Pablo E. Castillo, MD, Ph.D.

Profesor, Dominick P. Purpura Departamento de Neurociencia
Profesor, Departamento de PsiquiatrÃa y Ciencias del Comportamiento
CÃ¡tedra Harold y Muriel Block de Neurociencia

Ãrea de investigaciÃ³n

TransmisiÃ³n sinÃ¡ptica y plasticidad en el cerebro de los mamÃferos. DisfunciÃ³n sinÃ¡ptica en modelos experimentales de enfermedad de Alzheimer, epilepsia, autismo, esquizofrenia y abuso de drogas.

Correo electrÃ³nico

pablo.castillo@einsteinmed.edu

TelÃ©fono

718-430-3263

centro mÃ©dico

Albert Einstein College of Medicine Centro Rose F. Kennedy 1410 Pelham Parkway Sur 701 Bronx, NY 10461

Intereses profesionales

Synaptic transmission underlies every aspect of nervous system function. How we think, feel, act, and learn, all rely on information transfer between nerve cells. The main goal of my research program is to understand how neural activity controls the strength of synaptic connections in the brain -- a process known as synaptic plasticity -- and how dysregulation of this process contributes to brain disease states. To examine synaptic function and gain insights into the mechanisms and functional consequences of synaptic plasticity, we utilize a combination of experimental approaches, including electrophysiology, molecular pharmacology, optogenetic tools, calcium imaging using two-photon laser microscopy, in vivo molecular manipulations that target intracellular signaling and protein expression, in vivo recordings of neuronal activity, and mouse models for various neuropsychiatric and neurodevelopmental disorders, such as Alzheimer’s disease, Parkinson’s disease, epilepsy, autism, and schizophrenia.

Publicaciones Seleccionadas

Nasrallah K, Berthoux C, Hashimotodani Y, Chávez AE, Gulfo MC, Luján R, Castillo PE. (2024) La seÃ±alizaciÃ³n retrÃ³grada del receptor de adenosina/A2A facilita la transmisiÃ³n sinÃ¡ptica excitatoria y las convulsiones. Cell Rep. (en prensa).

Rangel-Sandoval C, Soula M, Li WP, Castillo PE, Hunt DL. (2024) La activaciÃ³n mediada por NMDAR de los canales pannexina1 contribuye a las propiedades detonadoras de las sinapsis de fibras musgosas del hipocampo. iScience. 27(5):109681. doi: 10.1016/j.isci.2024.109681.

Gulfo MC, Lebowitz JJ, Ramos C, Hwang DW, Nasrallah K, Castillo PE. (2023) Los receptores de dopamina D2 en las cÃ©lulas musgosas hiliares regulan la transmisiÃ³n excitatoria y la funciÃ³n del hipocampo. Proc Natl Acad Sci EE.UU. A. 120(50):e2307509120. doi: 10.1073/pnas.2307509120.

Das S, Lituma PJ, Castillo PE, Singer RH. (2023) El mantenimiento de una proteÃna de vida corta necesaria para la memoria a largo plazo implica ciclos de transcripciÃ³n y traducciÃ³n local. Neurona. 111(13):2051-2064.e6. doi: 10.1016/j.neuron.2023.04.005.

Nasrallah K, Frechou MA, Yoon YJ, Persaud S, Gonçalves JT, Castillo PE (2022) Seizure-induced strengthening of a recurrent excitatory circuit in the dentate gyrus is pro-convulsant. Proc Natl Acad Sci EE.UU. A. 119(32):e2201151119. doi: 10.1073/pnas.2201151119.

Lituma PJ, Singer RH, Das S, Castillo PE. (2022) ImÃ¡genes en tiempo real de la transcripciÃ³n de Arc/Arg3.1 ex vivo revelan dinÃ¡mica genÃ©tica temprana inmediata especÃfica de entrada. Proc Natl Acad Sci EE.UU. A. 119(38):e2123373119. doi: 10.1073/pnas.2123373119.

Monday HR, Kharod SC, Yoon YJ, Singer RH, Castillo PE (2022) La FMRP presinÃ¡ptica y la sÃntesis de proteÃnas local apoyan la plasticidad estructural y funcional de las terminales de los axones glutamatÃ©rgicos. Neuron (en prensa) doi: 10.1016/j.neuron.2022.05.024.

Ramos C, Lutzu S, Yamasaki M, Yanagawa Y, Sakimura K, Tomita S, Watanabe M, Castillo PE. (2022) La activaciÃ³n de los receptores de kainato extrasinÃ¡pticos impulsa la actividad de las cÃ©lulas musgosas hiliares. J Neurosci. 42:2872-2884. doi: 10.1523/JNEUROSCI.0922-21.2022.

Lituma PJ, Kwon HB, Alviña K, Luján R, Castillo PE (2021) Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses. eLife 10:e66612. doi: 10.7554/eLife.66612.

Jensen KR, Berthoux C, Nasrallah K, Castillo PE. (2021) MÃºltiples cascadas de seÃ±alizaciÃ³n de cannabinoides suprimen poderosamente la excitaciÃ³n recurrente en el hipocampo. Proc Natl Acad Sci EE.UU. A. 118(4):e2017590118. doi: 10.1073/pnas.2017590118

Monday, HR, Bourdenx, M., Jordan, BA y Castillo, PE (2020) La LTD inhibitoria mediada por el receptor CB1 desencadena la remodelaciÃ³n presinÃ¡ptica a travÃ©s de la sÃntesis de proteÃnas y la ubiquitinaciÃ³n. elife https://doi.org/10.1101/2020.01.09.900464

Weng FJ, Garcia RI, Lutzu S, Alviña K, Zhang Y, Dushko M, Ku T, Zemoura K, Rich D, Garcia-Dominguez D, Hung M, Yelhekar TD, Sørensen AT, Xu W, Chung K, Castillo PE, Lin Y. (2018) Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation. Neuron 97:1137-1152.

Lunes HR, Younts TJ, Castillo PE. (2018) Plasticidad a largo plazo de la liberaciÃ³n de neurotransmisores: mecanismos emergentes y contribuciones a la funciÃ³n y enfermedad del cerebro. AÃ±o Rev Neurosci. 41:299-322.

Hashimotodani Y, Nasrallah K, Jensen KR, Chávez AE, Carrera D, Castillo PE. (2107) La LTP en las sinapsis de cÃ©lulas granulares dentadas y cÃ©lulas musgosas hiliares modula la producciÃ³n del giro dentado aumentando el equilibrio de excitaciÃ³n/inhibiciÃ³n. Neurona 95:928-9.

Younts TJ, Monday HR, Dudok B, Klein ME, Jordan BA, Katona I, Castillo PE. (2016) Se requiere la sÃntesis de proteÃnas presinÃ¡pticas para la plasticidad a largo plazo de la liberaciÃ³n de GABA. Neurona 92:479-492.

Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, Tomita S. (2016) CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron. 2016 Oct 5;92(1):75-83.

Jurgensen S, Castillo PE. (2015) DesregulaciÃ³n selectiva de la inhibiciÃ³n hipocampal en ratones que carecen del gen candidato para autismo CNTNAP2. J Neurosci 35:14681-7.

Hunt DL, Puente N, Grandes P, Castillo PE (2013) Bidirectional NMDA receptor plasticity controls CA3 output and heterosynaptic metaplasticity. Nat Neurosci. 16:1049–59.

Castillo PE, Younts TJ, Chavez AE, Hashimotodani Y (2012) Endocannabinoid signaling and synaptic function. Neuron 76:70–81.

Rodenas-Ruano A, Chávez AE, Cossio MJ, Castillo PE, Zukin RS (2012) REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. Nat Neurosci. 15:1382–90.

Straub C, Hunt DL, Yamasaki M, Kim KS,Watanabe M, Castillo PE, Tomita S. (2011) Unique functions of kainate receptors in the brain are determined by the auxiliary subunit Neto1. Nat Neurosci. 14:866–73.

Castillo PE, Chiu CQ, Carroll RC (2011) Long-term plasticity at inhibitory synapses. Curr. Opin. Neurobiol. 21:328–338.

Chávez AE, Chiu CQ, Castillo PE (2010). TRPV1 activation by endogenous anandamide triggers postsynaptic LTD in dentate gyrus. Nat Neurosci. 13:1511–8.

Heifets BD and Castillo PE (2009) Endocannabinoid signaling and long-term synaptic plasticity. Annu. Rev. Physiol. 71:283–306.

Kwon HB & Castillo PE (2008) Role of glutamate autoreceptors at hippocampal mossy fiber synapses. Neuron. 60, 1082–94.

Kwon HB y Castillo PE (2008) PotenciaciÃ³n a largo plazo expresada selectivamente por los receptores NMDA en las sinapsis de fibras musgosas del hipocampo. Neuron . 57, 108-20.

Heifets BD, Chevaleyre V & Castillo PE (2008) Interneuron activity controls endocannabinoid-mediated presynaptic plasticity through calcineurin. Proc Natl Acad Sci USA. 105, 10250–5.

Chevaleyre V, Heifets BD, Kaeser PS, Sudhof TC & Castillo PE (2007) Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and the active zone protein RIM1alpha. Neuron 54, 801–812.

Chevaleyre V, Takahashi K., Castillo P.E. (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu. Rev. Neurosci. 29:37–75.

Chevaleyre V & Castillo PE (2003) LTD heterosinÃ¡ptica de sinapsis GABAÃ©rgicas del hipocampo: un nuevo papel de los endocannabinoides en la regulaciÃ³n de la excitabilidad Neuron 38, 461-72.