Pablo E. Castillo, M.D., Ph.D.

Professor, Dominick P. Purpura Department of Neuroscience
Professor, Department of Psychiatry and Behavioral Sciences
Harold and Muriel Block Chair in Neuroscience

Area of research

Synaptic transmission and plasticity in the mammalian brain. Synaptic dysfunction in experimental models of Alzheimer's disease, epilepsy, autism, schizophrenia and drug abuse.

pablo.castillo@einsteinmed.edu

Phone

718-430-3263

Location

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

Professional Interests

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.

Selected Publications

Nasrallah K, Berthoux C, Hashimotodani Y, Chávez AE, Gulfo MC, Luján R, Castillo PE. (2024) Retrograde adenosine/A2A receptor signaling facilitates excitatory synaptic transmission and seizures. Cell Rep. (in press).

Rangel-Sandoval C, Soula M, Li WP, Castillo PE, Hunt DL. (2024) NMDAR-mediated activation of pannexin1 channels contributes to the detonator properties of hippocampal mossy fiber synapses. iScience. 27(5):109681. doi: 10.1016/j.isci.2024.109681.

Gulfo MC, Lebowitz JJ, Ramos C, Hwang DW, Nasrallah K, Castillo PE. (2023) Dopamine D2 receptors in hilar mossy cells regulate excitatory transmission and hippocampal function. Proc Natl Acad Sci U S A. 120(50):e2307509120. doi: 10.1073/pnas.2307509120.

Das S, Lituma PJ, Castillo PE, Singer RH. (2023) Maintenance of a short-lived protein required for long-term memory involves cycles of transcription and local translation. Neuron. 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 U S A. 119(32):e2201151119. doi: 10.1073/pnas.2201151119.

Lituma PJ, Singer RH, Das S, Castillo PE. (2022) Real-time imaging of Arc/Arg3.1 transcription ex vivo reveals input-specific immediate early gene dynamics. Proc Natl Acad Sci U S A. 119(38):e2123373119. doi: 10.1073/pnas.2123373119.

Monday HR, Kharod SC, Yoon YJ, Singer RH, Castillo PE (2022) Presynaptic FMRP and local protein synthesis support structural and functional plasticity of glutamatergic axon terminals. Neuron (in press) 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) Activation of Extrasynaptic Kainate Receptors Drives Hilar Mossy Cell Activity. 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) Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus. Proc Natl Acad Sci U S A. 118(4):e2017590118. doi: 10.1073/pnas.2017590118

Monday, H. R., Bourdenx, M., Jordan, B. A. & Castillo, P. E. (2020) CB1 receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination. 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.

Monday HR, Younts TJ, Castillo PE. (2018) Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease. Annu Rev Neurosci. 41:299-322.

Hashimotodani Y, Nasrallah K, Jensen KR, Chávez AE, Carrera D, Castillo PE. (2107) LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance. Neuron 95:928-9.

Younts TJ, Monday HR, Dudok B, Klein ME, Jordan BA, Katona I, Castillo PE. (2016) Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release. Neuron 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) Selective Dysregulation of Hippocampal Inhibition in the Mouse Lacking Autism Candidate Gene 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 & Castillo PE (2008) Long-term potentiation selectively expressed by NMDA receptors at hippocampal mossy fiber synapses. 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) Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability Neuron 38, 461-72.