About

Ron Keiflin received his B.S. in Neuroscience from the University of Strasbourg, France, and his Ph.D. in Neuroscience from the University of Bordeaux, France. His postdoctoral work, conducted at UC San Francisco and at Johns Hopkins University, demonstrated the causal role of phasic dopamine signals in reward prediction learning. He joined the faculty of UC Santa Barbara in January 2019 as an Assistant Professor in the Psychological & Brain Sciences department. His research investigates the neural bases of associative learning and decision-making, and how these processes are altered in psychiatric disorders such as addiction and schizophrenia. His lab combines behavioral tasks in rodents with modern neuroscience tools, including fiberphotometry, optogenetics, and chemogenetics, to monitor and manipulate neural activity in specific circuits, particularly focusing on midbrain dopamine neurons and their influence on striatal and prefrontal networks. The goal of his research is to define the principles governing behavior and the neural circuit dynamics underlying learning and decision-making.

Research topics

• Artificial Intelligence
• Computer Science
• Neuroscience
• Psychology
• Biology
• Anatomy
• Social psychology

Selected publications

• Cocaine disrupts hidden states in the brain

  eLife · 2026-04-08

  articleOpen accessSenior author

  Cocaine use disrupts the encoding of abstract states in the orbitofrontal cortex.

  PublisherDOI

• Orbitofrontal circuits for context-gated reward predictions

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-06

  articleOpen accessSenior authorCorresponding

  The orbitofrontal cortex (OFC) is essential for the contextual regulation of reward predictions, yet the circuit mechanisms underlying this function remain unclear. Here, we dissected the roles of two major OFC efferent pathways —projections to the central dorsal striatum (CDS) and the mediodorsal thalamus (MDT)— in contextual regulation. Male and female rats performed a context-dependent discrimination task in which the reward-predictive status of two auditory target cues (X and Y) was determined by a visual contextual cue (A). Using temporally precise optogenetic inhibition of OFC terminals, we found that silencing OFC→CDS profoundly disrupted contextual gating, virtually abolishing the negatively gated component (A:Y− / Y+) while producing modest effects on the positively gated component (A:X+ / X−). In contrast, OFC→MDT inhibition produced modest and qualitatively distinct effects, characterized by a generalized increase in responding in context A and a decrease in context noA. These effects were reproduced in a connectionist model in which context influenced predictions either additively (via elemental representations) or by acting as a gatekeeper (via configural cue/context representations). Disrupting the configural pathway mimicked OFC→CDS silencing, whereas amplifying additive contextual inputs replicated OFC→MDT inhibition. Together, these findings reveal complementary circuit mechanisms through which the OFC shapes context-appropriate reward seeking.

  PublisherDOI

• Author response: Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

  2024-07-11

  peer-reviewOpen accessSenior author

  Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+ / DARK: X− / LIGHT: Y− / DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

  PublisherDOI

• Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

  eLife · 2024-05-30

  preprintOpen accessSenior author

  Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+ / DARK: X− / LIGHT: Y− / DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

  PublisherDOI

• Partially dissociable roles of the Orbitofrontal cortex and dorsal Hippocampus in context-dependent (hierarchical) reward prediction and contextual inference in learning

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-06-19

  preprintOpen accessSenior authorCorresponding

  Reward cues are often ambiguous; what is good in one context is not necessarily good in another context. To solve this ambiguity, animals form hierarchical associations in which the context acts as a gatekeeper in the retrieval of the appropriate cue-evoked memory, ensuring context-appropriate behavior. These hierarchical associative structures also influence future learning by promoting the formation of new context-dependent associations (leading to the inference of context-dependency for new associations). The orbitofrontal cortex (OFC) and the dorsal hippocampus (DH) are both proposed to encode a “cognitive map” that includes the representation of hierarchical, context-dependent, associations. However the causal role of the OFC and DH in the different functional properties of hierarchical associations remains controversial. Here we used chemogenetic inactivations, in rats, to examine the role of OFC and DH in 1) the contextual regulation of performance, and 2) the contextual learning bias conferred by hierarchical associations. We show that OFC is required for both manifestations of hierarchical associations. In contrast, DH contribution appears limited to the contextual learning bias. This study provides novel insight into the different functional properties of context-dependent hierarchical associations, and establishes the OFC as a critical orchestrator of these different contextual effects.

  PublisherOA PDFDOI

• Reviewer #1 (Public Review): Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

  2024-05-30

  peer-reviewOpen accessSenior author

  Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+ / DARK: X− / LIGHT: Y− / DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

  PublisherDOI

• Author response: Sex differences in discrimination behavior and orbitofrontal engagement during context-gated reward prediction

  2024-07-24

  peer-reviewOpen accessSenior author

  Rodent model of context-dependent discrimination reveals sex-biased tradeoff between speed of acquisition and robustness of contextual control over cue-elicited reward seeking, linked to orbitofrontal cortex activation.

  PublisherDOI

• Reviewer #2 (Public Review): Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

  2024-05-30

  peer-reviewOpen accessSenior author

  Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+ / DARK: X− / LIGHT: Y− / DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

  PublisherDOI

• Author response: Sex Differences in Discrimination Behavior and Orbitofrontal Engagement During Context-Gated Reward Prediction

  2024-05-30

  peer-reviewOpen accessSenior author

  Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+ / DARK: X− / LIGHT: Y− / DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the orbitofrontal cortex, and might have implications for our understanding of sex differences in psychiatric disorders.

  PublisherDOI

• Partially dissociable roles of the orbitofrontal cortex and dorsal hippocampus in context-dependent hierarchical associations

  Current Biology · 2024 · 5 citations

  Senior authorCorresponding
  • Biology
  • Neuroscience
  • Anatomy
  PublisherDOI

Frequent coauthors

• Patricia H. Janak

  Johns Hopkins Medicine

  20 shared

• Jose Chavira

  University of California, Santa Barbara

  16 shared

• Sophie Peterson

  University of California, Santa Barbara

  16 shared

• Brenda Wu

  University of California, Santa Barbara

  14 shared

• Amanda Maheras

  University of California, Santa Barbara

  14 shared

• Elizabeth E. Steinberg

  4 shared

• Heather J. Pribut

  University of Maryland, College Park

  4 shared

• Josiah R. Boivin

  Massachusetts Institute of Technology

  4 shared

Education

• B.S., Neuroscience

  University of Strasbourg

• Ph.D., Neuroscience

  University of Bordeaux