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:
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- 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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