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Starnes, W. D.

Publications and source records attributed to Starnes, W. D..

2 recordsLinked to original sources

Adolescent binge drinking leads to long lasting changes in cortical microcircuits

Adolescent drug consumption has increased risks to the individual compared to consumption in adulthood, due to the likelihood of long-term and permanent behavioral and neurological adaptations. However, little is known about how adolescent alcohol consumption influences the maturation and trajectory of cortical circuit development. Here, we explore the consequences of adolescent binge drinking on somatostatin (SST) neuronal function in superficial layers of the prelimbic (PL) cortex in male and female SST-Ai9 mice. We find that adolescent drinking-in-the-dark (DID) produces sex-dependent increases in intrinsic excitability of SST neurons, with no change in overall SST cell number, persisting well into adulthood. While we did not find evidence of altered GABA release from SST neurons onto other neurons within the circuit, we found a complementary reduction in layer II/III pyramidal neuron excitability immediately after binge drinking; however, this hypoexcitability rebounded towards increased pyramidal neuron activity in adulthood in females, suggesting long-term homeostatic adaptations in this circuit. Together, this suggests that binge drinking during key developmental timepoints leads to permanent changes in PL microcircuitry function, which may have broad behavioral implications.

neuroscience↗

Somatostatin Neurons in the Bed Nucleus of the Stria Terminalis Play a Sex-Dependent Role in Binge Drinking

Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential. HIGHLIGHTSO_LIChemogenetic activation of BNST SST neurons reduces binge drinking in female but not male mice C_LIO_LIChemogenetic activation of these neurons has no effect on anxiety-like behavior in either sex C_LIO_LIElectrophysiology revealed no clear sex differences in intrinsic excitability BNST SST neurons between males and females C_LIO_LIImaging revealed males had greater overall BNST SST cell numbers than females, but this effect could be explained by normalizing for total BNST volume C_LI

neuroscience↗