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1.  Control of submillisecond synaptic timing in binaural coincidence detectors by Kv1 channels 
Nature Neuroscience  2010;13(5):601-609.
Neurons in the medial superior olive (MSO) process sound localization cues through binaural coincidence detection, in which excitatory synaptic inputs from each ear are segregated onto different branches of a bipolar dendritic structure and sum at the soma and axon with submillisecond time resolution. Although synaptic timing and dynamics critically shape this remarkable computation, synaptic interactions with intrinsic ion channels have received less attention. Using paired somatic and dendritic patch-clamp recordings in gerbil brainstem slices together with compartmental modeling, we show that activation of Kv1 channels by dendritic EPSPs accelerates membrane repolarization in a voltage-dependent manner and actively improves the time resolution of synaptic integration. We demonstrate that a somatically biased gradient of Kv1 channels underlies the degree of compensation for passive cable filtering during propagation of EPSPs in dendrites. Thus both the spatial distribution and properties of Kv1 channels play a key role in preserving binaural synaptic timing.
PMCID: PMC3375691  PMID: 20364143
2.  Asymmetric Excitatory Synaptic Dynamics Underlie Interaural Time Difference Processing in the Auditory System 
PLoS Biology  2010;8(6):e1000406.
In order to localize sounds in the environment, the auditory system detects and encodes differences in signals between each ear. The exquisite sensitivity of auditory brain stem neurons to the differences in rise time of the excitation signals from the two ears allows for neuronal encoding of microsecond interaural time differences.
Low-frequency sound localization depends on the neural computation of interaural time differences (ITD) and relies on neurons in the auditory brain stem that integrate synaptic inputs delivered by the ipsi- and contralateral auditory pathways that start at the two ears. The first auditory neurons that respond selectively to ITD are found in the medial superior olivary nucleus (MSO). We identified a new mechanism for ITD coding using a brain slice preparation that preserves the binaural inputs to the MSO. There was an internal latency difference for the two excitatory pathways that would, if left uncompensated, position the ITD response function too far outside the physiological range to be useful for estimating ITD. We demonstrate, and support using a biophysically based computational model, that a bilateral asymmetry in excitatory post-synaptic potential (EPSP) slopes provides a robust compensatory delay mechanism due to differential activation of low threshold potassium conductance on these inputs and permits MSO neurons to encode physiological ITDs. We suggest, more generally, that the dependence of spike probability on rate of depolarization, as in these auditory neurons, provides a mechanism for temporal order discrimination between EPSPs.
Author Summary
Animals can locate the source of a sound by detecting microsecond differences in the arrival time of sound at the two ears. Neurons encoding these interaural time differences (ITDs) receive an excitatory synaptic input from each ear. They can perform a microsecond computation with excitatory synapses that have millisecond time scale because they are extremely sensitive to the input's “rise time,” the time taken to reach the peak of the synaptic input. Current theories assume that the biophysical properties of the two inputs are identical. We challenge this assumption by showing that the rise times of excitatory synaptic potentials driven by the ipsilateral ear are faster than those driven by the contralateral ear. Further, we present a computational model demonstrating that this disparity in rise times, together with the neurons' sensitivity to excitation's rise time, can endow ITD-encoding with microsecond resolution in the biologically relevant range. Our analysis also resolves a timing mismatch. The difference between contralateral and ipsilateral latencies is substantially larger than the relevant ITD range. We show how the rise time disparity compensates for this mismatch. Generalizing, we suggest that phasic-firing neurons—those that respond to rapidly, but not to slowly, changing stimuli—are selective to the temporal ordering of brief inputs. In a coincidence-detection computation the neuron will respond more robustly when a faster input leads a slower one, even if the inputs are brief and have similar amplitudes.
PMCID: PMC2893945  PMID: 20613857

Results 1-2 (2)