Molecularly stratified hypothalamic astrocytes are cellular foci for obesity.

Astrocytes safeguard the homeostasis of the central nervous system. Despite their prominent morphological plasticity under conditions that challenge the brain's adaptive capacity, the classification of astrocytes, and relating their molecular make-up to spatially devolved neuronal operations that specify behavior or metabolism, remained mostly futile. Although it seems unexpected in the era of single-cell biology, the lack of a major advance in stratifying astrocytes under physiological conditions rests on the incompatibility of 'neurocentric' algorithms that rely on stable developmental endpoints, lifelong transcriptional, neurotransmitter, and neuropeptide signatures for classification with the dynamic functional states, anatomic allocation, and allostatic plasticity of astrocytes.

Cellular and Behavioral Characterization of Mutant Mice: subtle Molecular Changes, Increased Exploratory Behavior and an Impact of Social Environment.

Mutations in the X-linked cell adhesion protein PCDH19 lead to seizures, cognitive impairment, and other behavioral comorbidities when present in a mosaic pattern. Neither the molecular mechanisms underpinning this disorder nor the function of PCDH19 itself are well understood. By combining RNA hybridization with immunohistochemistry and analyzing single-cell RNA sequencing datasets, we reveal expression in cortical interneurons and provide a first account of the subtypes of neurons expressing /, both in the mouse and the human cortex.

Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress.

Electrophysiological and neurochemical studies implicate cholinergic signaling in the basolateral amygdala (BLA) in behaviors related to stress. Both animal studies and human clinical trials suggest that drugs that alter nicotinic acetylcholine receptor (nAChR) activity can affect behaviors related to mood and anxiety. Clinical studies also suggest that abnormalities in cholinergic signaling are associated with major depressive disorder, whereas pre-clinical studies have implicated both β2 subunit-containing (β2*) and α7 nAChRs in the effects of nicotine in models of anxiety- and depression-like behaviors.

Expression of the 5-HT1A serotonin receptor in the hippocampus is required for social stress resilience and the antidepressant-like effects induced by the nicotinic partial agonist cytisine.

Nicotinic acetylcholine receptor (nAChR) blockers potentiate the effects of selective serotonin reuptake inhibitors (SSRIs) in some treatment-resistant patients; however, it is not known whether these effects are independent, or whether the two neurotransmitter systems act synergistically. We first determined that the SSRI fluoxetine and the nicotinic partial agonist cytisine have synergistic effects in a mouse model of antidepressant efficacy, whereas serotonin depletion blocked the effects of cytisine. Using a pharmacological approach, we found that the 5-HT1A agonist 8-OH-DPAT also potentiated the antidepressant-like effects of cytisine, suggesting that this subtype might mediate the interaction between the serotonergic and cholinergic systems.