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ref: Wichmann-1994.08 tags: STN normal physiology delong wichmann date: 02-27-2012 22:05 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-7983514[0] The Primate Subthalamic Nucleus. 1. Functional Properties in Intact Animals.

  • Lots of cells -- 301 cells in the STN, 1589 microstimulation sites, 72 cross-correlation pairs.
  • 55% modulated to passive contralateral movement, 86% of these to muscle palpitation, 25% to light touch.
  • Caudalventral STN devoid of calls responding to touch or movement.
  • Somatotopic organization: lateral arm, medial leg.
    • Representation of proximal muscles / portions much larger than distal portions, consistent with Carpenter 1950.
  • Mostly rate increases in response to step tracking tasks, usually uniphasic.
  • 40ua, 200-500 ms train duration, 400 Hz did not produce movement. Stimulation of the lateral borders often led to eye movements.
  • 11% of pairs were seen to be synchronized, separated by 100-200um.
    • Much smaller than in the cortex.
    • This strongly supports the concept of functional segregation in the basal ganglia-thalamocortical pathways.
  • Mean firing rate 23 Hz old studies, 19 Hz present study.
  • "Most hypotheses concerning the role of the basal ganglia in movement were derived from experience with diseases originating in the basal ganglia or from experiments involving the activation or inactivation of large parts of BG nuclei. These results are notoriously hard to interpret, because gross changes in motor circuit activity likely results in rather nonspecific activity changes in multiple parts of the neuraxis, unlike minute alterations in the firing patterns of individual neurons in the basal ganglia may have under physiological conditions".
  • Basal ganglia may have a role in the late phases of movement, perhaps even their termination.
  • "More is known about the role of the indirect pathway in the pathophysiology of movement disorders such as Parkinson's disease and ballism than in the control of normal movement." word, yes.

____References____

[0] Wichmann T, Bergman H, DeLong MR, The primate subthalamic nucleus. I. Functional properties in intact animals.J Neurophysiol 72:2, 494-506 (1994 Aug)

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ref: Wichmann-2011.12 tags: DBS STN basal ganglia bursts oscillation review wichmann beta date: 02-22-2012 17:05 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-21723919[0] Pathological basal ganglia activity in movement disorders.

  • The paradigm has shifted: initial idea was that firing rates changed,
  • later in detailed description of basal ganglia firing rate changes:
    • burst patterns and oscillations
  • 6-OHDA murines + MPTP monkey models so essential yada yada.
  • intraoperative microelectrode recordings yada yada.
  • Nice figure:
    • Black = inhibitory; gray = excitatory. From Galvan and Wichmann 2008.
    • note differences between D2 and D1.
  • Recall corticostriatal fibers are often (50%) collaterals from corticospinal axons.
  • Corticostriatal pathway separate from cortico-subthalamic pathway, so the two get different signals. (Parent and Parent 2006).
    • Few collaterals, and of those axons go to red nucleus and cerebral peduncle -- not pyramids.
  • Indirect (GPe, STN targets) and direct (GPi/SNr) striatal projections generally, but not completely, seem separate.
  • VA = ventroanterior; VL = ventrolateral thalamus.
  • Collaterals from GPi/SNr reach the intralaminar thalamic nuclei: the CM (centromedian) and the PF (parafascicular) nuclei.
  • One of the important additional function of the intralaminar thalamic nuclei is to provide saliency information to the striatum during procedural learning (Kimura et al 2004; Minamimoto et al 2009).
  • There is a considerable body of evidence that the absence of dopaminergic transmission may trigger changes in the density and morphology of dendritic spines on striatal projection neurons.
    • Thereby influencing corticostriatal transmission.
    • This is consistent with the progressive nature of the disease.
  • Serotonin and acetylcholine also involved in striatum, but their role in PD less well characterized.
  • Tremor and dystonia possibly due to afferents from the deep cerebellar nuclei and efferents to the cerebellar cortex.
  • Rate model failures:
    • thalamotomy procedures did not result in worsening of parkinsonism.
    • GPi lesions produced bradykinesia in normal monkeys (despite the GABA output!)
    • GPe lesions do not produce parkinsonism.
    • not all studies report changes in FR in GPi/GPe.
    • A significant factor interfering with the assessment of FR changes in PD patients is that its dependent on the state of arousal of the patients.
  • Burstiness: Increased burstiness (Fig. 2A) has emerged as one of the most reliable abnormalities of neuronal firing in the basal ganglia in parkinsonism, as shown in dopamine-depleted monkeys and in patients with PD
  • Oscillations: much in the beta band (10-35 Hz) throughout extrastriatal BG.
old redirect: see [1]
  • LFP power:
  • Brown is the purveyor of the high kinetic / low akinetic hypothesis (2003, 2005).
  • Oscillations do not occur in acute dopamine depletion.
  • GABA receptor blockade in GPe results in dyskinesias.
  • STN inactivation results in ballismus, as noted elsewhere.
  • GPi lesioning is clinically used to abolish dyskinesias in patients with treatment-resistant hyperkinetic movements.

____References____

[0] Wichmann T, Dostrovsky JO, Pathological basal ganglia activity in movement disorders.Neuroscience 198no Issue 232-44 (2011 Dec 15)
[1] Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA, The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.Brain 124:Pt 9, 1777-90 (2001 Sep)

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ref: Wichmann-1999.04 tags: parkinsons basal ganglia substantia nigra date: 0-0-2007 0:0 revision:0 [head]

PMID-10323285 Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substania nigra pars reticulata

  • putamen = motor portion of the striatum.
  • basal ganglia output is directed toward the ventral anterior, ventrolateral, and centromedial nuclei of the thalamus, which, in turn, project back to the cortex. Plus, the output of the basal ganglia project to the cortex.
  • MPTP induces excessive 3-8 Hz bursts in the GPi (e.g. correlated with tremor).