Differential inhibitory configurations segregate frequency selectivity in the mouse inferior colliculus

Receptive fields and tuning curves of sensory neurons represent the neural substrate that allow animals to efficiently detect and distinguish external stimuli. They are progressively refined to create diverse sensitivity and selectivity for neurons along ascending central pathways. However, the neural circuitry mechanisms have not been directly determined for such fundamental qualities in relation to sensory neurons9 functional organizations, due to the technical difficulty of correlating neurons9 input and output. Here, we obtained spike outputs and synaptic inputs from the same neurons within characteristically defined neural ensembles, to determine the synaptic mechanisms driving their diverse frequency selectivity in the mouse inferior colliculus. We find that the synaptic strength and timing of excitatory and inhibitory inputs are configured differently and independently within individual neurons9 receptive fields, which segregate sensitive and selective neurons and endow neural populations with broad receptive fields and sharp frequency tuning. By computationally modeling spike outputs from integrating synaptic inputs and comparing them with real spike responses of the same neurons, we show that space-clamping errors did not qualitatively affect the estimation of spike responses derived from synaptic currents in in vivo voltage-clamp recordings. These data suggest that heterogeneous inhibitory circuits co-exist locally for a parallel but differentiated representation of incoming signals. SIGNIFICANCE STATEMENT Sensitivity and selectivity are functional qualities of sensory systems to facilitate animal9s survival. There is little direct evidence for the synaptic basis of neurons9 functional variance within neural ensembles. Here we adopted a novel framework to fill such a long-standing gap by uniting population activities with single cells9 spike outputs and their synaptic inputs. Furthermore, the effects of space-clamping errors on subcortical synaptic currents were evaluated in vivo , by comparing recorded spike responses and simulated spike outputs from computationally integrating synaptic inputs. Our study illustrated that the synaptic strength and timing of inhibition relative to excitation can be configured differently for neurons within a defined neural ensemble, to segregate their selectivity. It provides new insights into co-existing heterogeneous local circuits.