Dr. Boris Heifets, MD, PhD, is a board certified anesthesiologist who specializes in providing anesthesia for neurological surgery. He has practiced at Stanford since 2010.

After completing residency training at Stanford, Dr. Heifets completed fellowship training in neuroanesthesiology, also at Stanford. In addition to treating patients, Dr. Heifets also spends a significant amount of time in the lab, where he is investigating the ways in which psychiatric therapies change the function of neural circuits and synapses in the brain.

Dr. Heifets has a special interest in neural stimulation-based treatments for psychiatric and neurological disorders.

Clinical Focus

  • Neuroanesthesia
  • Anesthesia

Academic Appointments

Honors & Awards

  • K08 Mentored Clinical Scientist Research Career Development Award, National Institute of Mental Health (2017-2021)
  • Mentored Research Training Grant - Basic Science, Foundation for Anesthesia Education and Research (2013-2015)
  • Oustanding Contributions to Anesthesia Research, Department of Anesthesiology, Pain & Perioperative Medicine (2013)
  • Internal Grant Program Award, Department of Anesthesiology, Pain & Perioperative Medicine (2012)

Professional Education

  • Fellowship:Stanford University Dept of Anesthesiology (2016) CA
  • Board Certification: Anesthesia, American Board of Anesthesiology (2014)
  • Residency:Stanford University School of Medicine (2013) CA
  • Internship:Memorial Sloan-Kettering Cancer Center (2010) NY
  • Medical Education:Albert Einstein College of Medicine (2009) NY
  • Fellowship, Stanford Hospital & Clinics, Research (2013)
  • PhD, Albert Einstein College of Medicine, Neuroscience (2009)
  • BS, Yale University, Psychobiology/Neuroscience (1999)

Research & Scholarship

Current Research and Scholarly Interests

Harnessing synaptic plasticity to treat neuropsychiatric disease


All Publications

  • Rabies screen reveals GPe control of cocaine-triggered plasticity. Nature Beier, K. T., Kim, C. K., Hoerbelt, P., Hung, L. W., Heifets, B. D., DeLoach, K. E., Mosca, T. J., Neuner, S., Deisseroth, K., Luo, L., Malenka, R. C. 2017


    Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations.

    View details for DOI 10.1038/nature23888

    View details for PubMedID 28902833

  • MDMA as a Probe and Treatment for Social Behaviors. Cell Heifets, B. D., Malenka, R. C. 2016; 166 (2): 269?72


    MDMA, better known as the recreational drug "ecstasy," is well known for stimulating a feeling of closeness and empathy in its users. We advocate that exploring its mechanism of action could lead to new treatments for psychiatric conditions characterized by impairments in social behavior.

    View details for DOI 10.1016/j.cell.2016.06.045

    View details for PubMedID 27419864

  • Chronic pain. Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens. Science Schwartz, N., Temkin, P., Jurado, S., Lim, B. K., Heifets, B. D., Polepalli, J. S., Malenka, R. C. 2014; 345 (6196): 535-542


    Several symptoms associated with chronic pain, including fatigue and depression, are characterized by reduced motivation to initiate or complete goal-directed tasks. However, it is unknown whether maladaptive modifications in neural circuits that regulate motivation occur during chronic pain. Here, we demonstrate that the decreased motivation elicited in mice by two different models of chronic pain requires a galanin receptor 1-triggered depression of excitatory synaptic transmission in indirect pathway nucleus accumbens medium spiny neurons. These results demonstrate a previously unknown pathological adaption in a key node of motivational neural circuitry that is required for one of the major sequela of chronic pain states and syndromes.

    View details for DOI 10.1126/science.1253994

    View details for PubMedID 25082697

  • Decreased motivation during chronic pain requires long-term depression in the nucleus accumbens SCIENCE Schwartz, N., Temkin, P., Jurado, S., Lim, B. K., Heifets, B. D., Polepalli, J. S., Malenka, R. C. 2014; 345 (6196): 535-542
  • Acute Cardiovascular Toxicity of Low-Dose Intrathecal Ziconotide. Pain medicine (Malden, Mass.) 2013

    View details for DOI 10.1111/pme.12196

    View details for PubMedID 23855951

  • Endocannabinoid Signaling and Long-Term Synaptic Plasticity ANNUAL REVIEW OF PHYSIOLOGY Heifets, B. D., Castillo, P. E. 2009; 71: 283-306


    Endocannabinoids (eCBs) are key activity-dependent signals regulating synaptic transmission throughout the central nervous system. Accordingly, eCBs are involved in neural functions ranging from feeding homeostasis to cognition. There is great interest in understanding how exogenous (e.g., cannabis) and endogenous cannabinoids affect behavior. Because behavioral adaptations are widely considered to rely on changes in synaptic strength, the prevalence of eCB-mediated long-term depression (eCB-LTD) at synapses throughout the brain merits close attention. The induction and expression of eCB-LTD, although remarkably similar at various synapses, are controlled by an array of regulatory influences that we are just beginning to uncover. This complexity endows eCB-LTD with important computational properties, such as coincidence detection and input specificity, critical for higher CNS functions like learning and memory. In this article, we review the major molecular and cellular mechanisms underlying eCB-LTD, as well as the potential physiological relevance of this widespread form of synaptic plasticity.

    View details for DOI 10.1146/annurev.physiol.010908.163149

    View details for Web of Science ID 000264489600014

    View details for PubMedID 19575681

  • Interneuron activity controls endocannabinoid-mediated presynaptic plasticity through calcineurin PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Heifets, B. D., Chevaleyre, V., Castillo, P. E. 2008; 105 (29): 10250-10255


    Retrograde signaling by endocannabinoids (eCBs) mediates a widely expressed form of long-term depression at excitatory and inhibitory synapses (eCB-LTD), involving a reduction in neurotransmitter release. In the hippocampus, eCB-LTD occurs at interneuron (IN)-pyramidal cell (PC) synapses (I-LTD), and its induction requires a presynaptic reduction of cAMP/PKA signaling resulting from minutes of type 1 cannabinoid receptor (CB1R) activation. Although repetitive activity of glutamatergic synapses initiates the eCB mobilization required for I-LTD, it is unclear whether CB1R-containing GABAergic terminals are passive targets of eCBs or whether they actively contribute to induction. Here, we show that the minutes-long induction period for I-LTD may serve as a window to integrate associated spontaneous activity in the same IN receiving the retrograde eCB signal. Indeed, reducing spontaneous IN firing blocked I-LTD, which could be rescued with extra stimulation of inhibitory afferents. Moreover, cell pair recordings showed that a single IN expressed LTD onto a PC only if it was active during eCB signaling. Several methods of disrupting presynaptic Ca(2+) dynamics all blocked I-LTD, strongly suggesting that IN spikes regulate I-LTD by raising Ca(2+) at the nerve terminal. Finally, inhibiting the Ca(2+)-activated phosphatase, calcineurin, fully blocked I-LTD, but blocking another phosphatase did not. Our findings support a model where both CB1R signaling and IN activity shift the balance of kinase and phosphatase activity in the presynaptic terminal to induce I-LTD.

    View details for DOI 10.1073/pnas.0711880105

    View details for Web of Science ID 000257913200072

    View details for PubMedID 18632563

  • Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and RIM1 alpha NEURON Chevaleyre, V., Heifets, B. D., Kaeser, P. S., Sudhof, T. C., Purpura, D. P., Castillo, P. E. 2007; 54 (5): 801-812


    Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by activating presynaptic cannabinoid receptors (i.e., CB1) coupled to G(i/o) protein, can mediate short-term and long-term synaptic depression (LTD). While the presynaptic mechanisms underlying eCB-dependent short-term depression have been identified, the molecular events linking CB1 receptors to LTD are unknown. Here we show in the hippocampus that long-term, but not short-term, eCB-dependent depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We further identify the active zone protein RIM1alpha as a key mediator of both CB1 receptor effects on the release machinery and eCB-dependent LTD in the hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and hippocampus shares major mechanistic features. These findings reveal the signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two crucial brain structures. Furthermore, our results highlight a conserved mechanism of presynaptic plasticity in the brain.

    View details for DOI 10.1016/j.neuron.2007.05.020

    View details for Web of Science ID 000247329900012

    View details for PubMedID 17553427

  • Regulation of regulators of G protein signaling mRNA expression in rat brain by acute and chronic electroconvulsive seizures JOURNAL OF NEUROCHEMISTRY Gold, S. J., Heifets, B. D., Pudiak, C. M., Potts, B. W., Nestler, E. J. 2002; 82 (4): 828-838


    G protein-coupled receptor (GPCR) signaling cascades may be key substrates for the antidepressant effects of chronic electroconvulsive seizures (ECS). To better understand changes in these signaling pathways, alterations in levels of mRNA's encoding regulators of G protein signaling (RGS) protein subtypes-2, -4, -7, -8 and -10 were evaluated in rat brain using northern blotting and in situ hybridization. In prefrontal cortex, RGS2 mRNA levels were increased several-fold 2 h following an acute ECS. Increases in RGS8 mRNA were of lesser magnitude (30%), and no changes were evident for the other RGS subtypes. At 24 h following a chronic ECS regimen, RGS4, -7, and -10 mRNA levels were reduced by 20-30%; only RGS10 was significantly reduced 24 h after acute ECS. Levels of RGS2 mRNA were unchanged 24 h following either acute or chronic ECS. In hippocampus, RGS2 mRNA levels were markedly increased 2 h following acute ECS. More modest increases were seen for RGS4 mRNA expression, whereas levels of the other RGS subtypes were unaltered. At 24 h following chronic ECS, RGS7, -8 and -10 mRNA levels were decreased in the granule cell layer, and RGS7 and -8 mRNA levels were decreased in the pyramidal cell layers. Only RGS8 and -10 mRNA levels were significantly reduced in hippocampus 24 h following an acute ECS. Paralleling neocortex, RGS2 mRNA content was unchanged in hippocampus 24 h following either acute or chronic ECS. In ventromedial hypothalamus, RGS4 mRNA content was increased 24 h following chronic ECS, whereas RGS7 mRNA levels were only increased 24 h following an acute ECS. The increased RGS4 mRNA levels in hypothalamus were significant by 2 h following an acute ECS. These studies demonstrate subtype-, time-, and region-specific regulation of RGS proteins by ECS, adaptations that may contribute to the antidepressant effects of this treatment.

    View details for Web of Science ID 000177369300011

    View details for PubMedID 12358788

  • The effect of scopolamine in older rabbits tested in the 750 ms delay eyeblink classical conditioning procedure INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE Woodruff-Pak, D. S., Green, J. T., Pak, J. T., Heifets, B., Pak, M. H. 2002; 37 (2): 103-113


    We investigated the effect of several doses of scopolamine in older rabbits that were trained for 20 days in the 750 ms delay eyeblink classical conditioning procedure. Our aim was to determine if the scopolamine-injected older rabbit would be a useful model for testing drugs for cognition enhancement in Alzheimer's disease (AD). A total of 39 rabbits with a mean age of 31 months received classical eyeblink conditioning with daily injections of 0.25, 0.75, or 1.5 mg/kg scopolamine hydrobromide or sterile saline vehicle. Doses of 0.75 and 1.5 mg/kg scopolamine significantly impaired acquisition, whereas acquisition was not significantly impaired with 0.25 mg/kg scopolamine. Results exhibit parallels in performance on delay eyeblink classical conditioning between scopolamine-treated older rabbits and human patients diagnosed with AD.

    View details for Web of Science ID 000177491000002

    View details for PubMedID 12186305

  • Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit. Medical science monitor Pak, J., Green, J., Heifets, B., Pak, M., Woodruff-Pak, D. 2002; 8 (4): BR105-12


    The cognition-enhancing drug, nefiracetam, is in Phase III clinical trials to treat memory impairment in Alzheimer's disease (AD). Nefiracetam ameliorates acquisition of delay eyeblink classical conditioning in older rabbits, a form of associative learning with striking behavioral and neurobiological similarities in rabbits and humans. In both species, delay eyeblink conditioning engages the septo-hippocampal cholinergic system and is disrupted when the cholinergic system is antagonized. Delay eyeblink classical conditioning is impaired in normal aging and severely disrupted in AD.To test further the efficacy of nefiracetam in an animal model that mimics some of the neurobiological and behavioral effects present in AD, we tested 56 older rabbits assigned to 7 treatment groups in the 750 ms delay eyeblink conditioning procedure. Older rabbits were injected with 1.5 mg/kg scopolamine to simulate disruption of the cholinergic system in AD. Three doses of nefiracetam (5, 10, or 15 mg/kg) were also injected in older rabbits receiving 1.5 mg/kg scopolamine. Control groups were treated with 1.5 mg/kg scopolamine + vehicle, vehicle alone, or explicitly unpaired presentations of conditioning stimuli and vehicle or 1.5 mg/kg scopolamine + 15 mg/kg nefiracetam.Rabbits injected with 1.5 mg/kg scopolamine alone were impaired, but a dose of 15 mg/kg nefiracetam reversed significantly the behavioral impairment.Nefiracetam had ameliorating effects on a task impaired in AD in an animal model of AD: older rabbits with cholinergic system antagonism.

    View details for PubMedID 11951055

  • Chemical analysis of ecstasy pills JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Baggott, M., Heifets, B., Jones, R. T., Mendelson, J., Sferios, E., Zehnder, J. 2000; 284 (17): 2190-2190

    View details for Web of Science ID 000090052600026

    View details for PubMedID 11056589

  • Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Witkin, J. M., Gasior, M., Heifets, B., Tortella, F. C. 1999; 289 (2): 703-711


    Convulsions associated with cocaine abuse can be life threatening and resistant to standard emergency treatment. Cocaine (75 mg/kg, i. p.) produced clonic convulsions in approximately 90% of male, Swiss-Webster mice. A variety of clinically used antiepileptic agents did not significantly protect against cocaine convulsions (e. g., diazepam and phenobarbital). Anticonvulsants in clinical practice that did significantly protect against convulsion did so only at doses with significant sedative/ataxic effects (e.g., clonazepam and valproic acid). In contrast, functional N-methyl-D-aspartate (NMDA) antagonists all produced dose-dependent and significant protection against the convulsant effects of cocaine. Anticonvulsant efficacy was achieved by blockade of both competitive and noncompetitive modulatory sites on the NMDA receptor complex. Thus, competitive antagonists, ion-channel blockers, polyamine antagonists, and functional blockers of the strychnine-insensitive glycine modulatory site all prevented cocaine seizures. The role of NMDA receptors in the control of cocaine-induced convulsions was further strengthened by the positive correlation between the potencies of noncompetititve antagonists or competitive antagonists to block convulsions and their respective affinities for their specific binding sites on the NMDA receptor complex. Although some NMDA blockers produced profound behavioral side effects at efficacious doses (e.g., noncompetitive antagonists), others (e.g., some low-affinity channel blockers, some competitive antagonists, and glycine antagonists) demonstrated significant and favorable separation between their anticonvulsant and side effect profiles. The present results provide the most extensive evidence to date identifying NMDA receptor blockade as a potential strategy for the discovery of agents for clinical use in averting toxic sequelae from cocaine overdose. Given the literature suggesting a role for these drugs in other areas of drug abuse treatments, NMDA receptor antagonists sit in a unique position as potential therapeutic candidates.

    View details for Web of Science ID 000079857100013

    View details for PubMedID 10215643

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