Contact
Biomedical Research Center251 Bayview Boulevard
Suite 200
Baltimore, MD 21224
Email: Hugo.Tejeda@nih.gov
Education
Ph.D. University of Maryland School of Medicine
Research Interests
Hugo Tejeda graduated with a double major in Biological Sciences and Psychology from the University of Texas at El Paso in 2008 and conducted research in the laboratory of Dr. Laura O’Dell. He completed his Ph.D. in Neuroscience at the University of Maryland School of Medicine and at NIDA in 2013 under the mentorship Drs. Patricio O’Donnell and Toni Shippenberg. Hugo became a post-doctoral fellow in the Bonci laboratory at NIDA in 2013. In the fall of 2018 he will move to NIMH to head the Unit on Neuromodulation and Synaptic Integration at NIMH as a Stadtman Principal Investigator.
His research interests are in understanding how the brain utilizes neuromodulation in motivational and emotional neural circuits to process information and orchestrate behavior. He is also interested in identifying plastic changes in neuromodulation and synaptic integration in these same circuits in animal models of psychiatric disorders to elucidate novel therapeutic targets to treat psychiatric disorders and increase our understanding of conventional therapies.
Publications
Selected Publications
2017
Edwards, Nicholas J; Tejeda, Hugo A; Pignatelli, Marco; Zhang, Shiliang; McDevitt, Ross A; Wu, Jocelyn; Bass, Caroline E; Bettler, Bernhard; Morales, Marisela; Bonci, Antonello
Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. Journal Article
In: Nat Neurosci, vol. 20, no. 3, pp. 438–448, 2017, ISSN: 1546-1726 (Electronic); 1097-6256 (Linking).
@article{Edwards2017,
title = {Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior.},
author = {Nicholas J Edwards and Hugo A Tejeda and Marco Pignatelli and Shiliang Zhang and Ross A McDevitt and Jocelyn Wu and Caroline E Bass and Bernhard Bettler and Marisela Morales and Antonello Bonci},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28114294},
doi = {10.1038/nn.4482},
issn = {1546-1726 (Electronic); 1097-6256 (Linking)},
year = {2017},
date = {2017-03-01},
journal = {Nat Neurosci},
volume = {20},
number = {3},
pages = {438--448},
address = {Intramural Research Program, National Institute on Drug Abuse, US National Institutes of Health, Baltimore, Maryland, USA.},
abstract = {Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch-clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABAB receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABAB receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine.},
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pubstate = {published},
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2015
Tejeda, Hugo A; Hanks, Ashley N; Scott, Liam; Mejias-Aponte, Carlos; Hughes, Zoe A; O'Donnell, Patricio
Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs. Journal Article
In: Neuropsychopharmacology, vol. 40, no. 13, pp. 2856–2864, 2015, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Tejeda:2015aa,
title = {Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs.},
author = {Hugo A Tejeda and Ashley N Hanks and Liam Scott and Carlos Mejias-Aponte and Zoe A Hughes and Patricio O'Donnell},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25971593},
doi = {10.1038/npp.2015.138},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2015},
date = {2015-12-01},
journal = {Neuropsychopharmacology},
volume = {40},
number = {13},
pages = {2856--2864},
address = {Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.},
abstract = {Kappa opioid receptors (KORs) have been implicated in anxiety and stress, conditions that involve activation of projections from the basolateral amygdala (BLA) to the medial prefrontal cortex (mPFC). Although KORs have been studied in several brain regions, their role on mPFC physiology and on BLA projections to the mPFC remains unclear. Here, we explored whether KORs modify synaptic inputs from the BLA to the mPFC using in vivo electrophysiological recordings with electrical and optogenetic stimulation. Systemic administration of the KOR agonist U69,593 inhibited BLA-evoked synaptic responses in the mPFC without altering hippocampus-evoked responses. Intra-mPFC U69,593 inhibited electrical and optogenetic BLA-evoked synaptic responses, an effect blocked by the KOR antagonist nor-BNI. Bilateral intra-mPFC injection of the KOR antagonist nor-BNI increased center time in the open field test, suggesting an anxiolytic effect. The data demonstrate that mPFC KORs negatively regulate glutamatergic synaptic transmission in the BLA-mPFC pathway and anxiety-like behavior. These findings provide a framework whereby KOR signaling during stress and anxiety can regulate the flow of emotional state information from the BLA to the mPFC.},
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2014
Tejeda, Hugo A; O'Donnell, Patricio
Amygdala inputs to the prefrontal cortex elicit heterosynaptic suppression of hippocampal inputs. Journal Article
In: J Neurosci, vol. 34, no. 43, pp. 14365–14374, 2014, ISSN: 1529-2401 (Electronic); 0270-6474 (Linking).
@article{Tejeda:2014aab,
title = {Amygdala inputs to the prefrontal cortex elicit heterosynaptic suppression of hippocampal inputs.},
author = {Hugo A Tejeda and Patricio O'Donnell},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25339749},
doi = {10.1523/JNEUROSCI.0837-14.2014},
issn = {1529-2401 (Electronic); 0270-6474 (Linking)},
year = {2014},
date = {2014-10-22},
journal = {J Neurosci},
volume = {34},
number = {43},
pages = {14365--14374},
address = {Department of Anatomy and Neurobiology, Program in Neuroscience/National Institutes of Health Graduate Partnership Program, and tejedah@nida.nih.gov patricio.odonnell@pfizer.com.},
abstract = {Whereas cooperative communication between the hippocampus (HP) and prefrontal cortex (PFC) is critical for cognitive functions, an antagonistic relationship may exist between the basolateral amygdala (BLA) and PFC during emotional processing. As PFC neurons integrate information from converging excitatory BLA and HP inputs, we explored whether the ability of BLA inputs to evoke feedforward inhibition in the PFC affects converging HP synaptic inputs using in vivo intracellular recordings in anesthetized rats. BLA train stimulation decreased HP synaptic responses in the PFC in vivo. This effect was dependent on the timing of HP-evoked responses and the strength of BLA activation. BLA train stimulation also produced heterosynaptic suppression of responses from the amygdalo-piriform cortex, an associative temporal cortical structure. Heterosynaptic suppression was unidirectional as HP trains failed to modify BLA synaptic responses. These findings provide a mechanism by which BLA activation could decrease PFC neural activity and transiently attenuate the HP influence on PFC function.},
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Cabungcal, Jan Harry; Counotte, Danielle S; Lewis, Eastman; Tejeda, Hugo A; Piantadosi, Patrick; Pollock, Cameron; Calhoon, Gwendolyn G; Sullivan, Elyse; Presgraves, Echo; Kil, Jonathan; Hong, Elliot L; Cuenod, Michel; Do, Kim Q; O'Donnell, Patricio
Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia. Journal Article
In: Neuron, vol. 83, no. 5, pp. 1073–1084, 2014, ISSN: 1097-4199 (Electronic); 0896-6273 (Linking).
@article{Cabungcal:2014aa,
title = {Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia.},
author = {Jan Harry Cabungcal and Danielle S Counotte and Eastman Lewis and Hugo A Tejeda and Patrick Piantadosi and Cameron Pollock and Gwendolyn G Calhoon and Elyse Sullivan and Echo Presgraves and Jonathan Kil and Elliot L Hong and Michel Cuenod and Kim Q Do and Patricio O'Donnell},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25132466},
doi = {10.1016/j.neuron.2014.07.028},
issn = {1097-4199 (Electronic); 0896-6273 (Linking)},
year = {2014},
date = {2014-09-03},
journal = {Neuron},
volume = {83},
number = {5},
pages = {1073--1084},
address = {Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.},
abstract = {Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention.},
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Tejeda, Hugo A; Bonci, Antonello
Shedding UV Light endogenous opioid dependence. Journal Article
In: Cell, vol. 157, no. 7, pp. 1500–1501, 2014, ISSN: 1097-4172 (Electronic); 0092-8674 (Linking).
@article{Tejeda:2014aa,
title = {Shedding UV Light endogenous opioid dependence.},
author = {Hugo A Tejeda and Antonello Bonci},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24949960},
doi = {10.1016/j.cell.2014.06.009},
issn = {1097-4172 (Electronic); 0092-8674 (Linking)},
year = {2014},
date = {2014-06-19},
journal = {Cell},
volume = {157},
number = {7},
pages = {1500--1501},
address = {Synaptic Plasticity Section, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, Baltimore, MD 21224, USA.},
abstract = {Excessive sun tanning can result in addictive behavior. In this issue of Cell, Fell et al. utilize a combination of behavioral pharmacology and transgenic mice to demonstrate that chronic UV light exposure recruits p53 signaling in keratinocytes, subsequently increasing beta-endorphin signaling at opioid receptors, and produces an endogenous opioid-dependent state.},
keywords = {},
pubstate = {published},
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2013
Tejeda, Hugo A; Counotte, Danielle S; Oh, Eric; Ramamoorthy, Sammanda; Schultz-Kuszak, Kristin N; Backman, Cristina M; Chefer, Vladmir; O'Donnell, Patricio; Shippenberg, Toni S
Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission and conditioned place aversion. Journal Article
In: Neuropsychopharmacology, vol. 38, no. 9, pp. 1770–1779, 2013, ISSN: 1740-634X (Electronic); 0893-133X (Linking).
@article{Tejeda:2013aa,
title = {Prefrontal cortical kappa-opioid receptor modulation of local neurotransmission and conditioned place aversion.},
author = {Hugo A Tejeda and Danielle S Counotte and Eric Oh and Sammanda Ramamoorthy and Kristin N Schultz-Kuszak and Cristina M Backman and Vladmir Chefer and Patricio O'Donnell and Toni S Shippenberg},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23542927},
doi = {10.1038/npp.2013.76},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2013},
date = {2013-08-01},
journal = {Neuropsychopharmacology},
volume = {38},
number = {9},
pages = {1770--1779},
address = {Integrative Neuroscience Section, Integrative Neuroscience Branch, National Institute on Drug Abuse, Baltimore, MD, USA. tejedah@nida.nih.gov},
abstract = {Kappa-opioid receptors (KORs) are important for motivation and other medial prefrontal cortex (mPFC)-dependent behaviors. Although KORs are present in the mPFC, their role in regulating transmission in this brain region and their contribution to KOR-mediated aversion are not known. Using in vivo microdialysis in rats and mice, we demonstrate that intra-mPFC administration of the selective KOR agonist U69,593 decreased local dopamine (DA) overflow, while reverse dialysis of the KOR antagonist nor-Binaltorphimine (nor-BNI) enhanced mPFC DA overflow. Extracellular amino-acid levels were also affected by KORs, as U69,593 reduced glutamate and GABA levels driven by the glutamate reuptake blocker, l-trans-pyrrolidine-2,4-dicarboxylate. Whole-cell recordings from mPFC layer V pyramidal neurons revealed that U69,593 decreased the frequency, but not amplitude, of glutamatergic mini EPSPs. To determine whether KOR regulation of mPFC DA overflow was mediated by KOR on DA terminals, we utilized a Cre recombinase-driven mouse line lacking KOR in DA neurons. In these mice, basal DA release or uptake was unaltered relative to controls, but attenuation of mPFC DA overflow by local U69,593 was not observed, indicating KOR acts directly on mPFC DA terminals to locally inhibit DA levels. Conditioning procedures were then used to determine whether mPFC KOR signaling was necessary for KOR-mediated aversion. U69,593-mediated conditioned place aversion was blocked by intra-mPFC nor-BNI microinjection. These findings demonstrate that mPFC KORs negatively regulate DA and amino-acid neurotransmission, and are necessary for KOR-mediated aversion.},
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Dilgen, Jonathan; Tejeda, Hugo A; O'Donnell, Patricio
Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex. Journal Article
In: J Neurophysiol, vol. 110, no. 1, pp. 221–229, 2013, ISSN: 1522-1598 (Electronic); 0022-3077 (Linking).
@article{Dilgen:2013aa,
title = {Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex.},
author = {Jonathan Dilgen and Hugo A Tejeda and Patricio O'Donnell},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23657281},
doi = {10.1152/jn.00531.2012},
issn = {1522-1598 (Electronic); 0022-3077 (Linking)},
year = {2013},
date = {2013-07-01},
journal = {J Neurophysiol},
volume = {110},
number = {1},
pages = {221--229},
address = {Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.},
abstract = {Although interactions between the amygdala and prefrontal cortex (PFC) are critical for emotional guidance of behavior, the manner in which amygdala affects PFC function is not clear. Whereas basolateral amygdala (BLA) output neurons exhibit many characteristics associated with excitatory neurotransmission, BLA stimulation typically inhibits PFC cell firing. This apparent discrepancy could be explained if local PFC inhibitory interneurons were activated by BLA inputs. Here, we used in vivo juxtacellular and intracellular recordings in anesthetized rats to investigate whether BLA inputs evoke feedforward inhibition in the PFC. Juxtacellular recordings revealed that BLA stimulation evoked action potentials in PFC interneurons and silenced most pyramidal neurons. Intracellular recordings from PFC pyramidal neurons showed depolarizing postsynaptic potentials, with multiple components evoked by BLA stimulation. These responses exhibited a relatively negative reversal potential (Erev), suggesting the contribution of a chloride component. Intracellular administration or pressure ejection of the GABA-A antagonist picrotoxin resulted in action-potential firing during the BLA-evoked response, which had a more depolarized Erev. These results suggest that BLA stimulation engages a powerful inhibitory mechanism within the PFC mediated by local circuit interneurons.},
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2012
Tejeda, Hugo A; Natividad, Luis A; Orfila, James E; Torres, Oscar V; O'Dell, Laura E
Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner. Journal Article
In: Psychopharmacology (Berl), vol. 224, no. 2, pp. 289–301, 2012, ISSN: 1432-2072 (Electronic); 0033-3158 (Linking).
@article{Tejeda:2012aa,
title = {Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner.},
author = {Hugo A Tejeda and Luis A Natividad and James E Orfila and Oscar V Torres and Laura E O'Dell},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22659976},
doi = {10.1007/s00213-012-2752-7},
issn = {1432-2072 (Electronic); 0033-3158 (Linking)},
year = {2012},
date = {2012-10-01},
journal = {Psychopharmacology (Berl)},
volume = {224},
number = {2},
pages = {289--301},
address = {Department of Psychology, The University of Texas at El Paso, 500 West University Avenue, El Paso, TX 79968, USA.},
abstract = {RATIONALE: Mechanisms that mediate age differences during nicotine withdrawal are unclear. OBJECTIVE: This study compared kappa-opioid receptor (KOR) activation in naive and nicotine-treated adolescent and adult rats using behavioral and neurochemical approaches to study withdrawal. METHODS: The behavioral models used to assess withdrawal included conditioned place and elevated plus maze procedures. Deficits in dopamine transmission in the nucleus accumbens (NAcc) were examined using microdialysis procedures. Lastly, the effects of KOR stimulation and blockade on physical signs produced upon removal of nicotine were examined in adults. RESULTS: Nicotine-treated adults displayed a robust aversion to an environment paired with a KOR agonist versus naive adults. Neither of the adolescent groups displayed a place aversion. KOR activation produced an increase in anxiety-like behavior that was highest in nicotine-treated adults versus all other groups. KOR activation produced a decrease in NAcc dopamine that was largest in nicotine-treated adults versus all other groups. Lastly, KOR activation facilitated physical signs of withdrawal upon removal of nicotine and KOR blockade reduced this effect. CONCLUSION: Chronic nicotine enhanced the affective, anxiogenic, and neurochemical effects produced by KOR activation in adult rats. Our data suggest that chronic nicotine elicits an increase in KOR function, and this may contribute to nicotine withdrawal since KOR activation facilitated and KOR blockade prevented withdrawal signs upon removal of nicotine. Given that chronic nicotine facilitated the neurochemical effects of KOR agonists in adults but not in adolescents, it is suggested that KOR regulation of mesolimbic dopamine may contribute to age differences in nicotine withdrawal.},
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Loewinger, Gabriel C; Beckert, Michael V; Tejeda, Hugo A; Cheer, Joseph F
In: Neuropharmacology, vol. 62, no. 7, pp. 2192–2201, 2012, ISSN: 1873-7064 (Electronic); 0028-3908 (Linking).
@article{Loewinger:2012aa,
title = {Methamphetamine-induced dopamine terminal deficits in the nucleus accumbens are exacerbated by reward-associated cues and attenuated by CB1 receptor antagonism.},
author = {Gabriel C Loewinger and Michael V Beckert and Hugo A Tejeda and Joseph F Cheer},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22306525},
doi = {10.1016/j.neuropharm.2012.01.013},
issn = {1873-7064 (Electronic); 0028-3908 (Linking)},
year = {2012},
date = {2012-06-01},
journal = {Neuropharmacology},
volume = {62},
number = {7},
pages = {2192--2201},
address = {Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.},
abstract = {Methamphetamine (METH) exposure is primarily associated with deleterious effects to dopaminergic neurons. While several studies have implicated the endocannabinoid system in METH's locomotor, rewarding and neurochemical effects, a role for this signaling system in METH's effects on dopamine terminal dynamics has not been elucidated. Given that CB1 receptor blockade reduces the acute potentiation of phasic extracellular dopamine release from other psychomotor stimulant drugs and that the degree of acute METH-induced increases in extracellular dopamine levels is related to the severity of dopamine depletion, we predicted that pretreatment with the CB1 receptor antagonist rimonabant would reduce METH-induced alterations at dopamine terminals. Furthermore, we hypothesized that administration of METH in environments where reward associated-cues were present would potentiate METH's acute effects on dopamine release in the nucleus accumbens and exacerbate changes in dopamine terminal activity. Fast-scan cyclic voltammetry was used to measure electrically-evoked dopamine release in the nucleus accumbens and revealed markers of compromised dopamine terminal integrity nine days after a single dose of METH. These were exacerbated in animals that received METH in the presence of reward-associated cues, and attenuated in rimonabant-pretreated animals. While these deficits in dopamine dynamics were associated with reduced operant responding on days following METH administration in animals treated with only METH, rimonabant-pretreated animals exhibited levels of operant responding comparable to control. Moreover, dopamine release correlated significantly with changes in lever pressing behavior that occurred on days following METH administration. Together these data suggest that the endocannabinoid system is involved in the subsecond dopaminergic response to METH.},
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