Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both cultured cells and animal models. However, delivering large dCas9 fusion proteins to target cells and tissues is an obstacle to the widespread adoption of these tools for in vivo studies.

Caveolin-1 regulates medium spiny neuron structural and functional plasticity.

Rationale: Caveolin-1 (CAV1) is a structural protein critical for spatial organization of neuronal signaling molecules. Whether CAV1 is required for long-lasting neuronal plasticity remains unknown.

Objective And Methods: We sought to examine the effects of CAV1 knockout (KO) on functional plasticity and hypothesized that CAV1 deficiency would impact drug-induced long-term plasticity in the nucleus accumbens (NAc).

Transcribing Memories in Genome Architecture.

Whether dynamic changes in genome architecture underlie transcriptional and functional plasticity in mature neurons has been technically challenging to address. A recent study (Yamada et al., Nature, 2019) exploited experimental advantages of the cerebellum to reveal cell type-specific changes in chromatin architecture that coordinate neural activity-induced changes in gene transcription and contribute to sensorimotor learning.

Palmitoylation of caveolin-1 is regulated by the same DHHC acyltransferases that modify steroid hormone receptors.

Palmitoylation is a reversible post-translational addition of a 16-carbon lipid chain involved in trafficking and compartmentalizing target proteins. It is important for many cellular functions, including signaling via membrane-localized estrogen receptors (ERs). Within the nervous system, palmitoylation of ERα is necessary for membrane surface localization and mediation of downstream signaling through the activation of metabotropic glutamate receptors (mGluRs).

Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females.

Contribution to Special Issue on Fast effects of steroids. Estrogen receptors α and β (ERα and ERβ) have a unique relationship with metabotropic glutamate receptors (mGluRs) in the female rodent brain such that estradiol is able to recruit intracellular G-protein signaling cascades to influence neuronal physiology, structure, and ultimately behavior. While this association between ERs and mGluRs exists in many cell types and brain regions, its effects are perhaps most striking in the nucleus accumbens (NAc).

Membrane estrogen receptor signaling impacts the reward circuitry of the female brain to influence motivated behaviors.

Within the adult female, estrogen signaling is well-described as an integral component of the physiologically significant hypothalamic-pituitary-gonadal axis. In rodents, the timing of ovulation is intrinsically entwined with the display of sexual receptivity. For decades, the importance of estradiol activating intracellular estrogen receptors within the hypothalamus and midbrain/spinal cord lordosis circuits has been appreciated.