Sex differences in animal models of decision making

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137573/1/jnr23810.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137573/2/jnr23810_am.pd

Sex differences, gender and addiction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134421/1/jnr23963_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134421/2/jnr23963.pd

<i>In-vivo</i> fiber-optic optogenetic stimulation using single (blue) vs two-photon (NIR) stimulation.

<p>(a) Set-up for <i>in-vivo</i> single and two-photon fiber-optic optogenetic stimulation and electrophysiological recording. Inset in right: Glass electrode and fiber based optrode. (b) <i>In-vivo</i> raw spiking of locally stimulated neurons (upper panel) corresponding to two-photon stimulation (shutter opening: lower panel) at 870 nm. (c) Peak-amplitude of recorded local electrical activity as a function of incident power density of <i>in-vivo</i> fiber-optic TPOS at two different wavelengths (also shown fitted lines). (d) Variation of peak amplitude of single photon (473 nm)-activated local electrical activity as a function of power density. (e) Peak-amplitude as a function of pulse width of <i>in-vivo</i> fiber-optic TPOS (870 nm) at two different power densities.</p

Depth-dependent <i>in-vivo</i> fiber-optic single and two-photon optogenetic stimulation.

<p>Sketch showing in-depth stimulation limit of fiber-optic (a) blue (single-photon) vs (b) NIR (two-photon) light. Different cortical layers are marked by blue lines. Raw electrical recording at 3 mm depth for (c) single photon (473 nm, 4 mW) and (d) two-photon (870 nm, 80 mW) stimulation. (e) Overlay of raw spikes (red profiles) with shutter (fiber-optic two-photon stimulation ON) opening (black profiles) at different depths for two different wavelengths. Also shown are representative single photon signals (blue profiles) at different depths, with shutter-ON marked by black profiles. (f) Comparison of latency of spikes at different depths stimulated by single photon and two-photon (870 nm) fiber-optic beams. *: p<0.05. (g) Histogram of latency of spikes at different two-photon wavelengths for three depths. *: p<0.05 vs. latency at 1 mm. (h) Variation of latency as a function of depth for different two-photon (870 nm) power densities.</p

Non-Scanning Fiber-Optic Near-Infrared Beam Led to Two-Photon Optogenetic Stimulation <i>In-Vivo</i>

<div><p>Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons <i>in-vivo</i> in transgenic mouse models. In order to optimize the deep-brain stimulation strategy, we characterized two-photon activation efficacy at different near-infrared laser parameters. The significantly-enhanced in-depth stimulation efficiency of FO-TPOS as compared to conventional single-photon beam was demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO-TPOS technology will lead to better understanding of the <i>in-vivo</i> neural circuitry because this technology permits more precise and less invasive anatomical delivery of stimulation.</p></div

Two-photon Optogenetic stimulation.

<p>Schematic comparison: (a) single-photon blue excitation, (b) single-photon red-shifted excitation and (c) two-photon optogenetic stimulation (TPOS). (d) Intensity profile emanating from the multimode fiber, scale bar: 100 µm, (e) Spectrum of ultrafast tunable near-infrared fiber-optic beam, (f) Two-photon fluorescence (green) from polystyrene particle excited by multimode profile. In-vitro two-photon activation of ChR2-expressing cells with ultrafast NIR laser beam: (g) Representative current responses to ultrafast NIR laser beam at different wavelengths (in nm), (h) Fiber-optic two-photon activation spectrum at 0.02 mW/µm² (100 ms pulses).</p

In-depth fiber-optic optogenetic stimulation using single (blue) vs two-photon (NIR).

<p>Monte Carlo simulation of light propagation in two-layered cortex for beam diameter of 60 µm, with laser power of 5 mW, (a) two-photon and (b) single-photon Gaussian beam. The color bar has unit of ln(W/cm²). Confocal immunofluorescence images of a deep brain region of Thy1-ChR2-YFP transgenic mice: (c) YFP, (d) tyrosine hydroxylase (TH), (e) composite image. Arrows point to examples of colocalized YFP-ChR2 in dopaminergic neurons. (f) Raw spiking activity at different depths due to <i>in-vivo</i> fiber-optic two-photon optogenetic stimulation (FO-TPOS). (g) Comparison of single and two-photon activated depth-dependent peak amplitude. *: p<0.05 vs. single photon. (h) Variation of peak amplitude of two-photon (850 nm)-activated local electrical activity as a function of depth at different power densities. (i) Comparison of peak-amplitude at two different wavelengths of <i>in-vivo</i> fiber-optic TPOS at different depths.</p