12 Basal Ganglia Function Direct Pathway: interrupt tonic inhibition - Active before and during movementsInputs: majority of cortexmultiple parallel pathwaysOutput: thalamus, superior colliculus, cortex…“Upper Motoneurons”- High levels of efferent tonic inhibition- GABAergic outputDirect Pathway: interrupt tonic inhibitionIndirect Pathway: internal loop increases inhibition
13 Basal Ganglia Continued Cerebral CortexCorpus Striatum(caudate & putamen)Medium Spiny NeuronsGlobus Pallidus &Substantia NigraUpper MNsMedium Spiny Neuronsmajority of cells in striatum75,000,000 (!)labeled lineoccur in patches: striosomesnormally not tonicGlobus Pallidus1/100 number of m. spiny neurons750,000INTEGRATORhigh level tonic outputGABAergicPrimary pathway back to motorcortex is via internal G. P.
14 Direct Pathway (tonic only) Normal activity of the direct pathway = hypokinesia
15 Direct Pathway (phasic activation) Reduced activity of the direct pathway (GP) = hyperkinesia
16 Enhanced activity in the indirect pathway = hypokinesia
17 Parkinson’s Disease damage to Nigrostriatal cells medium spiny neuronsdamage to Nigrostriatal cells- increased thalamic inhibition- seldom can coordinate movementsbursts of activity
18 Parkinson’s Disease treatments Must attenuate activity in the Globus Pallidus- l-Dopa (there are several pharmacological treatments)- thalamotomy- pallidotomy
19 Huntington’s Disease sequence is known, protein function is not - yet medium spiny neuronssequence is known, proteinfunction is not - yetgenetic test is available- excessive excitabilityinvoluntary movementseventual loss of mental cohesion
20 Huntington’s Disease treatments Must augment activity in the Globus Pallidus- ACh (acetylcholine)- Striatal tissue implantsgenetic treatments (?)
26 Cerebellar Cell Types Purkinje Cells: (inhibitory) If there were a brain of the cerebellum, it would be the Purkinje cellsMossy Fibers: (excitatory)From: - pontine nuclei (via middle peduncle)- other pons / brainstem lociTo: - deep cerebellar nuclei- granule cellsGranule Cells: (most abundant in brain)From & To: cerebellar cortex… ~unipolarGive rise to: Parallel Fibers: (excitatory)Climbing Fibers: (excitatory)From: - inferior oliveTo: - Purkinje shaftLocal Interneurons:Basket CellsStellate CellsGolgi Cells(inhibitory)“control the flow of information through the cerebellar cortex”
28 Clinical Implications Normal Function (to reiterate):Smooth motor functions (reduce error)Coordinate target acquisitionLesion or Degeneration:Loss of smooth movementsRarely stop on target
29 CONCLUDING ADMONITION The ability to successfully complete an organized sequence of movements requires the appropriate coordination of MANY elements.Spatial organization(rubrospinal pathways, spinal signals, cerebellar integration)Temporal organization(cortical planning)Accuracy and uniformity(error measures, sensory integration)Sequencing(spinal circuitry)
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