Physiology and pathophysiology of the basal ganglia—thalamo—cortical networks

doi:10.1016/S1353-8020(08)70045-2

Parkinsonism & Related Disorders

Volume 13, Supplement 3, 2007, Pages S437-S439

https://doi.org/10.1016/S1353-8020(08)70045-2 Get rights and content

Abstract

Low-frequency resting tremor is one of the cardinal signs of Parkinson's disease (PD) and occurs also in some of its animal models. Current physiological studies and models of the basal ganglia indicate that changes of discharge pattern and synchronization of basal ganglia neurons rather than modification in their discharge rate are crucial to the pathophysiology of PD. However, parkinsonian tremor is not strictly correlated with the synchronous oscillations in the basal ganglia networks. We therefore suggest that abnormal basal ganglia output enforces abnormal thalamo–cortical processing leading to akinesia, the main negative symptom of Parkinson's disease. The parkinsonian positive motor signs, such as tremor and rigidity, most likely evolve as a downstream compensatory mechanism.

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Cited by (29)

The Pedunculopontine Tegmental Nucleus is not Important for Breathing Impairments Observed in a Parkinson's Disease Model
2023, Neuroscience
Parkinson’s disease (PD) is a motor disorder resulting from degeneration of dopaminergic neurons of substantia nigra pars compacta (SNpc), with classical and non-classical symptoms such as respiratory instability. An important region for breathing control, the Pedunculopontine Tegmental Nucleus (PPTg), is composed of cholinergic, glutamatergic, and GABAergic neurons. We hypothesize that degenerated PPTg neurons in a PD model contribute to the blunted respiratory activity. Adult mice (40 males and 29 females) that express the fluorescent green protein in cholinergic, glutamatergic or GABAergic cells were used (Chat-cre Ai6, Vglut₂-cre Ai6 and Vgat-cre Ai6) and received bilateral intrastriatal injections of vehicle or 6-hydroxydopamine (6-OHDA). Ten days later, the animals were exposed to hypercapnia or hypoxia to activate PPTg neurons. Vglut₂-cre Ai6 animals also received retrograde tracer injections (cholera toxin b) into the retrotrapezoid nucleus (RTN) or preBötzinger Complex (preBötC) and anterograde tracer injections (AAV-mCherry) into the SNpc. In 6-OHDA-injected mice, there is a 77% reduction in the number of dopaminergic neurons in SNpc without changing the number of neurons in the PPTg. Hypercapnia activated fewer Vglut₂ neurons in PD, and hypoxia did not activate PPTg neurons. PPTg neurons do not input RTN or preBötC regions but receive projections from SNpc. Although our results did not show a reduction in the number of glutamatergic neurons in PPTg, we observed a reduction in the number of neurons activated by hypercapnia in the PD animal model, suggesting that PPTg may participate in the hypercapnia ventilatory response.
A comparison of the relationship between manual dexterity and postural control in young and older individuals with Parkinson's disease
2020, Journal of Clinical Neuroscience
Citation Excerpt :
The increase is approximately 1–2% especially in individuals over 65 years of age [4]. Basal ganglia play an important role in the pathogenesis of the disease [5]. Dopaminergic neurons in the basal ganglia that regulate movement activation [6] degenerate by apoptosis in PD [7].
The motor symptoms of Parkinson's disease (PD) cause deterioration in manual dexterity. This deterioration affects independence in activities of daily living negatively. The loss of postural control, which occurs more frequently with disease progression, restricts physical functions and reduces mobility in patients with PD. Impaired postural control may affect distal mobility of an individual. The aim of this study was to investigate postural control and manual dexterity in individuals ≤ 65 and >65 years with PD and analyze the relationship between these variables according to age. Sixty-six individuals with PD participated in the study. The participants were categorized according to age (n = 29 for 65 years of age or younger and n = 37 for older). Manual dexterity (Dominant and Non-dominant hand) was assessed by the Nine Hole Peg Test (NHPT). Postural control was evaluated by the Limit of Stability Test (LoS) using a computerized balance measuring instrument. There was no statistically significant difference between the age groups on the combined dependent variables after controlling for disability, gender, weight, and height; F(7, 54) = 0.804, p = 0.587. Only LoS-Maximum Excursion was higher in the individuals ≤ 65 years (p = 0.035). Significant correlations were found between NHPT-Dominant and LoS-Reaction Time, LoS-Maximum Excursion; NHPT-Non-dominant and LoS-Reaction Time, LoS-Endpoint Excursion, LoS-Maximum Excursion in the older group (p < 0.05). There was no difference manual dexterity and postural control according to age except for LoS-Maximum Excursion. LoS-Maximum Excursion was higher in the young group. The manual dexterity was associated with postural control in individuals over 65 years of age with PD; however, not associated in younger individuals.
Selective basal ganglia vulnerability to energy deprivation: Experimental and clinical evidences
2018, Progress in Neurobiology
Citation Excerpt :
The basal ganglia (BG) include several sub-cortical brain structures pivotal for motor control, motor learning, cognitive function and reward (Alexander, 1986; Calabresi et al., 2014; Rosin et al., 2007).
The basal ganglia (BG) include structures pivotal for motor and cognitive functions. Such structures are affected in neurodegenerative disorders and toxic or ischemic insults. The peculiar vulnerability of BG to toxic and ischemic damage has been the focus of preclinical research for all over the last century. This comprehensive review collects all evidences supporting a specific susceptibility of BG to energy deprivation, highlighting the pathways through which neuronal survival is jeopardized, and the consequent clinical correlates. In particular, we addressed intrinsic and extrinsic factors participating in BG neuronal vulnerability. The terminal blood supply, the main extrinsic factor, is crucial to the low threshold for hypoxic hazard. Specific, the lack of anastomoses between second and third order branches represents the frailty of an archaic terminal network, unable to guarantee collateral supply and resistance to oxygen deprivation. In addition, BG neurons survival is jeopardized by several intrinsic molecular factors. Among them, the subunit composition of ionotropic and metabotropic glutamate receptors, the impairment of mitochondria, the deficit in neurotransmitter clearance, the poor control of intracellular calcium homeostasis and the glutamatergic-dopaminergic pro-excitotoxic interplay, all play a significant role. Intrinsic and extrinsic factors represent two faces of the same coin, producing excitotoxic damage and poor ability to deal with energy deprivation. The clinical correlates of BG vulnerability are represented by ischemic lesions, such as striatocapsular infarcts and lacunar infarcts, and local toxic-induced damage, mainly associated with energy production impairment, due to carbon monoxide, cyanide and manganese.
Basal ganglia output to the thalamus: Still a paradox
2013, Trends in Neurosciences
Citation Excerpt :
We have suggested that excitation and inhibition are temporally matched in the thalamus, and this may ensure control of spike timing [83,84], In singing birds, thalamic spikes are time-locked to pallidal spikes with submillisecond precision [24], and in mammals BG neurons exhibit temporally precise spikes in relation to brief population bursts that occur at specific times in behavioral tasks [85,86]. In addition, BG disease is associated with abnormal oscillations and network synchrony [53,54,87,88], but the link between abnormal timing and motor dysfunction remains unclear. Future studies are required to test by what mechanism spike timing could be important.
The basal ganglia (BG)-recipient thalamus controls motor output but it remains unclear how its activity is regulated. Several studies report that thalamic activation occurs via disinhibition during pauses in the firing of inhibitory pallidal inputs from the BG. Other studies indicate that thalamic spiking is triggered by pallidal inputs via post-inhibitory ‘rebound’ calcium spikes. Finally excitatory cortical inputs can drive thalamic activity, which becomes entrained, or time-locked, to pallidal spikes. We present a unifying framework where these seemingly distinct results arise from a continuum of thalamic firing ‘modes’ controlled by excitatory inputs. We provide a mechanistic explanation for paradoxical pallidothalamic coactivations observed during behavior that raises new questions about what information is integrated in the thalamus to control behavior.
Spontaneous synchronized burst firing of subthalamic nucleus neurons in rat brain slices measured on multi-electrode arrays
2012, Neuroscience Research
Citation Excerpt :
The basal ganglia are part of a closed loop connecting all cortical areas sequentially through the striatum, pallidum, and thalamus with the frontal cortex, which then projects downstream to the spinal level (Rosin et al., 2007).
The current study presents an organotypic rat midbrain slice culture that served as a consistent and informative framework, where the STN neurons and their interconnectivity were closely examined with respect to electrophysiological and pharmacological properties. From multi-electrode array recordings, it was found that the majority of STN neurons spontaneously fired in bursts rather than tonically under control conditions, and the neural activity between pairs of burst-firing STN neurons was tightly correlated. This spontaneous synchronized burst firing was also affected by a glutamate receptor antagonist, yet unaffected by a GABA receptor antagonist. Moreover, even when the STN was isolated from all its known external inputs, spontaneous synchronized burst firing was still observed under control conditions and consistently switched to tonic firing following the application of a glutamate receptor antagonist. Therefore, the results indicated the existence of glutamatergic projections to the STN in the slice preparation, and these excitatory synaptic connections appeared to originate from axon collaterals within the STN rather than other basal ganglia nuclei. It could be concluded that the STN neurons and their interconnectivity are essential requirements in the rat brain slice preparation to produce spontaneous synchronized burst firing.
Nonlinear temporal organization of neuronal discharge in the basal ganglia of Parkinson's disease patients
2010, Experimental Neurology
Previous electrophysiological studies of the basal ganglia in Parkinson's disease (PD) patients have utilized linear analyses in time-or-frequency domains to characterize neuronal discharge patterns. However, these measures do not fully describe the non-linear features of discharge rates and oscillatory activities of basal ganglia neurons.
In this original research, we investigate whether non-linear temporal organizations exist in the inter-spike interval series of neurons recorded in the globus pallidus or the subthalamic nucleus in PD patients undergoing surgery for the implantation of deep brain stimulating electrodes.
Our data indicate that in approximately 80% of globus pallidus and subthalamic neurons, the raw inter-spike interval sequences have lower entropy values than those observed after shuffling of the original series. This is the first report establishing non-linear temporal organization as a common feature of neuronal discharge in the basal ganglia of PD patients.

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View full text

Physiology and pathophysiology of the basal ganglia—thalamo—cortical networks

Abstract

Neurosci Res

Trends Neurosci

Deep brain stimulation for Parkinson's disease

Mov Disord

The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies

Proc Natl Acad Sci USA

Synaptic organisation of the basal ganglia

J Anat

Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism

Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism

Brain Res