Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation

Harris, Julie A.; Hirokawa, Karla E.; Sorensen, Staci A.; Gu, Hongcang; Mills, Maya; Ng, Lydia; Bohn, Phillip; Mortrud, Marty; Ouellette, Benjamin; Kidney, Jolene; Smith, Kimberly A.; Dang, Chinh; Sunkin, Susan M.; Bernard, Amy; Oh, Seung Wook; Madisen, Linda; Zeng, Hongkui

doi:10.3389/fncir.2014.00076

Cited by 418 publications

(435 citation statements)

References 43 publications

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“…Although this strategy effectively mimics the exact expression of a gene, endogenous expression of the target locus could be disrupted. That said, defects in endogenous parvalbumin expression that could account for our results have not been reported (48). Second, the PV, Arch, and ChR2 mouse lines, although all maintained on a C57BL6/J background, have been bred separately and thus could have undetected spontaneous mutations that have become fixed (genetic drift) that could result in physiological and behavioral differences.…”

Section: Discussionmentioning

confidence: 91%

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Weible

Piscopo

Rothbart

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce selfreported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior cingulate cortex (ACC), by using optogenetics to induce oscillations in activity, can produce behavioral changes. Mice were randomly assigned to groups and were given twenty 30-min sessions of light pulses delivered at 1, 8, or 40 Hz over 4 wk or were assigned to a no-laser control condition. Before and after the month all mice were administered a battery of behavioral tests. In the light/dark box, mice receiving cortical stimulation had more light-side entries, spent more time in the light, and made more vertical rears than mice receiving rhythmic cortical suppression or no manipulation. These effects on light/dark box exploratory behaviors are associated with reduced anxiety and were most pronounced following stimulation at 1 and 8 Hz. No effects were seen related to basic motor behavior or exploration during tests of novel object and location recognition. These data support a relationship between lower-frequency oscillations in the mouse ACC and the expression of anxiety-related behaviors, potentially analogous to effects seen with human practitioners of some forms of meditation.ne month of integrated mind body meditation (1), a form of mindfulness meditation, has been shown to reduce selfreported anxiety as measured by the Profile of Mood States, reduce the stress hormone cortisol, increase ventral anterior cingulate cortex (ACC) activity, and change the white matter pathways surrounding the ACC as measured by increased fractional anisotropy in diffusion tensor imaging studies (1-4). How might a purely mental exercise such as paying attention to the present moment work to produce these changes in behavior and brain connectivity (5)?Some of these changes, including those to white matter, were hypothesized to be related to the finding that meditation can increase frontal theta activity even when the person is at rest (6). The theta activity may increase the number of active oligodendrocytes leading to increased myelination, thereby improving connectivity between the ACC and other limbic areas. Moreover, theta activity in humans has been uniquely correlated with glucose metabolism in the ACC (7). Because the ventral ACC connects to the amygdala and is thought to regulate its activity (8), these changes in the brain could result in the reduced anxiety found following meditation training.To test this idea, we developed a mouse model in which various frequencies of oscillatory activity were induced in the ACC using optogenetics. Because mindfulness meditation has often been associated with reductions in anxiety and negative affect (9), we examined exploratory behavior in the light/dark box. In this ethological model of anxiet...

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Section: Discussionmentioning

confidence: 91%

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Weible

Piscopo

Rothbart

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…ChAT-IRES-Cre animals have been shown to effectively limit expression of Cre-dependent (DIO) constructs within cholinergic cell populations, particularly in the MHb (Fig. 2a) (Harris et al 2014). First, we examined whether engagement of Gq-coupled signaling increases firing of MHb ChAT expressing neurons.…”

Section: Chemogenetic Activation Of the Cholinergic Mhb Population Rementioning

confidence: 99%

Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior

et al. 2018

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Propensity to relapse, even following long periods of abstinence, is a key feature in substance use disorders. Relapse and relapse-like behaviors are known to be induced, in part, by re-exposure to drug-associated cues. Yet, while many critical nodes in the neural circuitry contributing to relapse have been identified and studied, a full description of the networks driving reinstatement of drug-seeking behaviors is lacking. One area that may provide further insight to the mechanisms of relapse is the habenula complex, an epithalamic region composed of lateral and medial (MHb) substructures, each with unique cell and target populations. Although well conserved across vertebrate species, the functions of the MHb are not well understood. Recent research has demonstrated that the MHb regulates nicotine aversion and withdrawal. However, it remains undetermined whether MHb function is limited to nicotine and aversive stimuli or if MHb circuit regulates responses to other drugs of abuse. Advances in circuit-level manipulations now allow for cell-type and temporally specific manipulations during behavior, specifically in spatially restrictive brain regions, such as the MHb. In this study, we focus on the response of the MHb to reinstatement of cocaine-associated behavior, demonstrating that cocaine-primed reinstatement of conditioned place preference engages habenula circuitry. Using chemogenetics, we demonstrate that MHb activity is sufficient to induce reinstatement behavior. Together, these data identify the MHb as a key hub in the circuitry underlying reinstatement and may serve as a target for regulating relapse-like behaviors.

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“…These important studies have highlighted several regions and cell types regulated by oxytocin, including somatostatin-positive interneurons of prefrontal cortex involved in sexual behavior (Nakajima et al, 2014) and serotonergic neurons of the raphe nuclei that control anxiety (Yoshida et al, 2009) and project to nucleus accumbens for social reward (Dölen et al, 2013). One caveat of these approaches is that transgene expression could interfere with the endogenous expression profile (Harris et al, 2014), especially given the large number of regulatory elements controlling transcription and tissue-specific localization of the oxytocin receptor (Gimpl and Fahrenholz, 2001).…”

Section: Introductionmentioning

confidence: 99%

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

et al. 2016

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Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent-infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition.

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Anatomical characterization of Cre driver mice for neural circuit mapping and manipulation

Cited by 418 publications

References 43 publications

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training

Medial habenula cholinergic signaling regulates cocaine‐associated relapse‐like behavior

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

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