dopaminergic system

Neuromodulation of subjective experience

Many psychoactive substances are used with the aim of altering experience, e.g. as analgesics, antidepressants or antipsychotics. These drugs act on specific receptor systems in the brain, including the opioid, serotonergic and dopaminergic systems. In this talk, I will summarise human drug studies targeting opioid receptors and their role for human experience, with focus on the experience of pain, stress, mood, and social connection. Opioids are only indicated for analgesia, due to their potential to cause addiction. When these regulations occurred, other known effects were relegated to side effects. This may be the cause of the prevalent myth that opioids are the most potent painkillers, despite evidence from head-to-head trials, Cochrane reviews and network meta-analyses that opioids are not superior to non-opioid analgesics in the treatment of acute or chronic non-cancer pain. However, due to the variability and diversity of opioid effects across contexts and experiences, some people under some circumstances may indeed benefit from prolonged treatment. I will present data on individual differences in opioid effects due to participant sex and stress induction. Understanding the effects of these commonly used medications on other aspects of the human experience is important to ensure correct use and to prevent unnecessary pain and addiction risk.

Dynamic dopaminergic signaling probabilistically controls the timing of self-timed movements

Human movement disorders and pharmacological studies have long suggested molecular dopamine modulates the pace of the internal clock. But how does the endogenous dopaminergic system influence the timing of our movements? We examined the relationship between dopaminergic signaling and the timing of reward-related, self-timed movements in mice. Animals were trained to initiate licking after a self-timed interval following a start cue; reward was delivered if the animal’s first lick fell within a rewarded window (3.3-7 s). The first-lick timing distributions exhibited the scalar property, and we leveraged the considerable variability in these distributions to determine how the activity of the dopaminergic system related to the animals’ timing. Surprisingly, dopaminergic signals ramped-up over seconds between the start-timing cue and the self-timed movement, with variable dynamics that predicted the movement/reward time, even on single trials. Steeply rising signals preceded early initiation, whereas slowly rising signals preceded later initiation. Higher baseline signals also predicted earlier self-timed movement. Optogenetic activation of dopamine neurons during self-timing did not trigger immediate movements, but rather caused systematic early-shifting of the timing distribution, whereas inhibition caused late-shifting, as if dopaminergic manipulation modulated the moment-to-moment probability of unleashing the planned movement. Consistent with this view, the dynamics of the endogenous dopaminergic signals quantitatively predicted the moment-by-moment probability of movement initiation. We conclude that ramping dopaminergic signals, potentially encoding dynamic reward expectation, probabilistically modulate the moment-by-moment decision of when to move. (Based on work from Hamilos et al., eLife, 2021).

Differential coding of valence and expectation signals across the dopaminergic system

COSYNE 2025

Assessment of motor performance and nigrostriatal dopaminergic system in L66 mice with frontotemporal degeneration-like tauopathy

Asymmetrical influence of the superior colliculus on the midbrain dopaminergic system via ipsilateral direct excitation and contralateral indirect inhibition relied by the rostromedial tegmental nucleus

Binge-eating alters dopaminergic system, reduces anxiety, and increases impulsivity in periadolescent rats

Focus on the mouse insular cortex: in vivo single-unit recordings during anxiety assays and mapping of the dopaminergic system

A forced physical exercise maintenance program as a model for selective manipulation of the dopaminergic system in adolescent rats

Orexin neuromodulation of the dopaminergic system: behavioral correlates and mechanistic insights

A Traslational Study of The Cerebellar Neuronal Dopaminergic System and its links to the Midbrain Dopaminergic Nuclei and Role in Dopamine-related Brain Disorders

Impact of a highly potent and long-acting cocaine hydrolase on recovery of dopaminergic system after cocaine exposure

FENS Forum 2024

Involvement of the dopaminergic system in two distinct regions of the hippocampus in the stress-induced antinociceptive responses in rats

FENS Forum 2024

The involvement of the dopaminergic system in tumbling behavior of pigeons (Columba livia)

FENS Forum 2024