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ref: -0 tags: Disseroth Kreitzer parkinsons optogenetics D1 D2 6OHDA date: 09-30-2013 18:15 gmt revision:0 [head]

PMID-20613723 Regulation of parkinsonian motor behaviors by optogenetic control of basal ganglia circuitry

  • Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC.
  • Generated mouse lines with channelrhodopsin2, with Cre recombinase under control of regulatory elements for the dopamine D1 (direct) or D2 (indirect) receptor.
  • optogenetic exitation of the indirect pathway elicited a parkinsonian state: increased freezing, bradykinesia and decreased locomotor initiations;
  • Activation of the direct pathway decreased freezing and increased locomotion.
  • Then: 6OHDA depletion of striatal dopamine neurons.
  • Optogenetic activation of direct pathway (D1 Cre/loxp) neurons restored behavior to pre-lesion levels.
    • Hence, this seems like a good target for therapy.

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ref: Shapovalova-2006.1 tags: dopamine learning neocortex rats russians D2 date: 03-12-2007 01:58 gmt revision:0 [head]

PMID-17216714 Motor and cognitive functions of the neostriatum during bilateral blocking of its dopamine receptors

  • systemic application of D1 selective blockers reduced learning in rats
    • probably this effect is not neostriatal:
  • local application of the same blocker on the cortex did not markedly affect learning, though it did effect initiation errors
  • D2 antagonist (raclopride) locally applied to the striatum blocked learning.

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ref: neuro notes-0 tags: Dopamine receptor D1 D2 date: 0-0-2007 0:0 revision:0 [head]

http://www.cnsforum.com/imagebank/section/receptor_systems_Dopaminergic/default.aspx

  • the D1 receptor is coupled to stimulatory G-proteins, which cause cell depolarization. (pathway: stimulatory g-protein -> actibation of adenylate cyclase converts ATP -> cAMP -> PKC -> phosphorylation of sodium (and calcium?) channel.
  • the D2 receptor (family?) is coupled to inhibitory G-proteins, which decrease the activity of adenylate cyclase. this is a pretty vague picture.