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Schluter, O. M.

Publications and source records attributed to Schluter, O. M..

2 recordsLinked to original sources

Investigate c-Fos changes in genetically identified amygdala neurons after mild footshock stress

The amygdala is a key brain region that processes stress-related inputs to reshape future behaviors. The lateral amygdala (LA), basolateral amygdala (BLA), and central amygdala (CeA) are important subregions that mediate different aspects of stress experiences from receiving sensory input to memory formation and behavioral responding. The principal neurons in these regions are glutamatergic pyramidal neurons, which are genetically separable into two subpopulations, protein phosphatase 1 regulatory subunit 1B-positive (Ppp1r1b, also known as DARPP-32) parvocellular neurons and R-spondin2-positive (Rspo2) magnocellular neurons. Recent studies show that these two subpopulations of amygdala neurons differentially regulate appetitive versus aversive behaviors. The research goal of this study is to explore whether amygdala Ppp1r1b and Rspo2 neurons are transcriptionally activated by moderate stress experience, such that persistent cellular changes are made to influence future functional output of these two subtypes of neurons. To test transcriptional activation, we focused on c-Fos, one of the early genes that are transiently expressed in response to cellular stimulations to regulate downstream gene transcription. Moderate stress was introduced through brief footshocks, with mice without footshock as controls. Between shocked and control mice, we observed similar numbers of Ppp1r1b or Rspo2 neurons per unit area that expressed c-Fos, which was consistent across LA-BLA and CeA. Moreover, in LA-BLA, Ppp1r1b/c-Fos cells consistently outnumber Rspo2/c-Fos cells across treatment conditions, and the reverse is true in CeA. These results suggest that moderate stress experience is not sufficient to induce robust transcriptional alterations in the two key subpopulations of amygdala neurons, and Ppp1r1b versus Rspo2 neuron activities, as measured by c-Fos expression levels, show differential dominance in amygdala subregions.

neuroscience↗

Cocaine triggers glial-mediated synaptogenesis

Synaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, 2{delta}-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of 2{delta}-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-2{delta}-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.

neuroscience↗