Browsing by Subject "Parvalbumin"

Now showing 1 - 3 of 3
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    EphB2 Signaling Is Implicated in Astrocyte-Mediated Parvalbumin Inhibitory Synapse Development
    (Society for Neuroscience, 2024-11-06) Sutley-Koury, Samantha N.; Taitano-Johnson, Christopher; Kulinich, Anna O.; Farooq, Nadia; Wagner, Victoria A.; Robles, Marissa; Hickmott, Peter W.; Santhakumar, Vijayalakshmi; Mimche, Patrice N.; Ethell, Iryna M.; Dermatology, School of Medicine
    Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch-clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV→PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV→PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.
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    MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling
    (Wiley, 2016-03) Collins, Stuart A.; Huff, Courtney; Chiaia, Nicolas; Gudelsky, Gary A.; Yamamoto, Bryan K.; Department of Pharmacology and Toxicology, IU School of Medicine
    MDMA is a widely abused psychostimulant which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA. Administration of MDMA into the dentate gyrus of rats increased PGE2 concentrations which was prevented by coadministration of MDL100907, a 5HT2A receptor antagonist. MDMA-induced increases in extracellular glutamate were inhibited by local administration of SC-51089, an inhibitor of the EP1 prostaglandin receptor. Systemic administration of SC-51089 during injections of MDMA prevented the decreases in parvalbumin interneurons observed 10 days later. The loss of parvalbumin immunoreactivity after MDMA exposure coincided with a decrease in paired-pulse inhibition and afterdischarge threshold in the dentate gyrus. These changes were prevented by inhibition of EP1 and 5HT2A receptors during MDMA. Additional experiments revealed an increased susceptibility to kainic acid-induced seizures in MDMA treated rats which could be prevented with SC51089 treatments during MDMA exposure. Overall, these findings suggest that 5HT2A receptors mediate MDMA-induced PGE2 signaling and subsequent increases in glutamate. This signaling mediates parvalbumin cell losses as well as physiologic changes in the dentate gyrus, suggesting that the lack of the inhibition provided by these neurons increases the excitability within the dentate gyrus of MDMA treated rats.
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    Sex Differences in Risk and Resilience: Stress Effects on the Neural Substrates of Emotion and Motivation
    (Society for Neuroscience, 2018-10-31) Wellman, Cara L.; Bangasser, Debra A.; Bollinger, Justin L.; Coutellier, Laurence; Logrip, Marian L.; Moench, Kelly M.; Urban, Kimberly R.; Psychology, School of Science
    Risk for stress-sensitive psychopathologies differs in men and women, yet little is known about sex-dependent effects of stress on cellular structure and function in corticolimbic regions implicated in these disorders. Determining how stress influences these regions in males and females will deepen our understanding of the mechanisms underlying sex-biased psychopathology. Here, we discuss sex differences in CRF regulation of arousal and cognition, glucocorticoid modulation of amygdalar physiology and alcohol consumption, the age-dependent impact of social stress on prefrontal pyramidal cell excitability, stress effects on the prefrontal parvalbumin system in relation to emotional behaviors, contributions of stress and gonadal hormones to stress effects on prefrontal glia, and alterations in corticolimbic structure and function after cessation of chronic stress. These studies demonstrate that, while sex differences in stress effects may be nuanced, nonuniform, and nonlinear, investigations of these differences are nonetheless critical for developing effective, sex-specific treatments for psychological disorders.