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ref: -0 tags: optogenetics micro LED flexible electrodes PET rogers date: 12-28-2017 03:24 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-23580530 Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

  • Supplementary materials
  • 21 authors, University Illinois at Urbana-Champaign, Tufts, China, Northwestern, Miami ..
  • GaN blue and green LEDs fabricated on a flexible substrate with stiff inserter.
    • Inserter is released in 15 min with a dissolving silk fibrin.
    • made of 250um thick SU-8 epoxy, reverse photocured on a glass slide.
  • GaN LEDS fabricated on a sapphire substrate & transfer printed via modified Karl-Suss mask aligner.
    • See supplemental materials for the intricate steps.
    • LEDs are 50um x 50um x 6.75um
  • Have integrated:
    • Temperature sensor (Pt serpentine resistor) / heater.
    • inorganic photodetector (IPD)
      • ultrathin silicon photodiode 1.25um thick, 200 x 200um^2, made on a SOI wafer
    • Pt extracellular recording electrode.
        • This insulated via 2um thick more SU-8.
  • Layers are precisely aligned and assembled via 500nm layer of epoxy.
    • Layers made of 6um or 2.5um thick mylar (polyethylene terephthalate (PET))
    • Layers joined with SU-8.
    • Wiring patterned via lift-off.
  • Powered via RF scavenging at 910 Mhz.
    • appeared to be simple, power in = light out; no data connection.
  • Tested vs control and fiber optic stimulation, staining for:
    • Tyrosine hydroxylase (makes l-DOPA)
    • c-fos, a neural activity marker
    • u-LEDs show significant activation.
  • Also tested for GFAP (astrocytes) and Iba1 (activated microglia); flexible & smaller devices had lower gliosis.
  • Next tested for behavior using a self-stimulation protocol; mice learned to self-stimulate to release DA.
  • Devices are somewhat reliable to 250 days!

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ref: Gradinaru-2009.04 tags: Deisseroth DBS STN optical stimulation 6-OHDA optogenetics date: 05-10-2016 23:48 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19299587[0] Optical Deconstruction of Parkinsonian Neural Circuitry.

  • Viviana Gradinaru, Murtaza Mogri, Kimberly R. Thompson, Jaimie M. Henderson, Karl Deisseroth
  • DA depletion of the SN leads to abnormal activity in the BG ; HFS (>90Hz) of the STN has been found to be therapeutic, but the mechanism is imperfectly understood.
    • lesions of the BG can also be therapeutic.
  • Used chanelrhodopsin (light activated cation channel (+)) which are expressed by cell type specific promoters. (transgenic animals). Also used halorhodopsins, which are light activated chloride pumps (inhibition).
    • optogenetics allows simultaneous optical stimulation and electrical recording without artifact.
  • Made PD rats by 6-hydroxydopamine unilaterally into the medial forebrain bundle of rats.
  • Then they injected eNpHr (inhibitory) opsin vector targeting excitatory neurons (under control of the CaMKIIa receptor) to the STN as identified stereotaxically & by firing pattern.
    • Electrical stimulation of this area alleviated rotational behavior (they were hemiparkinsonian rats), but not optical inhibition of STN.
  • Alternately, the glia in STN may be secreting molecules that modulate local circuit activity; it has been shown that glial-derived factor adenosine accumulates during DBS & seems to help with attenuation of tremor.
    • Tested this by activating glia with ChR2, which can pass small Ca+2 currents.
    • This worked: blue light halted firing in the STN; but, again, no behavioral trace of the silencing was found.
  • PD is characterized by pathological levels of beta oscillations in the BG, and synchronizing STN with the BG at gamma frequencies may ameliorate PD symptoms; while sync. at beta will worsen -- see [1][2]
  • Therefore, they tried excitatory optical stimulation of excitatory STN neurons at the high frequencies used in DBS (90-130Hz).
    • HFS to STN failed, again, to produce any therapeutic effect!
  • Next expressed channel rhodopsin in only projection neurons Thy1::ChR2 (not excitatory cells in STN), again did optotrode (optical stim, eletrical record) recordings.
    • HFS of afferent fibers to STN shut down most of the local circuitry there, with some residual low-amplitude high frequency burstiness.
    • Observed marked effects with this treatment! Afferent HFS alleviated Parkinsonian symptoms, profoundly, with immediate reversal once the laser was turned off.
    • LFS worsened PD symptoms, in accord with electrical stimulation.
    • The Thy1::ChR2 only affected excitatory projections; GABAergic projections from GPe were absent. Dopamine projections from SNr were not affected by the virus either. However, M1 layer V projection neurons were strongly labeled by the retrovirus.
      • M1 layer V neurons could be antidromically recruited by optical stimulation in the STN.
  • Selective M1 layer V HFS also alleviated PD symptoms ; LFS had no effect; M2 (Pmd/Pmv?) LFS causes motor behavior.
  • Remind us that DBS can treat tremor, rigidity, and bradykinesia, but is ineffective at treating speech impairment, depression, and dementia.
  • Suggest that axon tract modulation could be a common theme in DBS (all the different types..), as activity in white matter represents the activity of larger regions compactly.
  • The result that the excitatory fibers of projections, mainly from the motor cortex, matter most in producing therapeutic effects of DBS is counterintuitive but important.
    • What do these neurons do normally, anyway? give a 'copy' of an action plan to the STN? What is their role in M1 / the BG? They should test with normal mice.

____References____

[0] Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K, Optical Deconstruction of Parkinsonian Neural Circuitry.Science no Volume no Issue no Pages (2009 Mar 19)
[1] Eusebio A, Brown P, Synchronisation in the beta frequency-band - The bad boy of parkinsonism or an innocent bystander?Exp Neurol no Volume no Issue no Pages (2009 Feb 20)
[2] Wingeier B, Tcheng T, Koop MM, Hill BC, Heit G, Bronte-Stewart HM, Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.Exp Neurol 197:1, 244-51 (2006 Jan)

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ref: -0 tags: micro LEDS Buzaki silicon neural probes optogenetics date: 04-18-2016 18:00 gmt revision:0 [head]

PMID-26627311 Monolithically Integrated ╬╝LEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals.

  • 12 uLEDs and 32 rec sites integrated into one probe.
  • InGaN monolithically integrated LEDs.
    • Si has ~ 5x higher thermal conductivity than sapphire, allowing better heat dissipation.
    • Use quantum-well epitaxial layers, 460nm emission, 5nm Ni / 5nm Au current injection w/ 75% transmittance @ design wavelength.
      • Think the n/p GaN epitaxy is done by an outside company, NOVAGAN.
    • Efficiency near 80% -- small LEDs have fewer defects!
    • SiO2 + ALD Al2O3 passivation.
    • 70um wide, 30um thick shanks.

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ref: -0 tags: maleimide azobenzine glutamate photoswitch optogenetics date: 06-16-2014 21:19 gmt revision:0 [head]

PMID-16408092 Allosteric control of an ionotropic glutamate receptor with an optical switch

  • 2006
  • Use an azobenzene (benzine linked by two double-bonded nitrogens) as a photo-switchable allosteric activator that reversibly presents glutamate to an ion channel.
  • PIMD:17521567 Remote control of neuronal activity with a light-gated glutamate receptor.
    • The molecule, in use.
  • Likely the molecule is harder to produce than channelrhodopsin or halorhodopsin, hence less used. Still, it's quite a technology.

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ref: -0 tags: optogenetics glutamate azobenzine date: 05-07-2014 19:51 gmt revision:0 [head]

PMID-17521567 Remote control of neuronal activity with a light-gated glutamate receptor.

  • Neuron 2007.
  • azobenzines undergo a cis to trans confirmational change via illumination with one wavelength, and trans to cis via another. (neat!!)
  • This was used to create photo-controlled (on and off) glutamate channels.

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ref: -0 tags: Anna Roe optogenetics artificial dura monkeys intrinisic imaging date: 09-30-2013 19:08 gmt revision:3 [2] [1] [0] [head]

PMID-23761700 Optogenetics through windows on the brain in nonhuman primates

  • technique paper.
  • placed over the visual cortex.
  • Injected virus through the artificial dura -- micropipette, not CVD.
  • Strong expression:
  • See also: PMID-19409264 (Boyden, 2009)

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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.