Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement

被引：471

作者：

Witten, Ilana B. ^{[1
,2
,3
]}

Steinberg, Elizabeth E. ^{[4
,5
]}

Lee, Soo Yeun ^{[1
,6
]}

Davidson, Thomas J. ^{[1
]}

Zalocusky, Kelly A. ^{[1
,15
]}

Brodsky, Matthew ^{[1
,7
]}

Yizhar, Ofer ^{[1
,8
]}

Cho, Saemi L. ^{[4
]}

Gong, Shiaoching ^{[9
]}

Ramakrishnan, Charu ^{[1
]}

Stuber, Garret D. ^{[10
,11
]}

Tye, Kay M. ^{[1
,12
]}

Janak, Patricia H. ^{[4
,5
]}

Deisseroth, Karl ^{[1
,6
,13
,14
,15
]}

机构：

[1] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[2] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA

[3] Princeton Neurosci Inst, Princeton, NJ 08544 USA

[4] UCSF, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA

[5] UCSF, Grad Program Neurosci, San Francisco, CA 94158 USA

[6] Stanford Univ, CNC Program, Stanford, CA 94305 USA

[7] Univ Washington, Grad Program Neurobiol & Behav, Seattle, WA 98195 USA

[8] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel

[9] Rockefeller Univ, GENSAT Project, New York, NY 10065 USA

[10] Univ N Carolina, UNC Neurosci Ctr, Dept Psychiat, Chapel Hill, NC 27599 USA

[11] Univ N Carolina, UNC Neurosci Ctr, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA

[12] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA

[13] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA

[14] HHMI, Stanford, CA 94305 USA

[15] Stanford Univ, Grad Program Neurosci, Stanford, CA 94305 USA

来源：

NEURON | 2011年 / 72卷 / 05期

关键词：

VENTRAL TEGMENTAL AREA; INTRACRANIAL SELF-STIMULATION; POSITIVE REINFORCEMENT; NUCLEUS-ACCUMBENS; FOREBRAIN-BUNDLE; WORKING-MEMORY; NEURONS; REWARD; BRAIN; MODULATION;

D O I：

10.1016/j.neuron.2011.10.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Currently there is no general approach for achieving specific optogenetic control of genetically defined cell types in rats, which provide a powerful experimental system for numerous established neurophysiological and behavioral paradigms. To overcome this challenge we have generated genetically restricted recombinase-driver rat lines suitable for driving gene expression in specific cell types, expressing Cre recombinase under the control of large genomic regulatory regions (200-300 kb). Multiple tyrosine hydroxylase (Th)::Cre and choline acetyltransferase (Chat)::Cre lines were produced that exhibited specific opsin expression in targeted cell types. We additionally developed methods for utilizing optogenetic tools in freely moving rats and leveraged these technologies to clarify the causal relationship between dopamine (DA) neuron firing and positive reinforcement, observing that optical stimulation of DA neurons in the ventral tegmental area (VTA) of Th::Cre rats is sufficient to support vigorous intracranial self-stimulation (ICSS). These studies complement existing targeting approaches by extending the generalizability of optogenetics to traditionally non-genetically-tractable but vital animal models.

引用

页码：721 / 733

页数：13

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