Biology subjects

Siemsen, B.

Publications and source records attributed to Siemsen, B..

3 recordsLinked to original sources

bioRxiv2021

Chemogenetic Inhibition of Corticostriatal Circuits Reduces Cued Reinstatement of Methamphetamine Seeking

Methamphetamine (meth) causes enduring changes within the medial prefrontal cortex (mPFC) and the nucleus accumbens (NA). Projections from the mPFC to the NA have a distinct dorsal-ventral distribution, with the prelimbic (PL) mPFC projecting to the NAcore, and the infralimbic (IL) mPFC projecting to the NAshell. Inhibition of these circuits has opposing effects on cocaine relapse. Inhibition of PL-NAcore reduces cued reinstatement of cocaine seeking and IL-NAshell inhibition reinstates cocaine seeking. Meth, however, exhibits a different profile, as pharmacological inhibition of either the PL or IL decrease cued reinstatement of meth-seeking. The potentially opposing roles of the PL-NAcore and IL-NAshell projections remain to be explored in the context of cued meth seeking. Here we used an intersectional viral vector approach that employs a retrograde delivery of Cre from the NA and Cre-dependent expression of DREADD in the mPFC, in both male and female rats to inhibit or activate these parallel pathways. Inhibition of the PL-NAcore circuit reduced cued reinstatement of meth seeking under short and long-access meth self-administration and after withdrawal with and without extinction. Inhibition of the IL-NAshell also decreased meth cued reinstatement. Activation of the parallel circuits was without an effect. These studies show that inhibition of the PL-NAcore or the IL-NAshell circuits can inhibit reinstated meth seeking. Thus, the neural circuitry mediating cued reinstatement of meth seeking is similar to cocaine in the dorsal, but not ventral, mPFC-NA circuit.

neuroscience↗

bioRxiv2019

Amperometric measurements of cocaine cue and novel context-evoked glutamate and nitric oxide release in the nucleus accumbens core

Cue-induced reinstatement of cocaine seeking after self-administration (SA) and extinction relies on glutamate release in the nucleus accumbens core (NAcore), which in turn activates neuronal nitric oxide synthase (nNOS) interneurons. Nitric oxide (NO) is required for structural plasticity in NAcore medium spiny neurons (MSNs), as well as cued cocaine seeking. However, NO release in the NAcore during reinstatement has yet to be directly measured. Further, the temporal relationship between glutamate release, and the induction of a NO response also remains unknown. Using wireless amperometric recordings in awake behaving rat, we quantified the magnitude and temporal dynamics of novel context- and cue-induced reinstatement-evoked glutamate and NO release in the NAcore. We found that re-exposure to cocaine-conditioned stimuli following SA and extinction increased extracellular glutamate, leading to release of NO in the NAcore. In contrast, exposing drug-naive rats to a novel context led to a lower magnitude rise in glutamate in the NAcore relative to cue-induced reinstatement. Interestingly, novel context exposure evoked a higher magnitude NO response relative to cue-induced reinstatement. Despite differences in magnitude, novel context evoked-NO release in the NAcore was also temporally delayed when compared to glutamate. These results demonstrate a dissociation between the magnitude of cocaine cue- and novel context-evoked glutamate and NO release in the NAcore, yet similarity in the temporal dynamics of their release. Together, these data contribute to a greater understanding of the relationship between glutamate and NO, two neurotransmitters implicated in encoding the valence of distinct contextual stimuli.

neuroscience↗

bioRxiv2019

Chronic Intermittent Ethanol Exposure Differentially Alters Microglial Morphology in the Prelimbic Cortex and Nucleus Accumbens Core

Accumulating evidence has linked pathological changes associated with chronic alcohol exposure to neuroimmune signaling mediated by microglia. Prior characterization of the microglial structure-function relationship demonstrates that alterations in activity states occur concomitantly with reorganization of cellular architecture. Accordingly, gaining a better understanding of microglial morphological changes associated with ethanol exposure will provide valuable insight into how neuroimmune signaling may contribute to ethanol-induced reshaping of neuronal function. Here we have used Iba-1-staining combined with high-resolution confocal imaging and 3D reconstruction to examine microglial structure in the prelimbic (PL) cortex and nucleus accumbens (NAc) in male Long-Evans rats. Rats were either sacrificed at peak withdrawal following 14 days of exposure to chronic intermittent ethanol (CIE) or 48 hours after exposure to the immune activator lipopolysaccharide (LPS). LPS exposure resulted in dramatic structural reorganization of microglia in the PL cortex; including increased soma volume, overall cellular volume, and branching complexity. In comparison, CIE exposure was associated with a subtle increase in somatic volume and differential effects on microglia processes, which were largely absent in the NAc. These data reveal that microglial activation following a neuroimmune challenge with LPS or exposure to chronic alcohol exhibit distinct morphometric profiles and brain-region dependent specificity.

neuroscience↗