Robert Malenka
Stanford University
H-index: 166
North America-United States
Description
Robert Malenka, With an exceptional h-index of 166 and a recent h-index of 84 (since 2020), a distinguished researcher at Stanford University, specializes in the field of Neuroscience.
His recent articles reflect a diverse array of research interests and contributions to the field:
Striatal dopamine integrates cost, benefit, and motivation
Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice
Intercalated amygdala dysfunction drives extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder
378. Neural Circuit Delineation of (±)-3, 4-methylenedioxymethamphetamine (MDMA)-evoked Sociability and Fear Memory Deficits
MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens
Treatment for loss of control disorders
Orbitofrontal cortex control of striatum leads economic decision-making
Brain-Wide Activity Mapping Reveals a Required Role for the Dorsal Endopiriform Nucleus in MDMA-Evoked Prosocial Behavior
Professor Information
University | Stanford University |
---|---|
Position | Professor of Psychiatry |
Citations(all) | 116422 |
Citations(since 2020) | 29494 |
Cited By | 98125 |
hIndex(all) | 166 |
hIndex(since 2020) | 84 |
i10Index(all) | 301 |
i10Index(since 2020) | 247 |
University Profile Page | Stanford University |
Research & Interests List
Neuroscience
Top articles of Robert Malenka
Striatal dopamine integrates cost, benefit, and motivation
Striatal dopamine (DA) release has long been linked to reward processing, but it remains controversial whether DA release reflects costs or benefits and how these signals vary with motivation. Here, we measure DA release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) while independently varying costs and benefits and apply behavioral economic principles to determine a mouse's level of motivation. We reveal that DA release in both structures incorporates both reward magnitude and sunk cost. Surprisingly, motivation was inversely correlated with reward-evoked DA release. Furthermore, optogenetically evoked DA release was also heavily dependent on sunk cost. Our results reconcile previous disparate findings by demonstrating that striatal DA release simultaneously encodes cost, benefit, and motivation but in distinct manners over different timescales. Future work will be necessary to …
Authors
Neir Eshel,Gavin C Touponse,Allan R Wang,Amber K Osterman,Amei N Shank,Alexandra M Groome,Lara Taniguchi,Daniel F Cardozo Pinto,Jason Tucciarone,Brandon S Bentzley,Robert C Malenka
Journal
Neuron
Published Date
2024/2/7
Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice
Ketamine has anesthetic, analgesic, and antidepressant properties which may involve multiple neuromodulatory systems. In humans, the opioid receptor (OR) antagonist naltrexone blocks the antidepressant effect of ketamine. It is unclear whether naltrexone blocks a direct effect of ketamine at ORs, or whether normal functioning of the OR system is required to realize the full antidepressant effects of treatment. In mice, the effect of ketamine on locomotion, but not analgesia or the forced swim test, was sensitive to naltrexone and was therefore used as a behavioral readout to localize the effect of naltrexone in the brain. We performed whole-brain imaging of cFos expression in ketamine-treated mice, pretreated with naltrexone or vehicle, and identified the central amygdala (CeA) as the area with greatest difference in cFos intensity. CeA neurons expressing both μOR (MOR) and PKCδ were strongly activated by naltrexone but not ketamine, and selectively interrupting MOR function in the CeA either pharmacologically or genetically blocked the locomotor effects of ketamine. These data suggest that MORs expressed in CeA neurons gate behavioral effects of ketamine but are not direct targets of ketamine.
Authors
Matthew B Pomrenze,Sam Vaillancourt,Pierre Llorach,Daniel Ryskamp Rijsketic,Austen B Casey,Nicholas Gregory,Juliana S Salgado,Robert C Malenka,Boris Dov Heifets
Journal
bioRxiv
Published Date
2024
Intercalated amygdala dysfunction drives extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder
Background The avoidance of aversive stimuli due to negative reinforcement learning is critical for survival in real-world environments, which demand dynamic responding to both positive and negative stimuli that often conflict with each other. Individuals with obsessive-compulsive disorder (OCD) commonly exhibit impaired negative reinforcement and extinction, perhaps involving deficits in amygdala functioning. An amygdala subregion of particular interest is the intercalated nuclei of the amygdala (ITC) which has been linked to negative reinforcement and extinction, with distinct clusters mediating separate aspects of behavior. This study focuses on the dorsal ITC cluster (ITCd) and its role in negative reinforcement during a complex behavior that models real-world dynamic decision making. Methods We investigated the impact of ITCd function on negative reinforcement and extinction by applying fiber photometry measurement of GCamp6f signals and optogenetic manipulations during a platform-mediated avoidance task in a mouse model of OCD-like behavior: the Sapap3-null mouse. Results We find impaired neural activity in the ITCd of male and female Sapap3-null mice to the encoding of negative stimuli during platform-mediated avoidance. Sapap3-null mice also exhibit deficits in extinction of avoidant behavior, which is modulated by ITCd neural activity. Conclusions Sapap3-null mice fail to extinguish avoidant behavior in platform-mediated avoidance, due to heightened ITCd activity. This deficit can be rescued by optogenetically inhibiting ITCd during extinction. Together, our results provide insight into the neural mechanisms …
Authors
Robyn St. Laurent,Kelly M Kusche,Anatol C Kreitzer,Robert C Malenka
Journal
bioRxiv
Published Date
2024
378. Neural Circuit Delineation of (±)-3, 4-methylenedioxymethamphetamine (MDMA)-evoked Sociability and Fear Memory Deficits
Background(±)-3, 4-methylenedioxymethamphetamine (MDMA) assisted psychotherapy has demonstrated efficacy for the treatment of PTSD in phase III clinical trials, but the mechanism is poorly understood. Prior work by our lab and others suggests that MDMA elicits a translationally conserved prosocial phenotype in mice, involving serotonergic activity in brain regions involved in fear memory processing, eg, the nucleus accumbens (NAc) and basolateral amygdala (BLA). Here, we hypothesized that impaired threat detection by (±)-MDMA is a common behavioral mechanism driving sociability and altered fear responses, and that these effects are manifested by the same neural circuitry.MethodsTo identify putative components of a neural circuit engaged by MDMA and test their role in fear memory processing and sociability, we used iDISCO+ and lightsheet fluorescence microscopy to map neural activity elicited by …
Authors
Austen Casey,Daniel Ryskamp Rijsketic,Wesley Zhao,Alexander Palmer,Juliana Salgado,Pierre Llorach,Nicholas Wall,Matthew Pomrenze,Robert Malenka,Boris Heifets
Journal
Biological Psychiatry
Published Date
2024/5/15
MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens
MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an “empathogen,” empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia—behavioral tests modeling empathy in mice—with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA’s action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like …
Authors
Ben Rein,Kendall Raymond,Cali Boustani,Sabrena Tuy,Jie Zhang,Robyn St. Laurent,Matthew B Pomrenze,Parnaz Boroon,Boris Heifets,Monique Smith,Robert C Malenka
Journal
Science Advances
Published Date
2024/4/24
Treatment for loss of control disorders
The present invention provides, inter alia, methods, apparatus, and systems useful for ameliorating impulse control disorders known to be extremely disabling and common to many neurological and psychiatric conditions using closed-loop (responsive) neuro stimulation.
Published Date
2024/2/8
Orbitofrontal cortex control of striatum leads economic decision-making
Animals must continually evaluate stimuli in their environment to decide which opportunities to pursue, and in many cases these decisions can be understood in fundamentally economic terms. Although several brain regions have been individually implicated in these processes, the brain-wide mechanisms relating these regions in decision-making are unclear. Using an economic decision-making task adapted for rats, we find that neural activity in both of two connected brain regions, the ventrolateral orbitofrontal cortex (OFC) and the dorsomedial striatum (DMS), was required for economic decision-making. Relevant neural activity in both brain regions was strikingly similar, dominated by the spatial features of the decision-making process. However, the neural encoding of choice direction in OFC preceded that of DMS, and this temporal relationship was strongly correlated with choice accuracy. Furthermore, activity …
Authors
Felicity Gore,Melissa Hernandez,Charu Ramakrishnan,Ailey K Crow,Robert C Malenka,Karl Deisseroth
Journal
Nature Neuroscience
Published Date
2023/9
Brain-Wide Activity Mapping Reveals a Required Role for the Dorsal Endopiriform Nucleus in MDMA-Evoked Prosocial Behavior
BackgroundMDMA assisted psychotherapy is a potentially effective treatment for PTSD. Its efficacy may stem from enhanced feelings of social connection, empathy, and trust during therapy. However, MDMA’s abuse potential warrants understanding its mechanism to develop safer, scalable treatments. Here, we aim to uncover the network of brain regions which selectively produce MDMA’s prosocial effects.MethodsBrain-wide neuronal activity was mapped in C57/Bl6 mice following ip injection of MDMA (7.5 mg/kg) or saline in social (n= 9) and non-social (n= 11) contexts. Brains were immunofluorescently labeled for the immediate early gene cFos, made optically transparent, and imaged via light sheet microscopy. Whole brain volumes were registered to a standard atlas, and a general linear model was applied to construct voxel-wise p-value (<. 05) maps between groups. Multiple comparisons correction was …
Authors
Boris Heifets,Daniel Rijsketic,Juliana Salgado,Nicholas Wall,Grecia Ramirez-Ovalle,Pierre Llorach,Ricardo Lopez,Austen Casey,Tuuli Hietamies,Zahra Rastegar,Daniel Barbosa,Kevin Beier,Robert Malenka
Journal
Biological Psychiatry
Published Date
2023/5/1
Professor FAQs
What is Robert Malenka's h-index at Stanford University?
The h-index of Robert Malenka has been 84 since 2020 and 166 in total.
What are Robert Malenka's top articles?
The articles with the titles of
Striatal dopamine integrates cost, benefit, and motivation
Opioid receptor expressing neurons of the central amygdala gate behavioral effects of ketamine in mice
Intercalated amygdala dysfunction drives extinction deficits in the Sapap3 mouse model of obsessive-compulsive disorder
378. Neural Circuit Delineation of (±)-3, 4-methylenedioxymethamphetamine (MDMA)-evoked Sociability and Fear Memory Deficits
MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens
Treatment for loss of control disorders
Orbitofrontal cortex control of striatum leads economic decision-making
Brain-Wide Activity Mapping Reveals a Required Role for the Dorsal Endopiriform Nucleus in MDMA-Evoked Prosocial Behavior
...
are the top articles of Robert Malenka at Stanford University.
What are Robert Malenka's research interests?
The research interests of Robert Malenka are: Neuroscience
What is Robert Malenka's total number of citations?
Robert Malenka has 116,422 citations in total.