Dr. Rodriguez utilizes an interdisciplinary approach to finding treatment for patients suffering from compulsive behaviors such as Obsessive-Compulsive Disorder (OCD) and hoarding disorder. Her numerous studies aim to gain understanding of these behaviors at multiple levels of analysis (from molecule to behavior).
On the OCD front, Dr. Rodriguez is focusing on the ability of ketamine, an NMDA receptor antagonist, to quickly and effectively quell obsessive thoughts. She is using a variety of imaging techniques to observe the effects of ketamine on neurotransmitter systems and brain activity in human patients, as well as investigating the benefits of combining ketamine administration with therapy. She is also investigating the use of intranasal drug delivery for fast-acting treatments.
Dr. Rodriguez research interests include understanding the underlying brain mechanisms involved in hoarding behaviors and how these differ from normal collecting behavior. In addition, in order to help individuals with hoarding disorder, Dr. Rodriguez is working with government agencies to test a novel treatment intervention consisting of skills-based group treatment targeting hoarding behaviors.
In addition to her research, Dr. Rodriguez also works to educate the public about compulsive behaviors and anxiety disorders by contributing to The Huffington Post on topics such as clutter, ketamine, and the science of fear.
Assistant Professor, Psychiatry and Behavioral Sciences
Member, Stanford Neurosciences Institute
Director, Translational OCD Research Program (2015 - Present)
Director, Stanford Hoarding Disorders Research Program (2015 - Present)
Director, Rodriguez Lab (2015 - Present)
Honors & Awards
Florence Irving Scholar, Irving Institute for Clinical and Translational Research (2014)
Robins/Guze Award, American Psychopathological Association (2014)
Neuropsychopharmacology Editor's Award for Tranformative Original Report (NEATOR) Award, American College of Neuropsychopharmacology (2014)
Harold Amos Medical Faculty Development Award, Robert Wood Johnson Foundation (2015)
Boards, Advisory Committees, Professional Organizations
Vice Chairperson, Council on Research, American Psychiatric Association (APA) (2016 - Present)
Scientific Program Committee, American Psychiatric Association (APA) (2016 - Present)
Director, Executive Board of the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) (2015 - Present)
Chair, OCD Practice Guidelines Work Group, Anxiety and Depression Association of America (ADAA) (2015 - 2016)
Co-Chair, American College of Neuropsychopharmacology (ACNP) Minority Task Force (2016 - Present)
Secretary General, American Society of Hispanic Psychiatry (2012 - 2014)
Laughlin Fellow, American College of Psychiatrists (2007 - 2009)
BS, Harvard University, Computer Science (1996)
PhD, Harvard Medical School, Neuroscience (2004)
MD, Harvard Medical School and Massachusetts Institute of Technology, Health Sciences and Technology (2004)
Residency, Columbia University-NYSPI, Psychiatry (2008)
Board Certification, Psychiatry, American Board of Psychiatry and Neurology (2009)
Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).
Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients.A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson's chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable.14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables.Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.
View details for DOI 10.1017/S1092852917000177
View details for PubMedID 28300008
Acceptability of treatments and services for individuals with hoarding behaviors
JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS
2016; 11: 1-8
To explore the acceptability of currently available treatments and services for individuals who self-report hoarding behaviors.Between 10/2013 and 8/2014, participants were invited to complete an online survey that provided them descriptions of eleven treatments and services for hoarding behaviors and asked them to evaluate their acceptability using quantitative (0 [not at all acceptable] -10 [completely acceptable]) Likert scale ratings. The a priori definition of acceptability for a given resource was an average Likert scale score of six or greater. Two well-validated self-report measures assessed hoarding symptom severity: the Saving Inventory-Revised and the Clutter Image Rating Scale.Two hundred and seventy two participants who self-reported having hoarding behaviors completed the questionnaire. Analyses focused on the 73% of responders (n=203) who reported clinically significant hoarding behaviors (i.e., Saving Inventory-Revised scores of ≥40). The three most acceptable treatments were individual cognitive behavioral therapy (6.2 ±3.1 on the Likert scale), professional organizing service (6.1 ±3.2), and use of a self-help book (6.0 ±3.0).In this sample of individuals with self-reported clinically significant hoarding behaviors (n=203), only 3 out of 11 treatments and services for hoarding were deemed acceptable using an a priori score. While needing replication, these findings indicate the need to design more acceptable treatments and services to engage clients and maximize treatment outcomes for hoarding disorder.
View details for DOI 10.1016/j.jocrd.2016.07.001
View details for Web of Science ID 000391774100001
View details for PubMedID 28163996
- Open-Label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. journal of clinical psychiatry 2016; 77 (5): 688-689
An investigation of the role of intolerance of uncertainty in hoarding symptoms.
Journal of affective disorders
2016; 193: 208-214
Hoarding disorder (HD) is a common, debilitating mental illness and public health burden. Understanding the factors that contribute to hoarding is critical for identifying treatment targets. As a relatively new diagnostic entity, this research remains in its initial stages. Intolerance of uncertainty (IU) is thought to be a vulnerability factor for generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD), and may also be relevant to HD. We investigated the possible association between IU and hoarding in two sets of analyses.First, we administered self-report measures of IU and hoarding symptoms to unscreened undergraduate students (N=456) and used regressions to probe their association controlling for relevant covariates. Second, in a clinical sample, we compared IU across groups of patients with HD (N=26), GAD (N=26), OCD (N=51), other anxiety disorders (N=91) and healthy controls (N=29).In the student sample, IU predicted hoarding symptoms above and beyond relevant covariates, including hoarding-related beliefs. In the clinical sample, HD patients evidenced greater IU relative to healthy individuals and the mixed anxiety group, and comparable levels of IU to the GAD and OCD groups.This study relied exclusively on self-report questionnaires and a cross-sectional design.IU is associated with hoarding behavior and, as we discuss, conceptual models might benefit from the study of IU as a potentially contributing factor. Directions for future research are discussed.
View details for DOI 10.1016/j.jad.2015.12.047
View details for PubMedID 26773912
- Can exposure-based CBT extend the effects of intravenous ketamine in obsessive-compulsive disorder? an open-label trial. journal of clinical psychiatry 2016; 77 (3): 408-409
- Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of Concept. The American journal of psychiatry 2016; 173 (12): 1239–41
Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder.
Human brain mapping
Deficits in attention have been implicated in Obsessive-Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs-fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN-SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN-SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN-SN networks that subserve attentional processes and this effect of OCD on DMN-SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN-SN connectivity may represent a trans-diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN-SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.23408
View details for PubMedID 27659299
A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder.
2016; 21 (3): 320–27
The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.
View details for DOI 10.1038/mp.2015.83
View details for PubMedID 26283639
In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept
2015; 233 (2): 141-147
We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy ((1)H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology.
View details for DOI 10.1016/j.pscychresns.2015.06.001
View details for Web of Science ID 000359313300010
View details for PubMedID 26104826
- Bridging the Divide: Advances and Challenges in Understanding the Impact of Race and Ethnicity on the Mental Health of Older Adults AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY 2015; 23 (6): 545-547
Six-Month Outcomes From a Randomized Trial Augmenting Serotonin Reuptake Inhibitors With Exposure and Response Prevention or Risperidone in Adults With Obsessive-Compulsive Disorder
JOURNAL OF CLINICAL PSYCHIATRY
2015; 76 (4): 440-446
To compare outcomes after 6-month maintenance treatment of adults diagnosed with obsessive-compulsive disorder (OCD) based on DSM-IV criteria who responded to acute treatment with serotonin reuptake inhibitors (SRIs) augmented by exposure and response prevention (EX/RP) or risperidone.A randomized trial was conducted at 2 academic sites from January 2007 through December 2012. In the acute phase, 100 patients on therapeutic SRI dose with at least moderate OCD severity were randomized to 8 weeks of EX/RP, risperidone, or pill placebo. Responders entered the 6-month maintenance phase, continuing the augmentation strategy they received acutely (n = 30 EX/RP, n = 8 risperidone). Independent evaluations were conducted every month. The main outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).Intent-to-treat analyses indicated that, after 6-month maintenance treatment, EX/RP yielded OCD outcomes that were superior to risperidone (Y-BOCS = 10.95 vs 18.70; t40 = 2.76, P = .009); more patients randomized to EX/RP met response criteria (Y-BOCS decrease ≥ 25%: 70% vs 20%; P < .001) and achieved minimal symptoms (Y-BOCS ≤ 12: 50% vs 5%; P < .001). During maintenance, OCD severity decreased slightly in both conditions (Y-BOCS decrease = 2.2 points, P = .020). Lower Y-BOCS at entry to maintenance was associated with more improvement in both conditions (r38 = 0.57, P < .001).OCD patients taking SRIs who responded to acute EX/RP or risperidone maintained their gains over 6-month maintenance. Because EX/RP patients improved more during acute treatment than risperidone-treated patients, and both maintained their gains during maintenance, EX/RP yielded superior outcomes 6 months later. The findings that 50% of patients randomized to EX/RP had minimal symptoms at 6-month maintenance, a rate double that of prior studies, suggests that EX/RP maintenance helps maximize long-term outcome.ClinicalTrials.gov identifier: NCT00389493.
View details for DOI 10.4088/JCP.14m09044
View details for Web of Science ID 000354997500025
View details for PubMedID 25375780
- Canned art. The Lancet. Psychiatry 2015; 2 (8): 690–91
Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder A Randomized Clinical Trial
2013; 70 (11): 1190-1198
Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.clinicaltrials.gov Identifier: NCT00389493.
View details for DOI 10.1001/jamapsychiatry.2013.1932
View details for Web of Science ID 000328948700011
View details for PubMedID 24026523
Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
2013; 38 (12): 2475-2483
Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
View details for DOI 10.1038/npp.2013.150
View details for Web of Science ID 000325710200016
View details for PubMedID 23783065
Prevalence and Correlates of Difficulty Discarding Results From a National Sample of the US Population
JOURNAL OF NERVOUS AND MENTAL DISEASE
2013; 201 (9): 795-801
This study presents nationally representative data on the prevalence and the correlates of difficulty discarding, a behavior described in many psychiatric disorders, including a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, called hoarding disorder. Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions, a national sample of the US population (N=43,093). Difficulty discarding worn-out/worthless items (assessed by a single item) and diagnoses of psychiatric disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The prevalence of difficulty discarding worn-out/worthless items in the general population was 20.6%. Difficulty discarding strongly correlated with axis I and axis II disorders, level of impairment, and use of mental health services. Difficulty discarding worn-out/worthless items is a common behavior that can be associated with various forms of psychopathology. When reported in a clinical setting, it may signal that careful assessment is needed to clarify diagnosis and inform treatment strategies.
View details for DOI 10.1097/NMD.0b013e3182a21471
View details for Web of Science ID 000330375300011
View details for PubMedID 23995036
- Does Extended Release Methylphenidate Help Adults With Hoarding Disorder? A Case Series JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY 2013; 33 (3): 444-447
Public-Academic Partnerships A Rapid Small-Grant Program for Policy-Relevant Research: Motivating Public-Academic Partnerships
2013; 64 (2): 106-108
To help grow a cadre of researchers with the knowledge and skills to pursue topics of great utility to public mental health systems, the director of the Division of Mental Health Services and Policy Research at Columbia University used funding from the New York State Office of Mental Health (OMH) to create a rapid small-grant program called the OMH Policy Scholars Program. This column uses two case examples to describe how this public-academic partnership exposes early-career researchers to the needs and complexities of large public mental health systems while providing them with senior research and policy mentors to help ensure the success of the scholars' projects and oversee their introduction to and work within the public mental health system. This type of collaboration is one model of encouraging early-career psychiatric researchers to pursue policy-relevant research.
View details for DOI 10.1176/appi.ps.201200519
View details for Web of Science ID 000327260400007
View details for PubMedID 23370621
Prevalence of Hoarding Disorder in Individuals at Potential Risk of Eviction in New York City A Pilot Study
JOURNAL OF NERVOUS AND MENTAL DISEASE
2012; 200 (1): 91-94
This study estimated the prevalence of hoarding disorder (HD) in individuals seeking help from Eviction Intervention Services Housing Research Center (EIS), a not-for-profit community organization in New York City (NYC) that aids clients with housing problems including eviction. One hundred fifteen EIS clients were screened for HD. The prevalence of HD among those seeking help from EIS was 22% (clinician-rated) and 23% (self-rated), which is nearly 5 to 10 times greater than the rate of hoarding (2% to 5%) in the general population. Of individuals seeking help from EIS who met the criteria for HD (n = 25), 32% were currently in legal eviction proceedings (i.e., threatened with imminent eviction), 44% had a history of previous legal eviction proceedings, and 20% had been evicted from their home one or more times, yet only 48% were currently seeking mental health treatment. Almost a quarter of individuals seeking help for housing problems from a community eviction prevention organization met the criteria for HD; only about half of these individuals were receiving mental health treatment. Future studies are needed to determine whether HD treatment can reduce the risk of eviction and homelessness in NYC.
View details for DOI 10.1097/NMD.0b013e31823f678b
View details for Web of Science ID 000298636600013
View details for PubMedID 22210369
- From Clutter to Modern Art: A Chinese Artist's Perspective on Hoarding Behaviors AMERICAN JOURNAL OF PSYCHIATRY 2011; 168 (12): 1248-1248
- Rapid Resolution of Obsessions After an Infusion of Intravenous Ketamine in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY 2011; 72 (4): 567-569
- Minocycline Augmentation of Pharmacotherapy in Obsessive-Compulsive Disorder: An Open-Label Trial JOURNAL OF CLINICAL PSYCHIATRY 2010; 71 (9): 1247-1249
- Diagnosis and Treatment of a Patient With Both Psychotic and Obsessive-Compulsive Symptoms AMERICAN JOURNAL OF PSYCHIATRY 2010; 167 (7): 754-761
- Personalized Intervention for Hoarders at Risk of Eviction PSYCHIATRIC SERVICES 2010; 61 (2): 205-205
- The Role of Culture in Psychodynamic Psychotherapy: Parallel Process Resulting From Cultural Similarities Between Patient and Therapist AMERICAN JOURNAL OF PSYCHIATRY 2008; 165 (11): 1402-1406
Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6
2005; 48 (6): 933-947
The lower rhombic lip (LRL) is a germinal zone in the dorsal hindbrain productive of tangentially migrating neurons, streaming extramurally (mossy fiber neurons) or intramurally (climbing fiber neurons). Here we show that LRL territory, operationally defined by Wnt1 expression, is parceled into molecular subdomains predictive of cell fate. Progressing dorsoventrally, Lmx1a and Gdf7 expression identifies the primordium for hindbrain choroid plexus epithelial cells; Math1, for mossy fiber neurons; and immediately ventral to Math1 yet within Wnt1(+) territory, a climbing fiber primordium dominated by Ngn1-expressing cells. Elimination of Pax6 results in expansion of this Ngn1(+) progenitor pool and reduction in the Math1(+) pool, with accompanying later enlargement of the climbing fiber nucleus and reductions in mossy fiber nuclei. Pax6 loss also disrupts Msx expression cell-nonautonomously, suggesting Pax6 may influence LRL progenitor identity indirectly through potentiating BMP signaling. These studies suggest that underlying the diversity and proportions of fates produced by the LRL is a precise suborganization regulated by Pax6.
View details for DOI 10.1016/j.neuron.2005.11.031
View details for Web of Science ID 000234301700010
View details for PubMedID 16364898
Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation
2003; 35 (1): 70-75
The hindbrain roof plate and choroid plexus are essential organizing centers for inducing dorsal neuron fates and sustaining neuron function. To map the formation of these structures, we developed a broadly applicable, high resolution, recombinase-based method for mapping the fate of cells originating from coordinates defined by intersecting combinations of expressed genes. Using this method, we show that distinct regions of hindbrain roof plate originate from discrete subdomains of rhombencephalic neuroectoderm expressing Wnt1; that choroid plexus, a secretory epithelium important for patterning later-formed hindbrain structures and maintaining neuron function, derives from the same embryonic primordium as the hindbrain roof plate; and that, unlike the floor plate, these dorsal organizing centers develop in a patterned, segmental manner, built from lineage-restricted compartments. Our data suggest that the roof plate and choroid plexus may be formed of functional units that are capable of differentially organizing the generation of distinct neuronal cell types at different axial levels.
View details for DOI 10.1038/ng1228
View details for Web of Science ID 000185018500013
View details for PubMedID 12923530
Switching on lineage tracers using site-specific recombination.
Methods in molecular biology (Clifton, N.J.)
2002; 185: 309-334
View details for PubMedID 11768998
Origin of the precerebellar system
2000; 27 (3): 475-486
The precerebellar system provides the principal input to the cerebellum and is essential for coordinated motor activity. Using a FLP recombinase-based fate mapping approach, we provide direct evidence in the mouse that this ventral brainstem system derives from dorsally located rhombic neuroepithelium. Moreover, by fate mapping at the resolution of a gene expression pattern, we have uncovered an unexpected subdivision within the precerebellar primordium: embryonic expression of Wnt1 appears to identify the class of precerebellar progenitors that will later project mossy fibers from the brainstem to the cerebellum, as opposed to the class of precerebellar neurons that project climbing fibers. Differential gene expression therefore appears to demarcate two populations within the precerebellar primordium, grouping progenitors by their future type of axonal projection and synaptic partner rather than by final topographical position.
View details for Web of Science ID 000089601300012
View details for PubMedID 11055431
- High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP NATURE GENETICS 2000; 25 (2): 139-140
Short-wave cone signal in the red-green detection mechanism
1998; 38 (6): 813-826
Previous work shows that the red-green (RG) detection mechanism is highly sensitive, responding to equal and opposite long-wave (L) and middle-wave (M) cone contrast signals. This mechanism mediates red-green hue judgements under many conditions. We show that the RG detection mechanism also receives a weak input from the short-wave (S) cones that supports the L signal and equally opposes M. This was demonstrated with a pedestal paradigm, in which weak S cone flicker facilitates discrimination and detection of red-green flicker. Also, a near-threshold +S cone flash facilitates detection of red flashes and inhibits green flashes, and a near-threshold -S cone flash facilitates detection of green flashes and inhibits red flashes. The S contrast weight in RG is small relative to the L and M contrast weights. However, a comparison of our results with other studies suggests that the strength of the absolute S cone contrast contribution to the RG detection mechanism is 1/4 to 1/3 the strength of the S contribution to the blue-yellow (BY) detection mechanism. Thus, the S weight in RG is a significant fraction of the S weight in BY. This has important implications for the 'cardinal' color mechanisms, for it predicts that for detection or discrimination, the mechanisms limiting performance do not lie on orthogonal M-L and S axes within the equiluminant color plane.
View details for Web of Science ID 000072768100005
View details for PubMedID 9624432