Determining the role of localized dopamine signals in learning

Neuromodulators like dopamine are crucial for learning, driving synaptic changes in neurons, and shaping behavior. Furthermore, dysfunction in dopamine signaling is a hallmark of almost all psychiatric disorders. Traditionally, dopamine was thought to broadcast diffuse signals across broad brain regions. However, emerging evidence points to a more targeted mechanism, where dopamine acts on specific neurons engaged in behaviorally relevant tasks. This proposal raises a critical question: How does a widely distributed neuromodulator like dopamine contribute to precise, neuron-specific learning? This project will explore how dopamine shapes learning in sparse cortical populations. We will use two-photon microscopy and genetically encoded sensors to simultaneously track dopamine release and neuronal activity in real-time as mice perform a neuroprosthetic control task. We will use this task because it allows us to directly identify the neurons that drive behavior, providing a unique opportunity to examine whether dopamine signals are more focused on task-relevant neurons. We will measure both dopamine release and the activity of specific neurons involved in behavior to determine whether dopamine shapes learning at a single neuron level or across broader networks, and what type of information can be conveyed by dopamine signals at different levels of spatial resolution. This study will help us better understand the brain mechanisms underlying learning by revealing fundamental mechanisms of how dopamine modulates neural circuits. Our results will help us understand how disruptions in these processes contribute to conditions like depression, schizophrenia, and addiction, which involve pathological learning. This research could lead to more targeted therapies focusing on dopamine-related brain circuits, ultimately offering better treatment options for people with cognitive dysfunction and maladaptive behavioral patterns. Project Number: 1R21MH141410-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Nuria Vendrell Llopis (+1 co-PI) | Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM, AL | Award Amount: $409,750 | Activity Code: R21 | Study Section: Learning, Memory and Decision Neuroscience Study Section[LMDN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11215762