Ganglia Nuclei Research Articles

Intrinsic timescales across the basal ganglia

Recent studies have shown that temporal stability of the neuronal activity over time can be estimated by the structure of the spike-count autocorrelation of neuronal populations. This estimation, called the intrinsic timescale, has been computed for several cortical areas and can be used to propose a cortical hierarchy reflecting a scale of temporal receptive windows between areas. In this study, we performed an autocorrelation analysis on neuronal populations of three basal ganglia (BG) nuclei, including the striatum and the subthalamic nucleus (STN), the input structures of the BG, and the external globus pallidus (GPe). The analysis was performed during the baseline period of a motivational visuomotor task in which monkeys had to apply different amounts of force to receive different amounts of reward. We found that the striatum and the STN have longer intrinsic timescales than the GPe. Moreover, our results allow for the placement of these subcortical structures within the already-defined scale of cortical temporal receptive windows. Estimates of intrinsic timescales are important in adding further constraints in the development of computational models of the complex dynamics among these nuclei and throughout cortico-BG-thalamo-cortical loops.

Study on the Regulation Effect of Optogenetic Technology on LFP of the Basal Ganglia Nucleus in Rotenone-Treated Rats.

Background Parkinson's disease (PD) is a common neurological degenerative disease that cannot be completely cured, although drugs can improve or alleviate its symptoms. Optogenetic technology, which stimulates or inhibits neurons with excellent spatial and temporal resolution, provides a new idea and approach for the precise treatment of Parkinson's disease. However, the neural mechanism of photogenetic regulation remains unclear. Objective In this paper, we want to study the nonlinear features of EEG signals in the striatum and globus pallidus through optogenetic stimulation of the substantia nigra compact part. Methods Rotenone was injected stereotactically into the substantia nigra compact area and ventral tegmental area of SD rats to construct rotenone-treated rats. Then, for the optogenetic manipulation, we injected adeno-associated virus expressing channelrhodopsin to stimulate the globus pallidus and the striatum with a 1 mW blue light and collected LFP signals before, during, and after light stimulation. Finally, the collected LFP signals were analyzed by using nonlinear dynamic algorithms. Results After observing the behavior and brain morphology, 16 models were finally determined to be successful. LFP results showed that approximate entropy and fractal dimension of rats in the control group were significantly greater than those in the experimental group after light treatment (p < 0.05). The LFP nonlinear features in the globus pallidus and striatum of rotenone-treated rats showed significant statistical differences before and after light stimulation (p < 0.05). Conclusion Optogenetic technology can regulate the characteristic value of LFP signals in rotenone-treated rats to a certain extent. Approximate entropy and fractal dimension algorithm can be used as an effective index to study LFP changes in rotenone-treated rats.

Investigating Optimal Echo Times for Quantitative Susceptibility Mapping of Basal Ganglia Nuclei in the Healthy Brain

Quantitative susceptibility mapping (QSM) technique had been used to measure the magnetic susceptibility of brain tissue in clinical practice. However, QSM presented echo-time (TE) dependence, and an appropriate number of echo-times (nTEs) for QSM became more important to obtain the reliable susceptibility value. The aim of the study was to explore the optimal nTEs for quantitative susceptibility mapping (QSM) measurements of basal ganglia nuclei in the healthy brain. 3D multi-echo enhanced gradient recalled echo T2 star weighted angiography (ESWAN) sequence was acquired on a 3.0T MR scanner for QSM analysis. Regions of interests (ROIs) were drawn along the margin of the head of the caudate nucleus (HCN), putamen (Pu) and globus pallidus (GP). The mean susceptibility value and standard deviation of the ROIs were derived from the pixels within each region. CV analysis demonstrated that TE6, TE8 and TE14 ESWAN sequences presented consistent lower CV value (< 1) for QSM measure of HCN, Pu and GP. ANOVA identified that susceptibility value showed no significant difference between TE6 and TE8 in HCN, Pu and GP (P > 0.05). ICC analysis demonstrated that the susceptibility value of TE6-TE8 had the highest ICC value as compared with TE6-TE14 and TE8-TE14 in HCN, Pu and GP. Combined with the timeefficiency of MRI scanning, TE6 sequence could not only provide the reliable QSM measurement but also short imaging time. The current study identified that the optimal nTEs of ESWAN were 6 TEs (2.9ms ~ 80.9ms) for QSM measurement of basal ganglia nuclei in the healthy brain.

Involvement of nNOS in the antinociceptive activity of melatonin in inflammatory pain at the level of sensory neurons.

The efficacy of melatonin as an analgesic agent has been well documented in animals and humans. However, the underlying mechanisms by which melatonin exerts antinociceptive effects on inflammatory pain are poorly understood. Here, we investigated the potential of melatonin to ameliorate inflammatory pain. In vitro, ND7/23 neurons were treated with capsaicin. We used PCR and Western blot analyses to detect the expression of neuronal nitric oxide synthase (nNOS) in response to melatonin. Orofacial inflammatory pain was induced by 4% formalin administration on the right whisker pad of Sprague Dawley (SD) rats. The analgesic effect of melatonin was evaluated using mechanical threshold analyses. The expression level of nNOS in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (Vc) neurons was assessed by RNAscope and immunohistochemistry. In vitro, capsaicin upregulated the expression of nNOS, which was dose-dependently reversed by melatonin pretreatment (p < 0.001). In a rat model of orofacial inflammatory pain, melatonin pretreatment significantly attenuated mechanical allodynia in both the acute and chronic phases (p < 0.05). Furthermore, melatonin decreased the formalin-evoked elevated nNOS mRNA and protein levels in the TG and Vc neurons in the acute and chronic phases (p < 0.05). Taken together, these results suggest that nNOS may play an active role in both peripheral and central processing of nociceptive information following orofacial inflammatory pain induction. The regulatory effect of melatonin on nNOS in inflammatory pain may have potential implications for the development of novel analgesic strategies.

Analysis of the Pathways of the Influences of the Dorsal Raphe Nucleus on the Basal Ganglia Based on the Topography of the Projections between Them

Axonal transport of retrograde markers was used to study the characteristics of the organization of the projection systems connecting different parts of the dorsal raphe nucleus (DRN) with functionally diverse segments of striopallidal structures. The possible pathways by which the DRN may modulate the structures of the morphofunctional system of the basal ganglia are detailed. The projections to the limbic segments of the input nuclei of the basal ganglia from the dorsal part of the DRN, which is innervated by limbic structures, found here are evidence that limbic information may be conducted via these pathways. Projections from all parts of the DRN are directed to the input nuclei of the basal ganglia but not to the functionally diverse segments of the pallidal nuclei. The overlap found in the entopeduncular nucleus of the terminal fields of neurons from all parts of the DRN receiving and sending functionally diverse information to and from the basal ganglia system is evidence for the possible interaction of this information in this nucleus. The importance of these data for creating models aiding our understanding of the functioning of the basal ganglia in health and disease is assessed.

The Herpes Simplex Virus 1 Deamidase Enhances Propagation but Is Dispensable for Retrograde Axonal Transport into the Nervous System.

Upon replication in mucosal epithelia and transmission to nerve endings, capsids of herpes simplex virus 1 (HSV-1) travel retrogradely within axons to peripheral ganglia, where life-long latent infections are established. A capsid-bound tegument protein, pUL37, is an essential effector of retrograde axonal transport and also houses a deamidase activity that antagonizes innate immune signaling. In this report, we examined whether the deamidase of HSV-1 pUL37 contributes to the neuroinvasive retrograde axonal transport mechanism. We conclude that neuroinvasion is enhanced by the deamidase, but the critical contribution of pUL37 to retrograde axonal transport functions independently of this activity.IMPORTANCE Herpes simplex virus 1 invades the nervous system by entering nerve endings and sustaining long-distance retrograde axonal transport to reach neuronal nuclei in ganglia of the peripheral nervous system. The incoming viral particle carries a deamidase activity on its surface that antagonizes antiviral responses. We examined the contribution of the deamidase to the hallmark neuroinvasive property of this virus.

Investigation of cochlear hair cells and the perception of ultrasound signals in guinea pigs

We established a specific ultrasound frequency-dependent model of cochlear injury using bone conduction ultrasounds in the inner ear of guinea pigs at 50 kHz and 83 kHz, to explore the effects of bone conduction ultrasound in the cochlea. To establish a unilateral cochlear damage model, the unilateral cochlea was destroyed. The control group consisted of 50 kHz and 83 kHz bone conduction ultrasounds in unaltered guinea pigs. In each group, cerebral blood oxygenation level dependent (BOLD) effects were determined by functional magnetic resonance imaging (fMRI). The cochlear outer hair cell motor protein, Prestin, and the microfilament protein, F-Actin, were detected. We found that bone conduction ultrasound irradiation at 50 kHz and 83 kHz on the guinea pig inner ear for six hours leads to hair cell damage. Furthermore, low frequency bone conduction ultrasound induces major damage to outer hair cells, while high frequency ultrasound damages both internal and external hair cells. fMRI analysis of cerebral BLOD effects revealed an affected cerebral cortex region of interest (ROI) of 4 and 2, respectively, for the normal control group at 50 kHz or 83 kHz, and 2 for the 83 kHz bone conduction ultrasound cochlear injury group, while 50 kHz bone conduction ultrasound failed to induce the cortical ROI within injury model. Results reveal that the spatial location of guinea pig cochlear hair cells determines coding function for lower ultrasound frequencies, and high frequency bone conduction ultrasound may affect the cochlear spiral ganglion or cranial nerve nucleus in bone conduction ultrasound periphery perception.

Fahr’s Disease Presenting with Manic Symptoms

Bilateral striopallidodentate calcinosis, commonly known as Fahr's disease, is a rare syndrome characterised by symmetrical calcification over the basal ganglion and dentate nucleus. No case of Fahr's disease with associated manic symptoms has been described in the literature to date. We report an unusual case of Fahr's Disease in a 18 year old unmarried male who presented to the emergency department of Universal College of Medical Sciences - Teaching Hospital, Nepal with symptoms of mania. Computed tomographic scan of the patient demonstrated extensive symmetrical calcification over the basal ganglia and dentate nuclei. No underlying cause for the bilateral calcification was found. This rare case of Fahr's disease, which has never been reported in Indian literature has been reported to highlight this unusual condition and its differentiation from the commoner Fahr's syndrome.

Skellam process with resetting: a neural spike train model.

This paper introduces the Skellam process with resetting. Resetting is a modification that accommodates the modeling of neural spike trains. We show this as a biologically plausible model, which codes the information content of neural spike trains with three, potentially, time-varying functions. We show that the interspike interval distribution under this model follows a mixture of gamma distributions, a flexible class covering a wide range of commonly used models. Through simulation studies and the analyses of connected retinal ganglion and lateral geniculate nucleus cells, we evaluate the performance of this model. Copyright © 2016 John Wiley & Sons, Ltd.

P182. Patterns of gait-related electrophysiological activity in the human subthalamic nucleus of patients with Parkinson’s disease

Problems during gait constitute a severe disability for patients with Parkinson’s disease (PD) and lead to significant limitations during their daily life, especially in later stages of the disease. The nuclei of the basal ganglia are crucial for important aspects of motor processes and are used as target areas for deep brain stimulation therapy of the motor symptoms associated with PD. Investigations of the (patho)-physiology of these structures during gait should therefore contribute to our understanding of the neuronal processes involved during normal movement and clarify if symptom-specific pathological neuronal activity can be characterized. For this purpose, we investigated the electric local field potentials of the subthalamic nucleus of 12 patients with PD recorded from deep brain stimulation electrodes during walking and during rest. Simultaneously, the movement of the patients was recorded with inertial sensor units and subsequently analyzed in parallel to the electrophysiological activity. In this way, gait patterns like normal walking or akinetic freezing epochs can be reconstructed and their specific neuronal activity can be described with the analysis of the electrophysiological recordings. Attenuation of oscillations in the beta frequency band (12–35 Hz) can be observed in patients without freezing epochs during normal walking as compared to rest. In contrast, patients with freezing epochs show an increase in lower beta frequency (12–22 Hz) amplitude during walking as compared to rest as well as freezing epochs themselves show increased lower beta frequency as compared to normal walking and rest. Both, patients with nearly regular gait and patients with akinetic epochs did show an increase in the gamma frequency band (35–90 Hz) during movement. Our results show that an increase of oscillations in the lower beta band is highly correlated with severe freezing epochs and might possibly play a causal role for akinesia in PD. Such a symptom-specific and characteristic electrophysiological fingerprint could be used as a kind of marker of pathological neuronal activity for the adjustment of the deep brain stimulation therapy in a closed-loop fashion.

Cognitive training in neurodegenerative diseases: a way to boost neuroprotective molecules?

Cognitive training in neurodegenerative diseases: a way to boost neuroprotective molecules?

Functional role of opponent, dopamine modulated D1/D2 plasticity in reinforcement learning

The basal ganglia network is thought to be involved in adaptation of organism's behavior when facing its positive and negative consequences, that is, in reinforcement learning. It has been hypothesized that dopamine (DA) modulated plasticity of synapses projecting from different cortical areas to the input nuclei of the basal ganglia, the striatum, plays a central role in this form of learning, being responsible for updating future outcome expectations and action preferences. In this scheme, DA transmission is considered to convey a prediction error signal that is generated if internal expectations do not match the outcomes observed after action execution. So far, there has been no satisfying model for what neural circuits computing this signal within the basal ganglia may look like, how this computation is performed and what is the mechanistic role of DA release in adapting the system towards optimal behavior in a given task. Aiming towards a model of a canonical circuit for learning task-conform behavior from both reward and punishment, we extended a previously introduced spiking actor-critic network model of the basal ganglia [1] to contain the segregation of both the dorsal (actor) and ventral (critic) striatum into populations of D1 and D2 medium spiny neurons (MSNs). This segregation allows explicit, separate representation of both positive and negative expected outcomes by the distinct populations in the ventral striatum. The positive and negative components of expected outcome were fed to dopamine (DA) neurons in SNc/VTA region, which compute and signal reward prediction error by DA release. Based on recent experimental work [2], DA level was assumed to modulate plasticity of D1 and D2 synapses in opposing way, inducing LTP on D1 and LTD on D2 synapses if being high and vice versa if being low. Crucially, this form of opponent plasticity implements temporal-difference (TD)-like update of both positive and negative outcome expectations separately and performs appropriate action selection adaptation. We implemented the network in the NEST simulator [3] using leaky integrate-and-fire spiking neurons and designed a battery of experiments involving application of reward and punishment in various grid world tasks. In each task, an agent had to explore the states and learn to maximize the total reward obtained. Number of states, magnitudes and delays of reward and punishment were manipulated across different tasks. We demonstrate that across the tasks the network can learn both to approach the delayed rewards while consequently avoiding punishments, the latter posing severe difficulties for the previous model without D1/D2 segregation [1]. Thus, the spiking neural network model highlights the functional role of D1/D2 MSN segregation within the striatum in implementing appropriate TD-like learning from both reward and punishment and explains necessity for opponent direction of DA-dependent plasticity found at synapses converging on distinct striatal MSN types. This modeling approach can be extended in the future work to study how abnormal D1/D2 plasticity may lead to a reorganization of the basal ganglia network towards pathological, dysfunctional states, like for instance those observed in Parkinson disease under condition of progressive dopamine depletion.

L‐dopa‐induced dyskinesias in unilateral 6‐hydroxydopamine‐lesioned rats are not modified by excitotoxic lesion of the entopeduncular nucleus and substantia nigra pars reticulata

l-Dopa-induced dyskinesias (LIDs) are a troublesome complication in Parkinson's disease after long-term therapy and a major reason for surgical treatment. LIDs are effectively eliminated by surgery. We aimed to reproduce such effect in the 6-hydroxydopamine (6-OHDA)-lesioned rat model. Single or combined lesions with quinolinic acid were caused in the entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr) on 6-hydroxydopamine (6-OHDA)-lesioned rats treated for 3 weeks with l-Dopa (6 mg/kg plus 15 mg/kg benserazide, i.p.). l-Dopa administration was continued for a further week following the lesion and abnormal involuntary movements (AIMs) scored at the end of treatment. Neither the individual lesions of the EP and SNr nor the combined lesions had any antidyskinetic effect nor decreased the total number of rotations. These results suggest that excitotoxic lesions of neurons bodies of the output nuclei of the basal ganglia, which destroy cell bodies and spare fibers of passage, do not induce a beneficial reduction of dyskinesias in contrast to thermolytic lesions in humans (which provokes a complete tissue destruction), thus supporting the possibility that other nuclei or systems might be involved in the antidyskinetic effect of pallidotomy.

Differences in parvalbumin and calbindin chemospecificity in the centers of the turtle ascending auditory pathway revealed by double immunofluorescence labeling

Using double immunofluorescence labeling, quantitative ratio between parvalbumin- and calbindin-containing neurons, neurons that co-localize both peptides, as well as the intensity of their immunoreactivities were studied in the brainstem, midbrain and forebrain auditory centers of two chelonian species, Testudo horsfieldi and Emys orbicularis. In the spiral ganglion and first-order cochlear nuclei, highly immunoreactive parvalbumin-containing neurons predominated, and almost all neurons in these nuclei also exhibited weak immunoreactivity to calbindin. The number of strongly calbindin-immunoreactive (-ir) cells increased in the second-order brainstem auditory centers (the laminar cochlear nucleus, superior olivary complex, lateral lemniscal nucleus), and co-localization with parvalbumin in some of them was observed. In the midbrain, a complementary distribution of parvalbumin and calbindin immunoreactivity was found: the central (core) region of the torus semicircularis showed strong parvalbumin immunoreactivity, while the laminar (belt) nucleus was strongly calbindin-ir. In the thalamic nucleus reuniens, almost complete topographic overlapping of the parvalbumin-ir and calbindin-ir neurons was shown in its dorsomedial region (core), with the intensity of immunoreactivity to calbindin being much higher than that to parvalbumin. The predominance of calbindin immunoreactivity in neurons of the dorsomedial region of the nucleus reuniens is correlated with the existence of the dense calbindin-ir terminal field in its projection area in the telencephalon. We conclude that the turtle auditory pathway is chemically heterogeneous with respect to calcium-binding proteins, the predominance of parvalbumin in the brainstem and midbrain centers giving way to that of calbindin in the forebrain centers; the portion of neurons co-localizing both peptides nonlinearly decreases from lower to higher order centers.

Localization and co-localization of the migraine triggers nNOS, PACAP and CGRP in trigeminal ganglion and trigeminal nucleus caudalis

Localization and co-localization of the migraine triggers nNOS, PACAP and CGRP in trigeminal ganglion and trigeminal nucleus caudalis

The effect of PACAP-38 and VIP on CGRP release in dura mater, trigeminal ganglion and trigeminal nucleus caudalis

The effect of PACAP-38 and VIP on CGRP release in dura mater, trigeminal ganglion and trigeminal nucleus caudalis

A quantitative comparison of basal ganglia neuronal activities of normal and Parkinson's disease model rats

The purpose of this study was to identify consistent characteristic changes of neuronal activity in basal ganglia (BG) nuclei associated with Parkinson's disease (PD) so that a reliable index of PD can be derived. A simple algorithm for automatic identification of firing patterns was devised as an essential tool to achieve this goal. A detailed quantitative analysis of firing patterns as well as firing rate was performed in three BG nuclei: the subthalamic nucleus (STN), the substantia nigra pars reticulate (SNpr), and the globus pallidus (GP). The results showed that the firing rate of STN neurons was not significantly altered in PD model rats. We also did not find a significant alteration in firing rates in the SNpr and GP between normal and PD model rats. In contrast, consistent changes of firing patterns were observed in all three BG nuclei in that the percentage of neurons with a regular firing pattern decreased whereas those with irregular, mixed, or burst patterns increased. This enables a simple algorithm based on burst detection and the shape of the interspike interval histogram to identify whether the neuronal activity is from normal or PD model rats.

Shaping corticostriatal connectivity with STDP

The striatum, the main input nucleus of the basal ganglia, is one of the major sites for learning and decision making. The striatum receives massive convergent inputs from the cortex. Task related cortical activity show weak pairwise correlations, thus, individual medium-sized spiny neurons (MSNs) in the striatum are very likely to receive correlated activity from the cortex. Surprisingly, although cortical neurons outnumber MSNs and each MSN receives around 10,000 cortical inputs, neighboring medium-sized spiny neurons (MSNs) in the striatum are not likely to share their presynaptic inputs [1]. This special arrangement of corticostriatal projections and their inputs is thought to be important to obtain a better signal representation in the striatum [2]. How does this specific anatomical structure of the corticostriatal projection come about? Corticostriatal synapses show a gamut of spike-time-dependent plasticity (STDP) rules which can influence the structure of these projections [3]. Therefore, here, we explored the functional consequences of different STDP rules in shaping the structure of the corticostriatal projections. Specifically, we studied how the synaptic connections change when a striatal neuron receives a mixture of correlated and uncorrelated synaptic input spikes. Because a neuron is more likely to elicit a spike in response to coincident inputs, the synapses receiving correlated inputs are expected to strengthen over time, whereas those receiving uncorrelated inputs are expected to undergo long-term depression, due to the depression-dominated features of the STDP rule. Furthermore, recurrent inhibition among MSNs implies that STDP would also organize corticostriatal projections such as to reduce the input correlations and sharing of presynaptic neurons among MSNs coupled with recurrent inhibitory synapses. The detailed structure of corticostriatal projections, therefore, depends on the intricate statistics of the cortical inputs, recurrent connectivity and activity within the striatum. In summary, here we show that standard STDP may explain the observed anatomical structure of the corticostriatal projections. Thus, an interplay of different corticostriatal STDP rules, together with the interactions in the network of MSNs and striatal interneurons, may encode signals from the cortex and modulate the activity of striatal neurons, in particular, the MSNs, which provide the striatal output to the downstream nuclei of the basal ganglia.

Human fronto-tectal and fronto-striatal-tectal pathways activate differently during anti-saccades

Almost all cortical areas in the vertebrate brain take part in recurrent connections through the subcortical basal ganglia (BG) nuclei, through parallel inhibitory and excitatory loops. It has been suggested that these circuits can modulate our reactions to external events such that appropriate reactions are chosen from many available options, thereby imposing volitional control over behavior. The saccade system is an excellent model system to study cortico-BG interactions. In this study two possible pathways were investigated that might regulate automaticity of eye movements in the human brain; the cortico-tectal pathway, running directly between the frontal eye fields (FEF) and superior colliculus (SC) and the cortico-striatal pathway from the FEF to the SC involving the caudate nucleus (CN) in the BG. In an event-related functional magnetic resonance imaging (fMRI) paradigm participants made pro- and anti-saccades. A diffusion tensor imaging (DTI) scan was made for reconstruction of white matter tracts between the FEF, CN and SC. DTI fiber tracts were used to divide both the left and right FEF into two sub-areas, projecting to either ipsilateral SC or CN. For each of these FEF zones an event-related fMRI timecourse was extracted. In general activity in the FEF was larger for anti-saccades. This increase in activity was lateralized with respect to anti-saccade direction in FEF zones connected to the SC but not for zones only connected to the CN. These findings suggest that activity along the contralateral FEF–SC projection is responsible for directly generating anti-saccades, whereas the pathway through the BG might merely have a gating function withholding or allowing a pro-saccade.

Induction of activating transcription factor 3 (ATF3) by peripheral nerve compression

Nuclear translocation of activating transcription factor 3 (ATF3), used as a marker for neuronal injury, was studied by immunocytochemistry in sensory neurons in dorsal root ganglia and locally along the sciatic nerve after severe chronic nerve compression in rats. In compressed nerves (application of a narrow silicone tube), ATF3 immunoreactivity was seen in the nucleus of sensory neurons and in Schwann cells below the compression at two and four weeks. Removal of the silicone tube (decompression) at two weeks did not affect the number of ATF3-positive cell nuclei in dorsal root ganglia. No ATF3 immunoreactivity was found in undamaged nerves on the other side. Functional variables (toe spreading and muscle force) were impaired at two weeks, with partial improvement at four weeks. Nerve compression induces nuclear translocation of ATF3, a transcription factor associated with survival and regeneration of sensory neurons. The response is related to duration of compression and partly correlated to function.