TY - JOUR T1 - Excitatory Post Synaptic Potentials Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0050-15.2016 SP - ENEURO.0050-15.2016 AU - Corey D. Acker AU - Erika Hoyos AU - Leslie M. Loew Y1 - 2016/05/02 UR - http://www.eneuro.org/content/early/2016/05/02/ENEURO.0050-15.2016.abstract N2 - Excitatory postsynaptic potentials (EPSPs) occur when the neurotransmitter glutamate binds to postsynaptic receptors located on small pleomorphic membrane protrusions called dendritic spines. To transmit the synaptic signal, these potentials must travel through the spine neck and the dendritic tree to reach the soma. Due to their small size, the electrical behavior of spines and their ability to compartmentalize electrical signals has been very difficult to assess experimentally. In this study, we developed a method to perform simultaneous 2-photon voltage-sensitive dye recording with 2-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in single spines on the basal dendrites of L5 pyramidal neurons in acute brain slices from CD1 control mice. We were able to record uncaging-evoked spine potentials that resembled miniature EPSPs at the soma from a wide range of spine morphologies. In proximal spines, these potentials averaged 13.0mV (range 6.5 – 30.8mV, N = 20) for an average somatic EPSP of 0.59mV, while the mean attenuation ratio (spine/soma) was found to be 25.3. Durations of spine EPSP waveforms were found to be 11.7ms on average. Modeling studies demonstrate the important role that Rneck plays in spine EPSP amplitudes. Simulations used to estimate Rneck by fits to voltage-sensitive dye measurements produced a mean of 179MΩ (range 23 – 420MΩ, N = 19). Independent measurements based on FRAP of a cytosolic dye from spines of the same population of neurons produced a mean Rneck estimate of 204MΩ (range 52 – 521MΩ, N = 34).Significance Statement: While an excitatory synaptic input may typically generate a ∼0.5mV depolarization at the soma, the magnitude of depolarization at its point of origin, the dendritic spine, is a subject of debate. We developed optical methods to excite and measure excitatory potentials at the target spine on the dendrites of cortical pyramidal neurons. These potentials are typically smaller than some previous reports, but are still over 20 times larger on average in basal dendrite spines than at the soma. We also show evidence that the spine neck resistance is an important biophysical parameter controlling these elementary neuronal input signals. The results provide a requisite basis for further studies on how synaptic inputs drive local voltage-dependent processes and cellular responses. ER -