PMID-2479133 The functional anatomy of basal ganglia disorders.
- Matrix neurons mainly containing substance P mainly project upon the GPi or SNr
- while those containing enkephalins project on the GPe.
- Striosome neurons projecting to the SNc contain mainly substance P.
- Classical hypothesis:
- Hyperkinetic disorders, which are characterized by an excess of abnormal movements, are postulated to result from the selective impairment of striatal neurons projecting to the lateral globus pallidus.
- These are suppressed by D2 receptor antagonists & exacerbated by dopamine agonists.
- Chorea is a primary example.
- Despite Huntingtons, traumatic, ischemic, or ablative lesions of the striatum in man or animals rarely produces chorea or atheosis (writhing movements).
- In HD, cholinergic agonists will alleviate choreoatheosis, while anti-cholinergic drugs exacerbate it.
- Hypokinetic disorders, such as Parkinson's disease, are hypothesized to result from a complex series of changes in the activity of striatal projection neuron subpopulations resulting in an increase in basal ganglia output.
- opposite of HD, exacerbated by D2 antagonists and ameliorated by DA agonists, as well as anti-cholinergics.
- Dystonia = the spontaneous assumption of unusual fixed postures lasting from seconds to minutes.
- Standard model suggests that striatal lesions should result in spontaneous movements, while this is not the case in man or other mammals. (less inhibition on GPi / SNr -> greater susceptibility of the thalamus to competing programs (?))
- hyperkinetic movements can be produced by infusing bicululline, a GABA receptor antagonist, into GPe -- silencing it.
- In early HD, when chorea is most prominent, there is a selective loss of striatal neurons projecting to the LGP (enkephalin staining).
- Substance P containing neurons are lost later in the disease.
- Administration of D2 antagonists increases the synthesis of enkephalins and pre-proenkephalin mRNA in the striatum.
- This presumably represents increases in neuronal activity.
- Inhibition of GPe neurons decreases hyperkinetic movements? But STN is excitatory? This does not add up.
- Hemiballismus may be caused by disinhibition of SNr (?) and the VA/VL/MD/CM-Pf thalamocortical projections.
Saccades:
- In both PD and HD, there are both increases in the latency of initiation of saccades, slowing of saccadic velocity, and interruption of saccades.
- In HD, there is an early loss of substance-P containing striatal terminals in the SNr, possibly resulting in over-inhibition of tectal neurons.
- HD patients cannot supress saccades to flashed stimulus.
- No abnormalities in saccadic control in tourette's syndrome.
- Hikosaka: suggest that caudate neurons involved in the initiation of saccades are part of a mechanism in which sensory data are evaluated in the context of learned behaviors and anticipated actions, and then used to initiate behavior.
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