Genetic dissection of an amygdala microcircuit that gates conditioned fear

被引：620

作者：

Haubensak, Wulf ^{[1
]}

Kunwar, Prabhat S. ^{[1
]}

Cai, Haijiang ^{[1
]}

Ciocchi, Stephane ^{[3
]}

Wall, Nicholas R. ^{[4
]}

Ponnusamy, Ravikumar ^{[5
,6
]}

Biag, Jonathan ^{[7
]}

Dong, Hong-Wei ^{[7
]}

Deisseroth, Karl ^{[8
]}

Callaway, Edward M. ^{[4
]}

Fanselow, Michael S. ^{[5
,6
]}

Luethi, Andreas ^{[3
]}

Anderson, David J. ^{[1
,2
]}

机构：

[1] CALTECH, Div Biol 216 76, Pasadena, CA 91125 USA

[2] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

[3] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland

[4] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA

[5] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Lab Neuroimaging, Los Angeles, CA 90095 USA

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

来源：

NATURE | 2010年 / 468卷 / 7321期

关键词：

CENTRAL EXTENDED AMYGDALA; RAT CENTRAL NUCLEUS; BACTERIAL ARTIFICIAL CHROMOSOMES; NEURONS IN-VITRO; PERIAQUEDUCTAL GRAY; NEURAL CIRCUITS; BASAL GANGLIA; RABIES VIRUS; EXPRESSION; VIVO;

D O I：

10.1038/nature09553

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-delta (PKC-delta). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-delta(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-delta(-) neurons in CEl. Electrical silencing of PKC-delta(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.

引用

页码：270 / U230

页数：9

共 54 条

[1] A FLEX switch targets channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping [J].

Atasoy, Deniz ;

Aponte, Yexica ;

Su, Helen Hong ;

Sternson, Scott M. .

JOURNAL OF NEUROSCIENCE, 2008, 28 (28) :7025-7030

[2] A molecular and genetic arsenal for systems neuroscience [J].

Callaway, EM .

TRENDS IN NEUROSCIENCES, 2005, 28 (04) :196-201

[3] Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2 [J].

Cardin, Jessica A. ;

Carlen, Marie ;

Meletis, Konstantinos ;

Knoblich, Ulf ;

Zhang, Feng ;

Deisseroth, Karl ;

Tsai, Li-Huei ;

Moore, Christopher I. .

NATURE PROTOCOLS, 2010, 5 (02) :247-254

[4] NEURONAL ARCHITECTURE IN THE RAT CENTRAL NUCLEUS OF THE AMYGDALA - A CYTOLOGICAL, HODOLOGICAL, AND IMMUNOCYTOCHEMICAL STUDY [J].

CASSELL, MD ;

GRAY, TS ;

KISS, JZ .

JOURNAL OF COMPARATIVE NEUROLOGY, 1986, 246 (04) :478-499

[5] The intrinsic organization of the central extended amygdala [J].

Cassell, MD ;

Freedman, LJ ;

Shi, CJ .

ADVANCING FROM THE VENTRAL STRIATUM TO THE EXTENDED AMYGDALA: IMPLICATIONS FOR NEUROPSYCHIATRY AND DRUG ABUSE: IN HONOR OF LENNART HEIMER, 1999, 877 :217-241

[6] Characterization of neurons in the rat central nucleus of the amygdala: Cellular physiology, morphology, and opioid sensitivity [J].