GAD67-GFP knock-in mice have normal sleep–wake patterns and sleep homeostasis

Chen, Lichao; Mckenna, James T; Leonard, Michael Z.; Yanagawa, Yuchio; McCarley, Robert W.; Brown, Ritchie E.

doi:10.1097/wnr.0b013e32833655c4

Cited by 15 publications

(13 citation statements)

References 24 publications

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“…One potential disadvantage of knock-in animals is that the targeted gene is knocked-out, resulting in changes in the behavior being studied. However, the heterozygous GAD67-GFP knock-in animals used here have sleep patterns and EEG rhythms that are not noticeably different from those in wildtype animals (Chen et al, 2010). When considered together with previous studies (Tamamaki et al, 2003; Brown et al, 2008b; McKenna et al, 2010; McNally et al, 2011), our results suggest that GAD67-GFP knock-in mice can be used to study GABAergic neurons involved in sleep-wake control throughout the brain.…”

Section: Discussionmentioning

confidence: 92%

“…Male, heterozygous GAD67-GFP mice (RIKEN Bioresource Center, http://www.brc.riken.jp/lab/animal/en, strain RBRC03674) on a Swiss-Webster background were crossed with female wildtype Swiss-Webster mice to generate the animals used in this study. Although heterozygous animals lack one copy of the GAD67 gene, the sleep-wake behavior and cortical activation of these animals is indistinguishable from that of wildtype animals (Chen et al, 2010). Both male and female animals were used for neuroanatomical and electrophysiological investigations.…”

Section: Methodsmentioning

confidence: 99%

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Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

Mckenna

Yang

Franciosi

et al. 2013

J of Comparative Neurology

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136

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The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium-binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67-GFP knock-in mice) or PV+ neurons (PV-Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67-GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium-sized (15–20 μm) GFP+ neurons. Most medium and large-sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast-firing and spontaneously active in vitro. They exhibited prominent hyperpolarization-activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV-Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep.

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

Mckenna

Yang

Franciosi

et al. 2013

J of Comparative Neurology

Self Cite

136

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“…The generation of GAD67-GFP knock-in mice has been reported previously and used widely for detecting GABAergic neurons (Tamamaki et al, 2003; May et al, 2008; Young and Sun, 2009; Chen et al, 2010; Han et al, 2010; Bang and Commons, 2012). In our studies, the mice were housed in standard conditions (12 h light/dark cycles) with water and food available ad libitum .…”

Section: Methodsmentioning

confidence: 99%

Noise-induced hearing loss is correlated with alterations in the expression of GABAB receptors and PKC gamma in the murine cochlear nucleus complex

Kou¹,

Qu²,

Zhang³

et al. 2013

Front. Neuroanat.

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Noise overexposure may induce permanent noise-induced hearing loss (NIHL). The cochlear nucleus complex (CNC) is the entry point for sensory information in the central auditory system. Impairments in gamma-aminobutyric acid (GABA)—mediated synaptic transmission in the CNC have been implicated in the pathogenesis of auditory disorders. However, the role of protein kinase C (PKC) signaling pathway in GABAergic inhibition in the CNC in NIHL remains elusive. Thus, we investigated the alterations of glutamic acid decarboxylase 67 (GAD67, the chemical marker for GABA-containing neurons), PKC γ subunit (PKCγ) and GABAB receptor (GABABR) expression in the CNC using transgenic GAD67-green fluorescent protein (GFP) knock-in mice, BALB/c mice and C57 mice. Immunohistochemical results indicate that the GFP-labeled GABAergic neurons were distributed in the molecular layer (ML) and fusiform cell layer (FCL) of the dorsal cochlear nucleus (DCN). We found that 69.91% of the GFP-positive neurons in the DCN were immunopositive for both PKCγ and GABABR1. The GAD67-positive terminals made contacts with PKCγ/GABABR1 colocalized neurons. Then we measured the changes of auditory thresholds in mice after noise exposure for 2 weeks, and detected the GAD67, PKCγ, and GABABR expression at mRNA and protein levels in the CNC. With noise over-exposure, there was a reduction in GABABR accompanied by an increase in PKCγ expression, but no significant change in GAD67 expression. In summary, our results demonstrate that alterations in the expression of PKCγ and GABABRs may be involved in impairments in GABAergic inhibition within the CNC and the development of NIHL.

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“…Electrophysiological evidence has suggested a direct GABAergic projection from the DR to the prefrontal cortex (PFC) (Puig et al,2005), yet the contribution of GABA neurons to forebrain projections remains poorly understood. In an attempt to improve the visualization of GABA neurons in this study, we used a mouse line in which green fluorescent protein (GFP) is knocked into the GAD67 locus to specifically identify GABAergic neurons (Tamamaki et al,2003; Chen et al,2010). Using this mouse line, we examined the projections of GABA neurons in the DR to three forebrain regions: the PFC, nucleus accumbens (NAC), and lateral hypothalamus (LH).…”

mentioning

confidence: 99%

Forebrain GABAergic projections from the dorsal raphe nucleus identified by using GAD67–GFP knock‐in mice

Bang

Commons

2012

J of Comparative Neurology

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The dorsal raphe nucleus (DR) contains serotonergic (5-HT) neurons that project widely throughout the fore-brain. These forebrain regions also receive innervation from non–5-HT neurons in the DR. One of the main groups of non–5-HT neurons in the DR is γ-aminobutyric acid (GABA)ergic, but their projections are poorly understood due to the difficulty of labeling these neurons immunohistochemically. To identify GABAergic projection neurons within the DR in the current study, we used a knock-in mouse line in which expression of green fluorescent protein (GFP) is controlled by the glutamic acid decarboxylase (GAD)67 promotor. Projections of GAD67–GFP neurons to the prefrontal cortex (PFC), nucleus accumbens (NAC), and lateral hypothalamus (LH) were evaluated by using retrograde tract tracing. The location of GAD67–GFP neurons projecting to each of these areas was mapped by rostrocaudal and dorsoventral location within the DR. Overall, 16% of DR neurons projecting to either the PFC or NAC were identified as GAD67–GFP neurons. GAD67–GFP neurons projecting to the PFC were most commonly found ventrally, in the rostral two-thirds of the DR. NAC-projecting GAD67–GFP neurons had an overlapping distribution that extended dorsally. GAD67–GFP neurons made a larger contribution to the projection of the DR to the LH, accounting for 36% of retrogradely labeled neurons, and were widespread throughout the DR. The current data indicate that DR GABAergic neurons not only may have the capacity to influence local network activity, but also make a notable contribution to DR output to multiple forebrain targets.

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GAD67-GFP knock-in mice have normal sleep–wake patterns and sleep homeostasis

Cited by 15 publications

References 24 publications

Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

Noise-induced hearing loss is correlated with alterations in the expression of GABAB receptors and PKC gamma in the murine cochlear nucleus complex

Forebrain GABAergic projections from the dorsal raphe nucleus identified by using GAD67–GFP knock‐in mice

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