Pablo Castillo

Associate Professor
Synaptic physiology; mechanisms of activity-dependent changes of synaptic efficacy in the mammalian brain.

Kennedy Center
Room 703
(718) 430-3263
pcastill@aecom.yu.edu


 

Changes in synaptic efficacy are essential for neuronal development, learning, and memory formation. In our laboratory we study how synapses modify their efficacy as well as the functional impact of such changes in a neural network. We investigate the properties of excitatory and inhibitory synapses in the mammalian brain and the mechanisms of synaptic plasticity. One of our main goals is to elucidate both the specific molecular events that underlie various forms of synaptic plasticity and the exact modifications in synaptic proteins that are responsible for the observed, short- and long-lasting changes in synaptic efficacy. While most of our knowledge on long-term synaptic plasticity is derived from studies at excitatory synapses, little is known about plasticity at inhibitory synapses. We have recently found that endogenous cannabinoids mediate long-term plasticity at inhibitory synapses in the hippocampus. We are currently investigating the molecular mechanisms as well as the functional relevance of this form of plasticity.

 

Selected Publications

Takahashi K.A. and Castillo P.E. The CB1 receptor mediates glutamatergic synaptic depression in the hippocampus. Neuroscience (in press), 2006.

Chevaleyre V., Takahashi K.A. and Castillo P.E.  Endocannabinoid-mediated Synaptic Plasticity in the CNS. Annu Rev Neurosci 29:37-75, 2006.

Mato S., Chevaleyre V., Robbe D., Pazos A., Castillo P.E. and Manzoni O.J. A single in-vivo exposure to delta-9-Tetrahydrocannabinol blocks endocannabinoid-mediated synaptic plasticity. Nature Neurosci. 7:585-587, 2004.

Chevaleyre V. and Castillo P.E. Heterosynaptic LTD of hippocampal GABAergic synapses: A novel role of endocannabinoids in regulating excitability. Neuron 38:461-472, 2003.

Castillo P.E., Schoch S, Schmitz F, Sudhof T.C. and Malenka R.C. RIM1alpha is required for presynaptic long-term potentiation. Nature 415:327-330, 2002.

Chevaleyre V. and Castillo P.E. Assessing the role of Ih channels in synaptic transmission and mossy fiber LTP. Proc Natl Acad Sci U S A. 99:9538-43, 2002.

Castillo P.E., Janz R., Südhof T.C., Tzounopoulos T., Malenka R.C. and Nicoll R.A. Rab3A is essential for mossy fibre long-term-potentiation in the hippocampus. Nature 388, 590-593, 1997.

Castillo P.E., Malenka R.C. and Nicoll R.A. Kainate receptors mediate a slow postsynaptic current at hippocampal mossy fiber synapses. Nature 388, 182-186, 1997.