Topic: GRABDA

Temporal-difference reinforcement learning proposed that dopamine signals reward prediction errors, which backpropagate scalar values inherent in rewards to reward-predictive cues. This theory is supported by studies of dopamine activity in cue-reward learning, where a reward-paired cue acquires the dopamine response previously evoked by the reward. However, dopamine has recently been implicated in backward reward-cue learning. Specifically, a recent optogenetic study used a backward conditioning paradigm, where sensory cues are presented following the delivery of rewards, and showed that inhi

Working memory (WM) is the brain process for actively maintaining information during a short delay period. Dopamine is known to strongly modulate WM, but its temporal specificity in modulating WM and its related neuronal activity remain elusive. Here we report that dopamine modulates olfactory WM behavior in a bi-directional and timing-dependent manner in head-fixed mice performing a delay-paired association task. In vivo imaging of dopamine levels in the medial prefrontal cortex (mPFC) by a newly developed GPCR-activation-based-dopamine sensor (GRABDA) revealed phasic elevation of mPFC dopami

To learn and remember where to find reward in an environment, the brain’s spatial map must be updated by reward predictive information. This spatial memory process relies on the hippocampus. As reward locations are learned, hippocampal place cells shift or ‘remap’ their firing fields to overrepresent the reward location at the population level[1]. These shifts are thought to rely on dopaminergic input, which when manipulated can alter the hippocampal representation as well as the animal’s memory of reward[2-4]. Yet the dynamics of dopamine release in the hippocampus under normal learning condi

Substance use disorders (SUD) has a significant impact on human wellbeing and carries a high economic cost in the modern world. Astrocytes are known to participate in all major aspects of brain functions by regulating extracellular levels of neuroactive molecules. Notably, astrocytes were previously shown to critically adjust levels of dopamine in the prefrontal cortex (PFC) through astroglial vesicular monoamine transporter 2 (aVMAT2). Our recent data also indicate aVMAT2 expression in the nucleus accumbens (NAcc)., As SUD engages common neural pathways involved in natural reward processing i

Brain cognitive performances are typically thought to fully rely on neurons. Yet, recent research has shown that the other major cell type of the brain, the astrocyte, actively influence information processing. Astrocytes are indeed involved in the modulation of neuronal circuit activities underlying behavior, by regulating extracellular concentrations of ion and neurotransmitters. We have previously found that astrocytes control dopamine levels in the prefrontal cortex, thereby modulating synaptic transmission and plasticity. Dopamine release can occur physically, responding to specific stimu

The prefrontal cortex plays a crucial role in cognitive functions such as decision making, planning, and working memory. It is subjected to strong monoaminergic neuromodulation, particularly by dopamine from the VTA. While dopamine innervations in the prefrontal cortex are sparse, recent research indicates that the vesicular dopamine transporter VMAT2 in astrocytes contributes to dopaminergic homeostasis in the prefrontal cortex. Here we hypothesized that astrocytes could provide a shuttle mechanism through which appropriate tonic levels of dopamine would be redistributed across the prefrontal