Faculty Profile

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

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

Areas of Research: Excitatory and inhibitory synaptic transmission and plasticity under physiological and brain disease conditions, such as Alzheimer’s disease, epilepsy, autism, schizophrenia and drug abuse

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. In addition, synapses are extremely dynamic, and activity-dependent changes in synaptic strength are essential to most forms of learning. It is becoming increasingly clear that synaptic dysfunction is central to the etiology and progression of a wide range of neuropsychiatric and neurodevelopmental disorders. The main goal of my research program is to understand the cellular and molecular basis of activity-dependent changes in synaptic strength at both excitatory and inhibitory connections, and how such changes are modified during pathological conditions. In our studies we use brain slice electrophysiology and pharmacology, two-photon laser microscopy, optogenetics and a wide-range of molecular manipulations. To gain insights into the mechanisms of synaptic function, we include in our studies functional analyses of transgenic mice for several synaptic proteins, as well as mouse models for various neuropsychiatric conditions, including Alzheimer’s disease, autistic spectrum disorders and schizophrenia.

Selected Publications

 

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.

Monday HR and Castillo PE (2017) Closing the gap: long-term presynaptic plasticity in brain function and disease. Curr Opin Neurobiol 45:106-112.

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.

Klein ME, Castillo PE, Jordan BA (2015) Coordination between translation and degradation regulates inducibility of mGluR-LTD. Cell Reports 10:1459–66.

Younts TJ, Castillo PE (2014) Endogenous cannabinoid signaling at inhibitory interneurons. Curr Opin Neurobiol. 26:42-50.

Klein ME, Younts TJ, Castillo, PE, Jordan, BA (2013) RNA-binding protein Sam68 controls synapse number and local β-actin mRNA metabolism in dendrites. Proc Nat Acad Sci USA. 110(8):3125-3130.

Kaeser-Woo YJ, Younts TJ, Yang X, Zhou P, Wu D, Castillo PE, Südhof TC (2013) Synaptotagmin-12 phosphorylation by cAMP-dependent protein kinase is essential for hippocampal mossy fiber LTP. J. Neurosci. 33(23):9769-9780.

Younts TJ, Chevaleyre V, Castillo PE (2013) CA1 pyramidal cell theta-burst firing triggers endocannabinoid-mediated long-termdepression at both somatic and dendritic inhibitory synapses. J. Neurosci. 33:13743-13757.

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.

Chiu CQ, Puente N, Grandes P, Castillo PE (2010) Dopaminergicmodulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex. J Neurosci. 30, 7236–48.

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 synapsesNeuron. 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 longterm 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.

More Information About Dr. Pablo Castillo

Dominick P. Purpura Department of Neuroscience

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

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

Tel: 718.430.3263
pablo.castillo@einstein.yu.edu

Research Information