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Synaptic clustering increases the dynamic range of neuronal computation.
Rei Yamada (Hiroshi Kuba)

Synaptic clustering in principle promotes supralinear integration and increases the impact of spatiotemporally correlated inputs. However, we show in avian binaural coincidence detectors that clustering of synapses rather promotes the dendritic attenuation but increases the dynamic range of binaural computations.
Auditory coincidence detection is the neuronal basis of encoding interaural time differences (ITDs) for sound source localization and occurs in neurons of nucleus laminaris (NL) of birds. NL neurons change their dendritic morphology according to the tuning-frequency (characteristic frequency: CF), such that those respond to lower frequencies have longer dendrites. However, the functional significance of such morphological arrangement was not clearly understood.
In this study, we analyzed the synaptic distribution along the NL dendrites by local uncaging stimulation using a two-photon laser microscope. We found that synaptic inputs were concentrated distally in the long dendrites of low-CF neurons. We also found that voltage responses at soma were strongly attenuated for those generated at distal dendrites particularly at the strong stimulation. Model study revealed that the clustered inputs at distal dendrite generated large depolarization at the site, which decreased charge influx through glutamate receptors and increased charge efflux through K+ channels, then increased the extent of attenuation in an intensity-dependent manner. This sublinear integration prevented unilateral firing and increased the dynamic range of ITD coding. We concluded that the synaptic clustering at distal dendrite would be a cellular basis to accomplish the sound localization for wide intensity ranges of low frequency sound.
This finding gives a clue to the variations in synapse geometry and dendritic morphology among cell types and/or brain regions, and facilitates our understanding on computation in the brain.

Yamada R, Kuba H. Dendritic synapse geometry optimizes binaural computation in a sound localization circuit. Science Advances 7(48): eabh0024, 2021.


<Figure Legends>
Excitatory synapses are concentrated at distal thin branches in low-CF neurons (top). We performed two-photon glutamate uncaging (1-ms duration) at eight points along short stretch of dendrites (< 15 µm) in a low-CF neurons. The response by quasi-simultaneous stimuli to the points (0.3-ms interpulse interval) (red) was compared with the arithmetic sum of individual responses at the same interval (black). Note that the recorded response was smaller than that the arithmetic sum, indicating that the sublinear integration occurred at the distal dendrites.


Department of Cell Physiology, Graduate School of Medicine, Nagoya University, Japan