Gong, S, Doughty, M, Harbaugh, CR, Cummins, A, Hatten, ME, Heintz, N et al.. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J Neurosci 27: 9817-9823

Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2007; 27(37):9817-23. DOI: 10.1523/JNEUROSCI.2707-07.2007
Source: PubMed


Transgenic mouse lines are characterized with Cre recombinase driven by promoters of CNS-specific genes using bacterial artificialchromosome (BAC) constructs. BAC-Cre constructs for 10 genes (Chat, Th, Slc6a4, Slc6a2, Etv1, Ntsr1, Drd2, Drd1, Pcp2, and Cmtm5)produced 14 lines with Cre expression in specific neuronal and glial populations in the brain. These Cre driver lines add functional utility to the >500 BAC-EGFP (enhanced green fluorescent protein) transgenic mouse lines that are part of the Gene Expression Nervous System Atlas Project.

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    • "Results obtained with the GFP reporter mouse line show that the GM60 line targets more efficiently and selectively cholinergic neurons in corticopetal BF nuclei and striatum than in hippocampopetal medial septal nucleus and neocortex . The BAC used to generate the GM60 Cre line contains the first intron of the ChAT gene, thus also the vesicular ACh transporter gene (Bejanin et al. 1994; Roghani et al. 1994; Gong et al. 2007). Nonetheless, currents we measured in non-cre mice with same genetic background (α5−/− line) provided no evidence for enhanced nicotinic transmission in the GM60 line, in contrast with the hypercholinergic phenotype reported for another BAC-based ChAT-ChR2-YFP transgenic mouse line (Kolisnyk et al. 2013). "
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    ABSTRACT: Nicotinic excitation in neocortex is mediated by low-affinity α7 receptors and by high-affinity α4β2 receptors. There is evidence that α7 receptors are synaptic, but it is unclear whether high-affinity receptors are activated by volume transmission or synaptic transmission. To address this issue, we characterized responses of excitatory layer 6 (L6) neurons to optogenetic release of acetylcholine (ACh) in cortical slices. L6 responses consisted in a slowly decaying α4β2 current and were devoid of α7 component. Evidence that these responses were mediated by synapses was 4-fold. 1) Channelrhodopsin-positive cholinergic varicosities made close appositions onto responsive neurons. 2) Inhibition of ACh degradation failed to alter onset kinetics and amplitude of currents. 3) Quasi-saturation of α4β2 receptors occurred upon ACh release. 4) Response kinetics were unchanged in low release probability conditions. Train stimulations increased amplitude and decay time of responses and these effects appeared to involve recruitment of extrasynaptic receptors. Finally, we found that the α5 subunit, known to be associated with α4β2 in L6, regulates short-term plasticity at L6 synapses. Our results are consistent with previous anatomical observations of widespread cholinergic synapses and suggest that a significant proportion of these small synapses operate via high-affinity nicotinic receptors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Full-text · Article · May 2015 · Cerebral Cortex
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    • "To observe and manipulate their activities selectively, the best available approach is genetic targeting of protein-based sensors and effectors to specific cell types (Huang and Zeng, 2013). In mice, the Cre/lox recombination system is the most widely used approach to access specific cell types, utilizing gene promoters or loci with specific expression patterns (Gerfen et al., 2013; Gong et al., 2007; Madisen et al., 2010; Taniguchi et al., 2011). However, cell populations defined by Cre driver lines are often heterogeneous, encompassing multiple brain regions and/or multiple cell types (Harris et al., 2014). "
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    ABSTRACT: An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Mar 2015 · Neuron
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    • "The development and genotyping of the 5-HT Oxtr KO is similar to that of the forebrain Oxtr line (Lee et al. 2008): the conditional Oxtr KO line (B6.129(SJL)-Oxtr tm1.1Wsy /J) is crossed with a transgenic line expressing Cre recombinase under the control of serotonin transporter [Tg(Slc6a4-cre)ET33Gsat, originally on FVB/N background; generously provided by Charles Gerfen, NIMH; Gong et al. 2007]. In this line, the Slc6a4 promoter drives Cre recombinase expression in serotonergic neurons (Fig. 1, for dorsal and MR expression ). "
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    ABSTRACT: Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically-mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to eight of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. This article is protected by copyright. All rights reserved.
    Full-text · Article · Feb 2015 · Genes Brain and Behavior
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