plasticity is closely linked to morphologic changes of dendritic spines. To evaluate morphologic changes of dendritic spines of two types of striatal medium spiny neurons, which project to the internal segment of globus pallidus or the external segment of globus pallidus, in the levodopa-induced dyskinesia model, we used 6-hydroxydopamine-lesioned rats chronically treated with levodopa. Dendritic spines were decreased and became enlarged in the direct pathway neurons of the model of levodopa-induced dyskinesia. The same levodopa treatment to normal rats, in which no dyskinesia was observed, also induced enlargement of dendritic spines, but not a decrease in density of spines in the direct pathway neurons. These results suggest that a loss and enlargement of dendritic spines in the direct pathway neurons plays important roles in the development of levodopa-induced dyskinesia.

Short-term plasticity shapes activity pattern-dependent striato-pallidal synaptic transmission

The cortico-striato (Str)-globus pallidus external segment (GPe) projection plays major roles in the control of neuronal activity in the basal ganglia under both normal and pathological conditions. The present study used rat brain-slice preparations to address our hypothesis that the gain of this disynaptic projection is dynamically controlled by activations of short-term plasticity mechanisms of Str-GPe synapses. The Str-GPe projection neurons fire with very different frequency and firing patterns in vivo depending on the condition of the animal. The results show that the Str-GPe synapses have very strong short-term enhancement mechanisms and that repetitive burst activation of the Str-GPe synapses, which mimic oscillatory burst firing of Str neurons, can sustain enhanced states of synaptic transmission for tens of seconds. The results reveal that the short-term enhancement of Str-GPe synapses contributes to the generation of pauses in the firing of GPe neurons and that signal transfer function in the Str-GPe projection is highly dependent on the firing pattern of Str neurons.

Globus Pallidus External Segment Neuron Classification in Freely Moving Rats: A Comparison to Primates

Globus Pallidus external segment (GPe) neurons are well-characterized in behaving primates. Based on their firing properties, these neurons are commonly divided into two distinct groups: high frequency pausers (HFP) and low frequency bursters (LFB). However, no such characterization has been made for behaving rats. The current study characterizes and categorizes extracellularly recorded GPe neurons in freely moving rats, and compares these results to those obtained by extracellular recordings in behaving primates using the same analysis methods. Analysis of our data recorded in rats revealed two distinct neuronal populations exhibiting firing-pattern characteristics that are similar to those obtained in primates. These characteristic firing patterns are conserved between species although the firing rate is significantly lower in rats than in primates. Significant differences in waveform duration and shape were insufficient to create a reliable waveform-based classification in either species. The firing pattern analogy may emphasize conserved processing properties over firing rate per-se. Given the similarity in GPe neuronal activity between human and non-human primates in different pathologies, our results encourage information transfer using complementary studies across species in the GPe to acquire a better understanding of the function of this nucleus in health and disease.

Striatopallidal neurons regulate motor activity through the response pattern in the external segment of globus pallidus and substantia nigra pars reticulata

Striatopallidal neurons regulate motor activity through the response pattern in the external segment of globus pallidus and substantia nigra pars reticulata

Cortical Stimulation Evokes Abnormal Responses in the Dopamine-Depleted Rat Basal Ganglia

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Saccade, search and orient – the neural control of saccadic eye movements

One of the most important functions of the brain is to guide our behavior through an ever-changing environment as our goals and desires fluctuate. One simple, yet elegant system for investigating how sensory information and goal-related information combine to control and coordinate efficient behavior is the guidance of saccadic eye movements. The brain relies heavily on visual input to guide and coordinate our complex actions, but it is impossible for our brain to simultaneously process every aspect of visual information present in real world scenes at any given moment. Instead, the retina has evolved a highly specialized fovea in the center where we have the highest visual acuity. Therefore, to analyze a visual scene optimally, the eyes reorient in complex sequences so that the high acuity fovea of the retina can be directed to specific objects of interest. These saccadic eye movements are interspersed with periods of active fixation during which the visual system performs a detailed analysis of an object that may pertain to our current goals. Alternating between the serial process of making saccades and the analytical process of active fixation is repeated several hundred thousand times per day and is critical for numerous behaviors like reading this issue of EJN, driving an automobile or negotiating a busy sidewalk. In the laboratory, saccadic behavior can be measured easily and accurately. Quantitative analysis of saccade behavior can also serve as an important tool to investigate brain disorders in a host of neurological and psychiatric disorders (Leigh & Zee, 2006). Over the past few decades, there has been a tremendous increase in our knowledge of the systems that contribute to the control of saccadic eye movements. There have been many recent and exciting advances. Anatomical, physiological, clinical and imaging studies have contributed to our extensive knowledge of the saccade control circuit (Fig. 1), which includes regions of the occipital, parietal and frontal cortex, basal ganglia, thalamus, superior colliculus, cerebellum, and brainstem reticular formation. Within each of these brain regions are multiple populations of neurons and subnuclei that perform critical operations to coordinate behavior. In addition to overt eye movements that explicitly orient the visual system, visual selection may also be directed covertly to different locations or objects without any movement of the eyes. For example, we have the ability to shift attention away from where we look without initiating a saccade. Both overt (move the eyes) and covert (only shift attention) orienting can be directed voluntarily to a specific location or object, or involuntarily ‘captured’ by an abrupt change in the visual environment (Posner, 1980; Theeuwes, 1991; Fecteau & Munoz, 2006). There is significant overlap in the brain areas that participate in overt and covert orienting, which include several components of the frontoparietal network and the superior colliculus. This special issue of EJN contains reviews and original articles by some of the leading experts in the fields of saccades and visual search. There have been many recent exciting advances in these fields that are captured in the contributions in this issue. The contributions focus on different brain areas but the content ranges from the sensory input to the motor output and everything in between (Fig. 1). There are several different state-of-the-art technologies employed including quantitative behavioral analysis, neurophysiology, neuroimaging, clinical investigation, transcranial magnetic stimulation and modeling.

Role of Striatum in the Pause and Burst Generation in the Globus Pallidus of 6-OHDA-Treated Rats

Electrophysiological studies in patients and animal models of Parkinson's disease (PD) often reported increased burst activity of neurons in the basal ganglia. Neurons in the globus pallidus external (GPe) segment in 6-hydroxydopamine (6-OHDA)-treated hemi-parkinsonian rats fire with strong bursts interrupted by pauses. The goal of this study was to evaluate the hypothesis that dopamine (DA)-depletion increases burst firings of striatal (Str) neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe and its projection sites. To evaluate this hypothesis, the unitary activity of Str and GPe was recorded from control and 6-OHDA-treated rats anesthetized with 0.5–1% isoflurane. The occurrence of pauses and bursts in the firings of GPe neurons was significantly higher in 6-OHDA than in normal rats. Muscimol injection into the Str of 6-OHDA rats increased average firing rate and greatly reduced the pauses and bursts in GPe. Recordings from Str revealed that most of the presumed projection neurons in control rats have very low spontaneous activity, and even the occasional neurons that did exhibit spontaneous burst firings did so with an average rate of less than 2 Hz. In DA-depleted Str, neurons having stronger bursts and a higher average firing rate were encountered more frequently. Juxtacellular labeling revealed that most of these neurons were medium spiny neurons projecting only to GPe. Injection of a behaviorally effective dose of methyl-l-DOPA into the Str of 6-OHDA rats significantly increased the average firing rate and decreased the number of pauses of GPe neurons. These data validate the hypothesis that DA-depletion increases burst firings of Str neurons projecting to the GPe and that the increased Str–GPe burst inputs play a significant role in the generation of pauses and bursts in GPe. These results suggest that treatment to reduce burst Str–GPe inhibitory inputs may help to restore some PD disabilities.

Poincare return mapping for models of elliptic neurons

Event Abstract Back to Event Poincare return mapping for models of elliptic neurons Jeremy Wojcik1* and Andrey Shilnikov1 1 Georgia State University, Department of Mathematics and Statistics and the Neuroscience Institute, United States We propose a novel computer assisted method for the effective construction and accurate examination of families of Poincaré return mappings for voltage maxima in models of elliptic bursting neurons. Such busters are adequately described by dynamical systems with two characteristic time scales: slow and fast. A feature of a slow-fast dynamical model is that its solutions stay close to the so-called slow motion manifolds, comprised of equilibria and limit cycles of its fast subsystem. In the context of neurodynamics they are respectively called quiescent and tonic spiking equilibria. We reveal the topology of the manifolds in the phase space of an elliptic neuron model to define the Poincaré mappings for oscillatory dynamics of the fast membrane potential. The algorithms discussed allow us to create a full family of Poincare mappings to get insight into driving forces on the dynamics of a model in question over an entire parameter range. Of special interests are these mappings for nonlocal bifurcations at transitions between states of the model. This includes mechanisms of transitions between tonic spiking and bursting, between quiescence and tonic spiking, bifurcations of bursting, the emergence of various mixed mode oscillations, and their interactions with bursting and quiescence etc. The examination of nonlocal bifurcation at these transitions is accomplished through reduction of the multidimensional model to a one-dimensional voltage next amplitude mapping: T: Vn ?Vn+1. Such mappings allow us to identify and study bifurcations and complex dynamics of the model at such transitions. We note that the reduction to next amplitude mappings for maximal values of oscillatory voltage alone is highly advantageous as the behavior of any neuron model are manifest through the evolution of accumulative voltage dynamics which can only be accessed in experimental studies in most cases. We examine the mathematical Fitzhugh-Nagumo-Rinzel model, a bursting modification of the classical Hodgkin-Huxley model, as well as the Terman-Rubin model for the external segment of globus pallidus. We begin by creation of the respective slow motion manifolds through parameter continuation techniques. Next we are then able to extrapolate a set of maxima's, for each limit cycle of the manifold, to be used as initial conditions for the solution set for a given parameter. We then find the next maxima for the set of initial conditions creating a next amplitude map. Varying the parameter yields a family of next amplitude maps that allow for the identification of periodic and chaotic attractors, as well system repellers and homoclinic solutions that globally organize the dynamics of the model. We are then able to predict and/or identify the mechanisms for state transitions in the models, before the actual transition. Conference: 2010 South East Nerve Net (SENN) and Georgia/South Carolina Neuroscience Consortium (GASCNC) conferences, Atlanta , United States, 5 Mar - 7 Mar, 2010. Presentation Type: Poster Presentation Topic: Posters Citation: Wojcik J and Shilnikov A (2010). Poincare return mapping for models of elliptic neurons. Front. Neurosci. Conference Abstract: 2010 South East Nerve Net (SENN) and Georgia/South Carolina Neuroscience Consortium (GASCNC) conferences. doi: 10.3389/conf.fnins.2010.04.00088 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Mar 2010; Published Online: 18 Mar 2010. * Correspondence: Jeremy Wojcik, Georgia State University, Department of Mathematics and Statistics and the Neuroscience Institute, Atlanta, United States, jwojcik1@gsu.edu Login Required This action requires you to be registered with Frontiers and logged in. 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Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey

Deep brain stimulation (DBS), a surgical therapy for advanced Parkinson's disease (PD), is known to change neuronal activity patterns in the pallidothalamic circuit. Whether these effects translate to the motor cortex and, if so, how they might modulate the functional responses of individual neurons in primary motor cortex remains uncertain. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey was implanted with a DBS lead spanning internal and external segments of globus pallidus. During therapeutic stimulation (135 Hz) for rigidity and bradykinesia, neurons in primary motor cortex (M1) exhibited an inhibitory phase-locking (2–5 ms) to the stimulus, an overall decrease in mean discharge rate, and an increase in response specificity to passive limb movement. Sub-therapeutic DBS (30 Hz) still produced entrainment to the stimulation, but the mean discharge rate and specificity to movement were not changed. Lower stimulation intensities (at 135 Hz), which no longer improved motor symptoms, had little effect on M1 activity. These findings suggest that DBS improves parkinsonian motor symptoms by inducing global changes in firing pattern and rate along the pallido-thalamocortical sensorimotor circuit.

Mean-field modeling of the basal ganglia-thalamocortical system. I: Firing rates in healthy and parkinsonian states

Parkinsonism leads to various electrophysiological changes in the basal ganglia-thalamocortical system (BGTCS), often including elevated discharge rates of the subthalamic nucleus (STN) and the output nuclei, and reduced activity of the globus pallidus external (GPe) segment. These rate changes have been explained qualitatively in terms of the direct/indirect pathway model, involving projections of distinct striatal populations to the output nuclei and GPe. Although these populations partly overlap, evidence suggests dopamine depletion differentially affects cortico-striato-pallidal connection strengths to the two pallidal segments. Dopamine loss may also decrease the striatal signal-to-noise ratio, reducing both corticostriatal coupling and striatal firing thresholds. Additionally, nigrostriatal degeneration may cause secondary changes including weakened lateral inhibition in the GPe, and mesocortical dopamine loss may decrease intracortical excitation and especially inhibition. Here a mean-field model of the BGTCS is presented with structure and parameter estimates closely based on physiology and anatomy. Changes in model rates due to the possible effects of dopamine loss listed above are compared with experiment. Our results suggest that a stronger indirect pathway, possibly combined with a weakened direct pathway, is compatible with empirical evidence. However, altered corticostriatal connection strengths are probably not solely responsible for substantially increased STN activity often found. A lower STN firing threshold, weaker intracortical inhibition, and stronger striato-GPe inhibition help explain the relatively large increase in STN rate. Reduced GPe–GPe inhibition and a lower GPe firing threshold can account for the comparatively small decrease in GPe rate frequently observed. Changes in cortex, GPe, and STN help normalize the cortical rate, also in accord with experiments. The model integrates the basal ganglia into a unified framework along with an existing thalamocortical model that already accounts for a wide range of electrophysiological phenomena. A companion paper discusses the dynamics and oscillations of this combined system.