About

Stephan Lammel is an Associate Professor of Neuroscience at the University of California, Berkeley. His research focuses on midbrain dopamine circuits involved in reward-based behaviors and the pathological changes associated with addiction, depression, and schizophrenia. As a faculty member in the Neuroscience Department, he contributes to understanding the neural mechanisms underlying these complex behaviors and mental health conditions, advancing the field through his investigations into circuit systems and behavioral neuroscience.

Research topics

• Neuroscience
• Psychology
• Biology
• Developmental psychology
• Cognitive psychology

Selected publications

• Changes in neurotensin signalling drive hedonic devaluation in obesity

  Universität Zürich, ZORA · 2025-05-01

  articleOpen accessSenior author

  Calorie-rich foods, particularly those that are high in fat and sugar, evoke pleasure in both humans and animals. However, prolonged consumption of such foods may reduce their hedonic value, potentially contributing to obesity. Here we investigated this phenomenon in mice on a chronic high-fat diet (HFD). Although these mice preferred high-fat food over regular chow in their home cages, they showed reduced interest in calorie-rich foods in a no-effort setting. This paradoxical decrease in hedonic feeding has been reported previously, but its neurobiological basis remains unclear. We found that in mice on regular diet, neurons in the lateral nucleus accumbens (NAcLat) projecting to the ventral tegmental area (VTA) encoded hedonic feeding behaviours. In HFD mice, this behaviour was reduced and uncoupled from neural activity. Optogenetic stimulation of the NAcLat→VTA pathway increased hedonic feeding in mice on regular diet but not in HFD mice, though this behaviour was restored when HFD mice returned to a regular diet. HFD mice exhibited reduced neurotensin expression and release in the NAcLat→VTA pathway. Furthermore, neurotensin knockout in the NAcLat and neurotensin receptor blockade in the VTA each abolished optogenetically induced hedonic feeding behaviour. Enhancing neurotensin signalling via overexpression normalized aspects of diet-induced obesity, including weight gain and hedonic feeding. Together, our findings identify a neural circuit mechanism that links the devaluation of hedonic foods with obesity.

  PublisherDOI

• Changes in neurotensin signalling drive hedonic devaluation in obesity

  Nature · 2025-03-26 · 15 citations

  articleOpen accessSenior author

  Abstract Calorie-rich foods, particularly those that are high in fat and sugar, evoke pleasure in both humans and animals 1 . However, prolonged consumption of such foods may reduce their hedonic value, potentially contributing to obesity 2–4 . Here we investigated this phenomenon in mice on a chronic high-fat diet (HFD). Although these mice preferred high-fat food over regular chow in their home cages, they showed reduced interest in calorie-rich foods in a no-effort setting. This paradoxical decrease in hedonic feeding has been reported previously 3–7 , but its neurobiological basis remains unclear. We found that in mice on regular diet, neurons in the lateral nucleus accumbens (NAcLat) projecting to the ventral tegmental area (VTA) encoded hedonic feeding behaviours. In HFD mice, this behaviour was reduced and uncoupled from neural activity. Optogenetic stimulation of the NAcLat→VTA pathway increased hedonic feeding in mice on regular diet but not in HFD mice, though this behaviour was restored when HFD mice returned to a regular diet. HFD mice exhibited reduced neurotensin expression and release in the NAcLat→VTA pathway. Furthermore, neurotensin knockout in the NAcLat and neurotensin receptor blockade in the VTA each abolished optogenetically induced hedonic feeding behaviour. Enhancing neurotensin signalling via overexpression normalized aspects of diet-induced obesity, including weight gain and hedonic feeding. Together, our findings identify a neural circuit mechanism that links the devaluation of hedonic foods with obesity.

  PublisherOA PDFDOI

• Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns

  Neuron · 2025-01-14 · 11 citations

  articleOpen access

  Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood. Using our cell-specific D1R photo-agonist, we find that D1R activation in D1-expressing neurons in the dorsomedial striatum is sufficient to reinforce preceding neural firing patterns in defined ensembles of layer 5 cortico-striatal neurons of the mouse motor cortex. The reinforcement is cumulative and time dependent, with an optimal effect when D1R activation follows the selected neural pattern after a short interval. Our results show that D1R activation in striatal neurons can selectively reinforce cortical activity patterns, independent of a behavioral outcome or a reward, crucially contributing to the fundamental mechanisms that support cognitive functions like learning, memory, and decision-making.

  PublisherDOI

• Rebound Bursting Selectively Enables Fast Dynamics in Dopamine Midbrain Neurons Projecting to the Dorsolateral Striatum

  Journal of Neuroscience · 2025-09-26 · 3 citations

  articleOpen access

  Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson’s disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. Here, we show that DLS-projecting DA neurons in the substantia nigra (SN) possess a unique biophysical profile allowing immediate 10-fold accelerations in discharge frequency via rebound bursting. By using a combination of in vitro patch-clamp recordings in projection-defined DA SN subpopulations from adult male mice and developing matching projection-specific computational models, we demonstrate that a strong interaction of Ca v 3 and SK channels specific for DLS-projecting Aldh1a1–positive DA SN (DLS-DA) neurons controls the gain of fast rebound bursting, while K v 4 and HCN channels mediate timing of rebound excitability. In addition, GIRK channels activated by D2 and GABA B receptors prevent rebound bursting in these DLS-DA neurons. Furthermore, our in vivo patch-clamp recordings and matching in vivo computational models provide evidence that these unique rebound properties might be preserved in the intact brain, where they might endow specific computational properties well suited for the generation of fast DA dynamics present in DLS.

  PublisherOA PDFDOI

• State and rate-of-change encoding in parallel mesoaccumbal dopamine pathways

  Nature Neuroscience · 2024-01-11 · 53 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• A computational analysis of mouse behavior in the sucrose preference test

  Nature Communications · 2023-04-27 · 60 citations

  articleOpen accessSenior author

  The sucrose preference test (SPT) measures the relative preference of sucrose over water to assess hedonic behaviors in rodents. Yet, it remains uncertain to what extent the SPT reflects other behavioral components, such as learning, memory, motivation, and choice. Here, we conducted an experimental and computational decomposition of mouse behavior in the SPT and discovered previously unrecognized behavioral subcomponents associated with changes in sucrose preference. We show that acute and chronic stress have sex-dependent effects on sucrose preference, but anhedonia was observed only in response to chronic stress in male mice. Additionally, reduced sucrose preference induced by optogenetics is not always indicative of anhedonia but can also reflect learning deficits. Even small variations in experimental conditions influence behavior, task outcome and interpretation. Thus, an ostensibly simple behavioral task can entail high levels of complexity, demonstrating the need for careful dissection of behavior into its subcomponents when studying the underlying neurobiology.

  PublisherOA PDFDOI

• Dopamine release and negative valence gated by inhibitory neurons in the laterodorsal tegmental nucleus

  Neuron · 2023-07-26 · 23 citations

  article
  PublisherDOI

• Head-mounted central venous access during optical recordings and manipulations of neural activity in mice

  Nature Protocols · 2023-12-06

  reviewOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Transient food insecurity during the juvenile-adolescent period affects adult weight, cognitive flexibility, and dopamine neurobiology

  Current Biology · 2022-07-20 · 41 citations

  articleOpen access

  A major challenge for neuroscience, public health, and evolutionary biology is to understand the effects of scarcity and uncertainty on the developing brain. Currently, a significant fraction of children and adolescents worldwide experience insecure access to food. The goal of our work was to test in mice whether the transient experience of insecure versus secure access to food during the juvenile-adolescent period produced lasting differences in learning, decision-making, and the dopamine system in adulthood. We manipulated feeding schedules in mice from postnatal day (P)21 to P40 as food insecure or ad libitum and found that when tested in adulthood (after P60), males with different developmental feeding history showed significant differences in multiple metrics of cognitive flexibility in learning and decision-making. Adult females with different developmental feeding history showed no differences in cognitive flexibility but did show significant differences in adult weight. We next applied reinforcement learning models to these behavioral data. The best fit models suggested that in males, developmental feeding history altered how mice updated their behavior after negative outcomes. This effect was sensitive to task context and reward contingencies. Consistent with these results, in males, we found that the two feeding history groups showed significant differences in the AMPAR/NMDAR ratio of excitatory synapses on nucleus-accumbens-projecting midbrain dopamine neurons and evoked dopamine release in dorsal striatal targets. Together, these data show in a rodent model that transient differences in feeding history in the juvenile-adolescent period can have significant impacts on adult weight, learning, decision-making, and dopamine neurobiology.

  PublisherDOI

• Mesoaccumbal Dopamine Heterogeneity: What Do Dopamine Firing and Release Have to Do with It?

  Annual Review of Neuroscience · 2022-02-28 · 93 citations

  reviewOpen accessSenior author

  Ventral tegmental area (VTA) dopamine (DA) neurons are often thought to uniformly encode reward prediction errors. Conversely, DA release in the nucleus accumbens (NAc), the prominent projection target of these neurons, has been implicated in reinforcement learning, motivation, aversion, and incentive salience. This contrast between heterogeneous functions of DA release versus a homogeneous role for DA neuron activity raises numerous questions regarding how VTA DA activity translates into NAc DA release. Further complicating this issue is increasing evidence that distinct VTA DA projections into defined NAc subregions mediate diverse behavioral functions. Here, we evaluate evidence for heterogeneity within the mesoaccumbal DA system and argue that frameworks of DA function must incorporate the precise topographic organization of VTA DA neurons to clarify their contribution to health and disease.

  PublisherOA PDFDOI

Recent grants

• Circuit-specific mechanisms of reward and aversion in ventral tegmental area dopamine neurons

  NIH · $4.0M · 2017–2027

• A multi-level investigation into the effects of chronic stress on lateral habenula circuitry

  NIH · $1.9M · 2017–2023

Frequent coauthors

• Johannes W. de Jong

  University of California, Berkeley

  11 shared

• Hongbin Yang

  Hangzhou Seventh Peoples Hospital

  7 shared

• Robert C. Malenka

  6 shared

• Christine Liu

  Massachusetts Eye and Ear Infirmary

  6 shared

• Karl Deisseroth

  Stanford University

  6 shared

• James R. Peck

  University of California, Berkeley

  5 shared

• Byung Kook Lim

  University of California, San Diego

  5 shared

• Yichen Zhu

  The Third Affiliated Hospital of Zhejiang Chinese Medical University

  5 shared

Education

• Postdoctoral Scholar, Psychiatry and Behavioral Sciences

  Stanford University School of Medicine

• PhD

  Philipps-Universität Marburg