Somatosensory inputs to the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxidase study in the rat

doi:10.1016/0006-8993(88)90495-7

Brain Research

Volume 458, Issue 1, 16 August 1988, Pages 53-64

https://doi.org/10.1016/0006-8993(88)90495-7 Get rights and content

Abstract

Previous physiological studies have shown that neurons in the subthalamic nucleus (STN) respond to peripheral somatosensory stimulation. In an attempt to identify anatomical pathways that could mediate such responses, the possible existence of direct projections from somatosensory central territories to the STN was investigated in the rat with the aid of retrograde and anterograde horseradish peroxidase tracer techniques. Our main findings indicate the existence of a hitherto undescribed and relatively substantial direct projection from the primary somatosensory cortex to the ipsilateral STN. The projection appears to originate chiefly from neurons in layer Vb of the rostral half of this cortical area and to terminate basically in the dorsolateral district of the STN. Moreover, our data are compatible with the existence of very sparse direct projections from the spinal trigeminal and dorsal column nuclei to the contralateral STN, but the evidence on this point is hardly conclusive.

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Additionally, medium-latency responses were not observed with pallidal and thalamic stimulation (Bhanpuri et al., 2014; Devergnas and Wichmann, 2011; Limousin et al., 1998; Miocinovic et al., 2018; Ni et al., 2018; Tisch et al., 2008), with one notable exception (Walker et al., 2012b). The absence of medium-latency eCR for pallidal stimulation indicates that they are likely to represent HDP activation (Miocinovic et al., 2018), which would also be consistent with the broad cortical distribution of medium-latency eCR (Canteras et al., 1988; Miocinovic et al., 2018; Nambu et al., 1997). Most electrocorticography studies were able to detect three separate medium-latency eCR (Ashby et al., 2001; Chen et al., 2020; Miocinovic et al., 2018) (Table 1).
The subthalamic nucleus (STN) receives input from various cortical areas via hyperdirect pathway (HDP) which bypasses the basal-ganglia loop. Recently, the HDP has gained increasing interest, because of its relevance for STN deep brain stimulation (DBS). To understand the HDP's role cortical responses evoked by STN-DBS have been investigated. These responses have short (<2 ms), medium (2–15 ms), and long (20–70 ms) latencies. Medium-latency responses are supposed to represent antidromic cortical activations via HDP. Together with long-latency responses the medium responses can potentially be used as biomarker of DBS efficacy as well as side effects. We here propose that the activation sequence of the cortical evoked responses can be conceptualized as high frequency oscillations (HFO) for signal analysis. HFO might therefore serve as marker for antidromic activation. Using existing knowledge on HFO recordings, this approach allows data analyses and physiological modeling to advance the pathophysiological understanding of cortical DBS-evoked high-frequency activity.
Human subthalamic oscillatory dynamics following somatosensory stimulation
2018, Clinical Neurophysiology
Electrical median nerve somatosensory stimulation leads to a distinct modulation of cortical oscillations. Initial high frequency and gamma augmentation, as well as modulation of beta and alpha oscillations have been reported. We aimed at investigating the involvement of the subthalamic nucleus in somatosensory processing by means of local field potential recordings, since recordings during passive movements and peripheral somatosensory stimulation have suggested a prominent role.
Recordings of subthalamic neuronal activity following median nerve stimulation in 11 Parkinson’s disease patients were performed. Time-frequency analysis from 1 to 500 Hz was averaged and analyzed.
Several oscillatory components in response to somatosensory stimulation were revealed in the time-frequency analysis: (I) prolonged increase in alpha band power, followed by attenuation; (II) initial suppression of power followed by a subsequent rebound in the beta band; (III) early broad-frequency increase in gamma band power; (IV) and sustained increase of 160 Hz frequency oscillations throughout the trial.
These results further corroborate the involvement of the subthalamic nucleus in somatosensory processing.
The present results not only support the notion of somatosensory processing in the subthalamic nucleus. Moreover, an improvement of somatosensory processing during subthalamic deep brain stimulation in Parkinson’s disease might be accounted for by enhancement of prevailing high frequency oscillations.
Human subthalamic nucleus – Automatic auditory change detection as a basis for action selection
2017, Neuroscience
Citation Excerpt :
These data have been corroborated by diffusion tensor imaging studies in humans (e.g., Danielmeier et al., 2011; Forstmann et al., 2012; Rae et al., 2015; Xu et al., 2016). Moreover, using tracing studies, direct inputs from motor and sensory cortical areas, which would be critical in response selection, have been reported (e.g., Canteras et al., 1988; Kita et al., 2014). For example, in a recent tracing study in the rat by Kita et al. (2014) it was shown that cortico-subthalamic projections originating in motor and sensory areas sequentially innervate and form separate terminal fields in the STN and ZI.
The subthalamic nucleus (STN) shapes motor behavior and is important for the initiation and termination of movements. Here we ask whether the STN takes aggregated sensory information into account, in order to exert this function. To this end, local field potentials (LFP) were recorded in eight patients suffering from Parkinson’s disease and receiving deep-brain stimulation of the STN bilaterally. Bipolar recordings were obtained postoperatively from the externalized electrode leads. Patients were passively exposed to trains of auditory stimuli containing global deviants, local deviants or combined global/local deviants. The surface event-related potentials of the Parkinson’s patients as well as those of 19 age-matched healthy controls were characterized by a mismatch negativity (MMN) that was most pronounced for the global/local double deviants and less prominent for the other deviant conditions. The left and right STN LFPs similarly were modulated by stimulus deviance starting at about 100 ms post-stimulus onset. The MMN has been viewed as an index of an automatic auditory change detection system, more recently phrased in terms of predictive coding theory, which prepares the organism for attention shifts and for action. The LFP-data from the STN clearly demonstrate that the STN receives information on stimulus deviance, possibly as a means to bias the system to interrupt ongoing and to allow alternative actions.
Reaching to proprioceptively defined targets in Parkinson's disease: Effects of deep brain stimulation therapy
2013, Neuroscience
Citation Excerpt :
Our data indicate that there is a beneficial effect of STN DBS on the accuracy of multi-joint proprioception. Since the STN receives direct afferents from primary and secondary somatosensory cortices (Canteras et al., 1988; Juri et al., 2010) as well as from sensory processing areas of the thalamus (Lanciego et al., 2004), STN DBS could stimulate these somatosensory-related areas antidromically and interfere with their abnormal firing patterns, as well as those of cortical microcircuits of which they are a part (Li et al., 2007). Thus, STN DBS could override pathological synchronization within the cortico-basal ganglia sensorimotor loops improving limb localization accuracy.
Deep brain stimulation of the subthalamic nucleus (STN DBS) provides a unique window into human brain function since it can reversibly alter the functioning of specific brain circuits. Basal ganglia–cortical circuits are thought to be excessively noisy in patients with Parkinson’s disease (PD), based in part on the lack of specificity of proprioceptive signals in basal ganglia–thalamic–cortical circuits in monkey models of the disease. PD patients are known to have deficits in proprioception, but the effects are often subtle, with paradigms typically restricted to one or two joint movements in a plane. Moreover, the effects of STN DBS on proprioception are virtually unexplored. We tested the following hypotheses: first, that PD patients will show substantial deficits in unconstrained, multi-joint proprioception, and, second, that STN DBS will improve multi-joint proprioception. Twelve PD patients with bilaterally implanted electrodes in the subthalamic nucleus and 12 age-matched healthy subjects were asked to position the left hand at a location that was proprioceptively defined in 3D space with the right hand. In a second condition, subjects were provided visual feedback during the task so that they were not forced to rely on proprioception. Overall, with STN DBS switched off, PD patients showed significantly larger proprioceptive localization errors, and greater variability in endpoint localizations than the control subjects. Visual feedback partially normalized PD performance, and demonstrated that the errors in proprioceptive localization were not simply due to a difficulty in executing the movements or in remembering target locations. Switching STN DBS on significantly reduced localization errors from those of control subjects when patients moved without visual feedback relative to when they moved with visual feedback (when proprioception was not required). However, this reduction in localization errors without vision came at the cost of increased localization variability.
The 6-hydroxydopamine model: News from the past
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Citation Excerpt :
In fact, if the early subthalamic activation is linked to the initial decrease in the activity of GP, which maintains the STN under inhibitory (GABAergic) control [37–39], this mechanism cannot explain the further hyperactivity of the STN, which protracts for the whole observational period (4 weeks). In this case, it is likely that other areas projecting to the STN (such as the cerebral cortex [40,41] or the pedunculopontine nucleus [42]) intervene, influencing the activity of this nucleus once the nigrostriatal damage is established. Versatility is another important characteristic of the 6-OHDA model.
The investigation of pathogenic and pathophysiological mechanisms of Parkinson's disease relies on experimental models reproducing, in the animal, the pathological and behavioural features of the disease. Despite the availability of innovative models, 6-hydroxydopamine (6-OHDA) remains the most widely used tool to induce a nigrostriatal lesion in the animal (rat). This is due to (1) the relatively low complexity and cost of the procedure, (2) the fact that the 6-OHDA-induced lesion is highly reproducible, and (3) the versatility of the procedure, which can yield varying degrees of nigrostriatal lesions that develop with different temporal profiles, depending on the site chosen for the toxin injection.
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2005, Experimental Neurology
The subthalamic nucleus (STN) is a crucial node in the basal ganglia. Clinical success in targeting the STN for deep brain stimulation in Parkinson's disease patients has prompted increased interest in understanding STN biology. In this report, we discuss recent evidence for transcription factor mediated regulation of STN development. We also review STN developmental neurobiology and known patterns of gene expression in the developing and mature STN.

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Somatosensory inputs to the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxidase study in the rat

Abstract

Light-microscopic analysis of Golgi-impregnated rat subthalamic neurons

J. Comp. Neurol.

Topographical projections of the cerebral cortex to the subthalamic nucleus

J. Comp. Neurol.

Functional role of sensory inputs to the motor cortex

Prog. Neurobiol.

Output systems of the dorsal column nuclei in the cat

Brain Res. Rev.

Neurological Anatomy in Relation to Clinical Medicine

Ballism

Anatomy of the Basal Ganglia

The projections of the entopeduncular nucleus and globus pallidus in rat as demonstrated by autoradiography and horseradish peroxidase histochemistry

J. Comp. Neurol.

Evidence for a viscerotopic sensory representation in the cortex and thalamus in the rat

J. Comp. Neurol.

Functional organization of thalamic projections to the motor cortex. An anatomical and electrophysiological study in the rat

Neuroscience

Primate models of dyskinesia: the experimental approach to the study of basal ganglia-related involuntary movements disorders

Neuroscience

Primate globus pallidus and subthalamic nucleus functional organization

J. Neurophysiol.

Functional organization of the basal ganglia: contributions of single-cell recording studies

The motor cortex of the rat: cytoarchitecture and microstimulation mapping

J. Comp. Neurol.

Basal ganglia outputs and motor control

Peripheral input to the rat subthalamic nucleus, an electrophysiological study

Neurosci. Lett.

Intracellular labelling of rat subthalamic neurones with horseradish peroxidase: computer analysis of dendrites and characterization of axon a arborization

Neuroscience

Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey

Exp. Brain Res.

Anterograde transsynaptic transport of WGA-HRP in rat olfactory pathways

Brain Research

An excitatory pathway through dorsal columns to rubrospinal cells in the cat

J. Physiol. (Lond.)

Turning behavior after unilateral lesion of the subthalamic nucleus in the rat

Behav. Brain Res.

Pallidai inputs to subthalamus: intracellular analysis

Brain Research

Efferent projections of the subthalamic nucleus in the rat: light and electron microscopic analysis with the PHA-L method

J. Comp. Neurol.

The cortical projections of the mediodorsal nucleus and adjacent thalamic nuclie in the rat

J. Comp. Neurol.

Nucleus z in the rat: spinal afferents from collaterals of dorsal spinocerebellar tract neurons

J. Comp. Neurol.