Biology subjects

Steffensen, S. C.

Publications and source records attributed to Steffensen, S. C..

3 recordsLinked to original sources

bioRxiv2026

Microglial and Neuronal Cross-talk in the Nucleus Accumbens

Microglia are the brain's resident immune cells and rapidly migrate toward sites of neuronal stress and neurotransmitter imbalance. The molecular cues directing microglia movement remain poorly understood, particularly in brain regions involved in reward processing, including the nucleus accumbens (NAc). Dopamine (DA) dysregulation and production of reactive oxygen species (ROS) are hallmarks of substance use disorders and neurodegenerative diseases. Dopamine and adenosine triphosphate (ATP) are co-released in the NAc, but the effects of ROS on ATP/DA co-transmission and microglia surveillance remain unknown. Using multiphoton imaging in brain slices with GFP-labeled microglia, we found that ATP consistently and non-selectively drives microglia chemoattraction, whereas DA chemoattraction only occurs in a subset of microglia through D1 but not D2 receptor activation. Microglia enter a reactive state via LPS, and LPS results in enhanced DA/ATP release measured via fast scan cyclic voltammetry. ROS production also transitions microglia to a reactive state, but inhibits DA release, with mixed effects on ATP release. These findings identify ATP- and DA-mediated mechanisms for NAc microglia chemoattraction and opposing immune dysregulation (via LPS or ROS) of DA terminal function.

neuroscience↗

bioRxiv2026

Shared mechanisms of dopamine and ATP transmission in the nucleus accumbens

Dopamine (DA) neurons of the midbrain project throughout the striatum, including the nucleus accumbens core (NAc) and are thought to co-release ATP with DA from vesicles. The mechanisms of evoked NAc ATP release and clearance and their relationship to exocytotic DA transmission are largely unexplored and the focus of the present work. Using fast scan cyclic voltammetry (FSCV), we measured simultaneous ATP and DA transmission in response to pharmacological manipulations of release and reuptake cellular machinery. ATP transmission is tightly coupled to that of DA, though ATP release concentrations are typically smaller. Manipulations that increase DA transmission (increased release via 4-aminopyridine Kv channel blockade or decreased uptake via cocaine) also increase ATP transmission, though to a smaller extent. Blocking DA vesicular packaging (reserpine) or action potentials (lidocaine), results in attenuated DA and ATP release. Interestingly, reserpine or lidocaine can result in completely abolished DA release, but not a complete prevention in ATP release, suggesting a secondary source for ATP transmission thats not dependent on DA terminals. Both transmitters were reduced to a similar extent following nAChR blockade, demonstrating that nAChR activation regulates ATP in addition to DA. Surprisingly, cocaine inhibition of DATs reduced clearance for both ATP and DA, which correlated with one another when cocaine concentration was highest. There was also a strong relationship between the effect of cocaine on release of ATP and DA. As the first FSCV study to examine evoked NAc ATP release, this paper bridges prior work to confirm the strong association between ATP and DA in the mesolimbic circuit and identifies unexpected overlap in mechanisms regulating their transmission. Our results contribute novel evidence of both vesicular and non-vesicular ATP release in the NAc and demonstrate that extracellular ATP is a modulator of DA terminal function.

neuroscience↗

bioRxiv2021

Nociceptive stimuli activate the hypothalamus-habenula circuit to inhibit the mesolimbic reward system

Nociceptive signals interact with various regions of the brain, including those involved in physical sensation, reward, cognition, and emotion. Emerging evidence points to a role of nociception in the modulation of the mesolimbic reward system. The mechanism by which nociception affects dopamine (DA) signaling and reward is unclear. The lateral hypothalamus (LH) and the lateral habenula (LHb) receive somatosensory inputs and are structurally connected with the mesolimbic DA system. Here we show that the LH-LHb pathway is necessary for nociceptive modulation of this system. Our extracellular single-unit recordings and head-mounted microendoscopic calcium imaging revealed that nociceptive stimulation by tail-pinch excited LHb and LH neurons, which was inhibited by chemical lesion of the LH. Tail-pinch decreased extracellular DA release in the nucleus accumbens ventrolateral shell, which was blocked by disruption of the LH. Furthermore, tail-pinch attenuated cocaine-induced locomotor activity, 50-kHz ultrasonic vocalizations and reinstatement of cocaine-seeking behavior, which was inhibited by chemogenetic silencing of the LH-LHb pathway. Our findings suggest that nociceptive stimulation recruits the LH-LHb pathway to inhibit mesolimbic DA system and drug reinstatement.

neuroscience↗