ChAT-ChR2-EYFP Mice Have Enhanced Motor Endurance But Show Deficits in Attention and Several Additional Cognitive Domains

被引：94
作者：
Kolisnyk, Benjamin [1 ,2 ]
Guzman, Monica S. [1 ,3 ]
Raulic, Sanda [1 ]
Fan, Jue [1 ]
Magalhaes, Ana C. [1 ,4 ]
Feng, Guoping [6 ]
Gros, Robert [1 ,3 ,5 ]
Prado, Vania F. [1 ,2 ,3 ,4 ]
Prado, Marco A. M. [1 ,2 ,3 ,4 ]
机构：
[1] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada
[2] Univ Western Ontario, Grad Program Neurosci, London, ON N6A 5K8, Canada
[3] Univ Western Ontario, Dept Physiol & Pharmacol, Schulich Sch Med & Dent, London, ON N6A 5K8, Canada
[4] Univ Western Ontario, Dept Anat & Cell Biol, Schulich Sch Med & Dent, London, ON N6A 5K8, Canada
[5] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, London, ON N6A 5K8, Canada
[6] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA
来源：
JOURNAL OF NEUROSCIENCE | 2013年 / 33卷 / 25期
基金：
加拿大自然科学与工程研究理事会; 加拿大健康研究院; 加拿大创新基金会;
关键词：
VESICULAR ACETYLCHOLINE TRANSPORTER; REACTION-TIME-TASK; MORRIS WATER MAZE; HIPPOCAMPAL SYNAPTIC PLASTICITY; CHOLINERGIC GENE LOCUS; NICOTINIC RECEPTORS; PREFRONTAL CORTEX; SPATIAL MEMORY; KNOCKOUT MICE; ANIMAL-MODEL;
D O I：
10.1523/JNEUROSCI.0395-13.2013
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Acetylcholine (ACh) is an important neuromodulator in the nervous system implicated inmanyforms of cognitive and motor processing. Recent studies have used bacterial artificial chromosome (BAC) transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2-EYFP) to dissect cholinergic circuit connectivity and function using optogenetic approaches. We report that a mouse line used for this purpose also carries several copies of the vesicular acetylcholine transporter gene (VAChT), which leads to overexpression of functional VAChT and consequently increased cholinergic tone. We demonstrate that these mice have marked improvement in motor endurance. However, they also present severe cognitive deficits, including attention deficits and dysfunction in working memory and spatial memory. These results suggest that increased VAChT expression may disrupt critical steps in information processing. Our studies demonstrate that ChAT-ChR2-EYFP mice show altered cholinergic tone that fundamentally differentiates them from wild-type mice.
引用
收藏
页码：10427 / 10438
页数：12
相关论文
共 59 条
  • [1] Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex
    Andreasen, Jesper T.
    Redrobe, John R.
    [J]. BEHAVIOURAL PHARMACOLOGY, 2009, 20 (03): : 286 - 295
  • [2] BEJANIN S, 1994, J BIOL CHEM, V269, P21944
  • [3] Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain α4 and β2 subunits
    Bell, Karen A.
    Shim, Hoon
    Chen, Ching-Kang
    McQuiston, A. Rory
    [J]. NEUROPHARMACOLOGY, 2011, 61 (08) : 1379 - 1388
  • [4] Cholinergic Deafferentation of the Neocortex Using 192 IgG-Saporin Impairs Feature Binding In Rats
    Botly, Leigh C. P.
    De Rosa, Eve
    [J]. JOURNAL OF NEUROSCIENCE, 2009, 29 (13) : 4120 - 4130
  • [5] Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing
    Cachope, Roger
    Mateo, Yolanda
    Mathur, Brian N.
    Irving, James
    Wang, Hui-Ling
    Morales, Marisela
    Lovinger, David M.
    Cheer, Joseph F.
    [J]. CELL REPORTS, 2012, 2 (01): : 33 - 41
  • [6] SPECIFIC VESICULAR ACETYLCHOLINE TRANSPORTER PROMOTERS LIE WITHIN THE FIRST INTRON OF THE RAT CHOLINE-ACETYLTRANSFERASE GENE
    CERVINI, R
    HOUHOU, L
    PRADAT, PF
    BEJANIN, S
    MALLET, J
    BERRARD, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (42) : 24654 - 24657
  • [7] Nicotine addiction and nicotinic receptors: lessons from genetically modified mice
    Changeux, Jean-Pierre
    [J]. NATURE REVIEWS NEUROSCIENCE, 2010, 11 (06) : 389 - 401
  • [8] Cholinergic modulation of a specific memory function of prefrontal cortex
    Croxson, Paula L.
    Kyriazis, Diana A.
    Baxter, Mark G.
    [J]. NATURE NEUROSCIENCE, 2011, 14 (12) : 1510 - 1512
  • [9] Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex
    Dalley, JW
    Theobald, DE
    Bouger, P
    Chudasama, Y
    Cardinal, RN
    Robbins, TW
    [J]. CEREBRAL CORTEX, 2004, 14 (08) : 922 - 932
  • [10] Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice
    de Castro, B. M.
    Pereira, G. S.
    Magalhaes, V.
    Rossato, J. I.
    De Jaeger, X.
    Martins-Silva, C.
    Leles, B.
    Lima, P.
    Gomez, M. V.
    Gainetdinov, R. R.
    Caron, M. G.
    Izquierdo, I.
    Cammarota, M.
    Prado, V. F.
    Prado, M. A. M.
    [J]. GENES BRAIN AND BEHAVIOR, 2009, 8 (01) : 23 - 35
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