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Showing posts from June, 2016

Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior

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Nice paper in Cell Reports:

Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females.

Firing patterns of serotonin neurons underlying cognitive flexibility

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Nice paper in bioarchivx

Nature Neuro: Using opto and chemogenetics to enhance tau propagation and tau pathology in vivo

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Chemogenetics to interrogate Interactions between respiratory oscillators

Nice paper combining allostatin Gi linked receptors and DREADDS in elife

DREADDs do not apparently desensitize in vivo

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As I recently suggested in an article in Neuron, because of receptor reserve when DREADDs are expressed desensitization is unlikely to occur to any significant extent.  We now have some nice validation of this basic principle of GPCR molecular pharmacology in a nice paper just published in Nature Communications.


Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action

Flp/Cre-dependent DREADD

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DREADDs defining ETOH actions on striatal D1 and D2 pathways

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Distinct Synaptic Strengthening of the Striatal Direct and Indirect Pathways Drives Alcohol Consumption
In this study, we measured both glutamatergic and GABAergic activity in D1-MSNs and D2-MSNs and found that NMDA receptor (NMDAR) activity in D1-MSNs and GABAergic activity in D2-MSNs were selectively potentiated following cycles of alcohol consumption and withdrawal. Using a chemogenetic approach employing designer receptors exclusively activated by designer drugs (DREADDs), which allowed selective manipulation of D1- or D2-MSN activity (23), we discovered that both of these cell types were not only necessary, but also sufficient, to drive alcohol consumption. Furthermore, we observed that D2R-glycogen synthase kinase-3β (GSK3β) signaling regulated GABAergic activity and thus, alcohol consumption. The findings of this study provide detailed mechanistic information indicating how different forms of neuroplasticity in distinct neuronal populations of the striatal direct and indirect p…