Biology subjects

Reissner, K. J.

Publications and source records attributed to Reissner, K. J..

4 recordsLinked to original sources

bioRxiv2024

Abstinence from cocaine self-administration promotes microglia pruning of astrocytes which drives cocaine-seeking behavior

Rodent drug self-administration leads to compromised ability of astrocytes to maintain glutamate homeostasis within the brains reward circuitry, as well as reductions in surface area, volume, and synaptic colocalization of astrocyte membranes. However, the mechanisms driving astrocyte responses to cocaine are unknown. Here, we report that long-access cocaine self-administration followed by prolonged home cage abstinence results in decreased branching complexity of nucleus accumbens astrocytes, characterized by the loss of peripheral processes. Using a combination of confocal fluorescence microcopy and immuno-gold electron microscopy, we show that alterations in astrocyte structural features are driven by microglia phagocytosis, as labeled astrocyte membranes are found within microglia phagolysosomes. Inhibition of complement C3-mediated phagocytosis using the neutrophil inhibitory peptide (NIF) rescued astrocyte structure and decreased cocaine seeking behavior following cocaine self-administration and abstinence. Collectively, these results provide evidence for microglia pruning of accumbens astrocytes across cocaine abstinence which mediates cocaine craving.

neuroscience↗

bioRxiv2024

Nucleus accumbens astrocytes bidirectionally modulate social behavior

Social behaviors are critical for survival and fitness of a species, and maladaptive social behaviors are frequently associated with neurodevelopmental and psychiatric disorders. As such, the neural circuits and cellular mechanisms driving social behaviors inform critical processes contributing to both health and disease. In particular, the nucleus accumbens (NAc) is a key hub for the integration of both social and non-social information required for successful social interactions and reward motivated behaviors. While astrocytes within the NAc have a recognized role in modulating neural activity, their influence over social behavior is yet undefined. To address this question, we manipulated NAc astrocyte signaling and determined effects on social interactions. NAc core astrocytes bidirectionally influenced social behavior in rats; agonism of astrocyte-specific hM3D(Gq) DREADD receptors increased social interaction time in the social interaction test and increased social preference in the 3-chamber test. Conversely, decreasing intracellular calcium signaling in astrocytes with viral expression of hPMCA reduced both social interaction and social preference in these tests. These results suggest that NAc astrocytes actively participate in the regulation of social behavior and highlight a putative role for astrocytes in disorders characterized by social dysfunction.

neuroscience↗

bioRxiv2024

Investigating cocaine- and abstinence-induced effects on astrocyte gene expression in the nucleus accumbens

In recent years, astrocytes have been increasingly implicated in cellular mechanisms of substance use disorders (SUD). Astrocytes are structurally altered following exposure to drugs of abuse; specifically, astrocytes within the nucleus accumbens (NAc) exhibit significantly decreased surface area, volume, and synaptic colocalization after operant self-administration of cocaine and extinction or protracted abstinence (45 days). However, the mechanisms that elicit these morphological modifications are unknown. The current study aims to elucidate the molecular modifications that lead to observed astrocyte structural changes in rats across cocaine abstinence using astrocyte-specific RiboTag and RNA-seq, as an unbiased, comprehensive approach to identify genes whose transcription or translation change within NAc astrocytes following cocaine self-administration and extended abstinence. Using this method, our data reveal cellular processes including cholesterol biosynthesis that are altered specifically by cocaine self-administration and abstinence, suggesting that astrocyte involvement in these processes is changed in cocaine-abstinent rats. Overall, the results of this study provide insight into astrocyte functional adaptations that occur due to cocaine exposure or during cocaine withdrawal, which may pinpoint further mechanisms that contribute to cocaine-seeking behavior.

neuroscience↗

bioRxiv2022

Abstinence-dependent effects of long-access cocaine self-administration on nucleus accumbens astrocytes are observed in male, but not female rats

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA, 2 hours/day) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here we assess the effects of long-access (LgA, 6 hours/day) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive ([~]40%) reductions in surface area, volume, and postsynaptic colocalization 45 days, but not 24 hours after the last self-administration session. In contrast, no effect of self-administration was observed in astrocytes from female rats. Moreover, no effect of LgA self-administration and abstinence was observed on NAc GLT-1 expression in female rats, an effect that has been well described in males. The results indicate striking and sexually dimorphic effects of abstinence subsequent to LgA self-administration on astrocytes. Taken together, these results indicate a pivotal role of prolonged abstinence in the effects of cocaine self-administration on NAc astrocytes, and extend a growing body of evidence regarding sex differences in the cellular consequences of drug self-administration in the brain.

neuroscience↗