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Basal Ganglia

Sophie Obayashi Neurotoxity 9 Englisch 51 Karten

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  1. 1subthalamic nucleus neuronsGlutamate
  2. 2cortex neuronspyramidal neurons
    glutamate
  3. 3striatum neuronsMSNs
    GABAergic
  4. 4GP neuronspallidal neurons
    GABAergic
  5. 5thalamic neuronsglutamate
  6. 6striatum subnucleicaudate nucleus
    putamen
    (or in rats, caudatoputamen)
  7. 7dorsal striatum components and projection targetcaudatoputamen --> GP
  8. 8ventral striatum components and projection targetnucleus accumbens (NAc) --> ventral pallidum
  9. 9striatum is unique becauseprojects AND receives input
  10. 10two main sources of brain blood supplycarotid artery
    vertebral artery
  11. 11circle of Willisregion of brain w/maximum vascularization, where many arteries meet
  12. 12vascular supply to striatumhas unique subset of blood supply arteries
  13. 13blood supply to putamen & GPmiddle cerebral artery (MCA)
    --> medial/lateral lenticulostriate arteries
    -->
  14. 14blood supply to internal capsule & (anteromedial section of) caudate nucleusanterior cerebral artery (ACA)
    --> recurrent artery of Heubner
    -->
  15. 15characteristics of medium spiny neurons (MSNs)-90% of striatum
    - spiny
    - GABAergic projections (inhibitory)
    - main target of extrinsic inputs to striatum
  16. 16striatal neurons1. MSNs
    2. interneurons
  17. 17characteristics of interneurons- GABAergic & Cholinergic
    - aspiny
  18. 18inputs to MSNs, type of NT input, location of synapse1. cortex, glutamatergic, head
    2. thalamus, glutamatergic, shaft
    3. gabaergic neurons, gabaergic, axon hillock and dendrites
    4. substantia nigra, dopaminergic, neck
  19. 19why is dopamine a neuromodulator? (2)1. excitatory/inhibitory effect depends on receptor it synapses on
    2. modulates cortical drive
    (regulates amount glutamate influences MSN to send out inhibitory signals)
  20. 20D1 receptor effectexcitatory
  21. 21D2 receptor effectinhibitory
  22. 22saccades definition and circuitryrapid eye movements, basal ganglia projection into frontel eye fold neurons (FEFs) of motor cortex
  23. 23output nuclei of basal gangliaglobus pallidus, net effect of basal ganglia is determined by amount that the globus pallidus is inhibited. goal = regulation of amount that gp sends out
    more inihibition of gp, more movement initiation
  24. 24divider of caudate nucleus and putameninternal capsule, white matter tract
  25. 25dorsal vs. ventral striatum subnuclei and projection targetsdorsal: caudatoputamen --> GP
    ventral: NAc --> ventral pallidum
  26. 26basal ganglia subnuclei (6)STN, CN, PUT, GP, SN, NAc
  27. 27transient vs. tonictransient: burst signals
    tonic: slow, continuous signals
  28. 28thalamocortical disinhibitory circuit1. cortex: excitatory, glutamatergic, pyramidal neurons -->
    2. striatum: transient inhibitory, GABAergic, MSN & interneurons -->
    3. globus pallidus: tonic inhibitory, GABAergic, pallidal neurons -->
    4. VA/VL thalamus: transient excitatory, glutamatergic neurons -->
    5. motor cortex: excitatory glutamatergic neurons -->
    6. excitatory lower motor neurons (muscles)
  29. 29role of spines on MSNsnumber and size of spines allow MSN to modulate amt input from dA and cortical neurons
  30. 30James Parkinson's name for PDparalysis agitans
  31. 31age of onsetmean - 55
    increased for post-menopausal
  32. 32genetic vs other PD onsetearlier or around 50 = mainly genetic
    after 50 = other
  33. 33neurochemical feats of PD1. decreased dAreceptors in SN & NAc
    2. decreased tyrosine hydroxylase (TH): iron dependent enzyme for dA synthesis
    3. decreased neuromelanin (dark stain) indicates loss of neurons
  34. 34neuropathological feats of PD1. nigrostriatal pathway neurons decreased, esp. projections from SNc to PUT
    2. decrease dA neurons in SN
    3. accumulation of alpha-synuclein lewy bodies & whether tagged for ubiquitination
  35. 35SN nuclei that degenerates in PDSN pars compacta
  36. 36location of "getting ready cells"basal ganglia
  37. 37basal ganglia outputs for movement & sensorymovement: see direct/indirect pathways
    sensory: caudatoputamen (-) --> substantia nigra (dA -) --> superior colliculi (multisensory integration center)
  38. 38PD etiology5-10% genetic mutations
    environmental toxins
    endogeous toxins (malnutrition, fructose, etc.)
  39. 39familial PD loci - gene - inheritance - phenotype1. PARK 1& 4 - alpha synuclein - autosomal dominant (AD) - early onset, lewy bodies
    2. PARK 2 - parkin - autosomal recessive (AR) - early onset, slow progression
    3. PARK 6 - PINK-1 - AR - early onset, slow progression
    4. PARK 7 - DJ-1 - AR - early onset, slow progression
    5. PARK 8 - LRRK2 - AD - classic PD
  40. 40normal alpha-synuclein functions (5)1. regulates synaptic vesicle size
    2. & recycling
    3. neg regulator of dA synthesis + release (prevents over-release)
    4. chaperone
    5. song acquisition (learning & memory?) telencephalic area
  41. 41main component of lewy bodies?alpha-synuclein (60%)
  42. 42alpha-synuclein expression & synthesis?enriched in presynaptic terminal
    naturally unfolded monomer
  43. 43a-synuclein role in familial neurodegeneration1. overexpression of WT or functional mutation --> fibrillogenesis (protofibrils - oligomers, fibrils - amyloid) --> lewy bodies /E3 mutation/oxidative stress?
  44. 44effect of lewy bodiesimpairs axonal transport
  45. 45E3 mutation effectimpairs UPS
  46. 46a-synuclein role in sporadic neurodegenerationoxidants --> production of ROS, quinones --> oxidative stress
    *low levels of glutathione (GSH) b/c downregulation of glutathione reductase
    *high levels iron and calcium (react with superoxide & hydrogen peroxide to form hydroxyl & autooxidation of dA)
    *products of monoamine oxidase B (MAO-B) mediated metabolism of dA (in astrocytes) include H202, which in presence of metals will make OH*
  47. 47(normal) neuroprotective functions of parkin*counteracts a-synuclein activity?
    protects against:
    1. mitochondria-mediated apoptosis
    2. dA & KA-induced toxicity
    3. cultured neurons against cell death induced over-expression of cell death mediator proteins (p38)
    4. cultured dA neurons against toxicity via a-synuclein overexpression & proteasomal inhibition
    5. in vivo: SN dA neurons against degen by viral mutant a-synuclein
  48. 48parkin's role in PDE3 ubiquitin protein ligase in protein degradation pathway
    - mutations cause juvenile/early onset PD!
  49. 49lewy bodies in parkin induced PD?no
  50. 50other mutated genes in PD?UCHL1 gene: thiol protease that recognizes & recycles ubiquitin --> familial PD
    *mutations allow for increase of a-synuclein
  51. 51—

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9 Neurotoxity Karteikarten am Basal Ganglia, erstellt von Sophie Obayashi am 28/11/2015.
Erstellt von
Sophie Obayashi
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