Synaptic transmission underlies every aspect of nervous system function. How we think, feel, act and learn, all rely on information transfer between nerve cells, and 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 molecular basis of activity-dependent changes in synaptic strength at both excitatory and inhibitory connections, and how such changes are modified during pathological conditions. While most of our studies use the hippocampal formation, a brain area critically involved in memory formation, we have also analyzed synaptic function and plasticity in the amygdala, cerebellum and prefrontal cortex. In our studies we use a combination of electrophysiological, pharmacological and molecular biological techniques. To gain insights into the mechanisms of synaptic plasticity, we also 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.
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. Nature Neurosci 14:866-73.
Castillo PE, Chiu CQ, Carroll RC (2011) Long-term plasticity at inhibitory synapses. Current Opinion in Neurobiology 21:328-338.
Chávez AE, Chiu CQ, Castillo PE (2010) TRPV1 activation by endogenous anandamide triggers postsynaptic LTD in dentate gyrus. Nature Neurosci 13:1511-8.
Chiu CQ, Puente N, Grandes P, Castillo PE (2010) Dopaminergic modulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex. J Neurosci 30, 7236-48.
Polydoro M, Acker CM, Duff K, Castillo PE & Davies P (2009) Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci 29, 10741-9.
Heifets BD and Castillo PE (2009) Endocannabinoid signaling and long-term synaptic plasticity. Annu. Rev. Physiology. 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 U S A 105, 10250-5.
Chiu CQ & Castillo PE (2008) Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus. Neuropharmacology 54, 68-78.
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 PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu. Rev. Neurosci. 29:37-75.
