RT Journal Article SR Electronic T1 Synaptic Drive onto Inhibitory and Excitatory Principal Neurons of the Mouse Lateral Superior Olive JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0106-25.2025 DO 10.1523/ENEURO.0106-25.2025 VO 12 IS 5 A1 Haragopal, Hariprakash A1 Voytek, Mara J. A1 Winters, Bradley D. YR 2025 UL http://www.eneuro.org/content/12/5/ENEURO.0106-25.2025.abstract AB Principal neurons (PNs) of the lateral superior olive (LSO) are a critical component of brain circuits that compare information between the two ears to extract sound source-location-related cues. LSO PNs are not a homogenous group but differ in their transmitter type, intrinsic membrane properties, and projection pattern to higher processing centers in the inferior colliculus. Glycinergic inhibitory LSO PNs have higher input resistance than glutamatergic excitatory LSO PNs (∼double). This suggests that the inhibitory cell type has a lower minimum input or signal intensity required to produce an output (activation threshold) which may impact how they integrate binaural inputs. However, cell-type-specific differences in the strength of synaptic drive could offset or accentuate such differences in intrinsic excitability and have not been assessed. To evaluate this possibility, we used a knock-in mouse model to examine spontaneous and electrically stimulated (evoked) synaptic events in LSO PN types using voltage-clamp technique. Both excitatory and inhibitory spontaneous postsynaptic currents were larger in inhibitory LSO PNs, but evoked events were not. Additionally, we found that LSO PN types had inputs with similar short-term plasticity and number of independent fibers. An important contrast was that inhibitory LSO PNs received inhibitory inputs with slower decay kinetics which could impact integrative functions. These data suggest that synaptic inputs onto LSO PNs are unlikely to offset excitability differences. Differences in activation threshold along with transmitter type and projection laterality may allow for distinct roles for LSO PN types in inferior colliculus information processing.