Multiplexing of functionally distinct inputs by intrinsic modulation of spike timing in a monoaminergic nucleus

Monoaminergic nuclei such as the serotonergic dorsal raphe nucleus (DRN) receive functionally distinct streams of synaptic inputs, yet whether and how these are transformed into distinct population codes remains unknown. Combining electrophysiology and computational modeling, we show that DRN 5-HT neurons exhibit separable spiking representations of two major excitatory inputs-those from the lateral habenula (LHb) and the medial prefrontal cortex (mPFC). Dual-color opsin experiments revealed that 5-HT neurons received convergent input from both regions. Subthreshold events were similar between inputs, but suprathreshold spiking showed input-specific latencies and dispersion. We found a low-threshold calcium conductance that selectively boosts slow excitatory inputs and shapes membrane noise to generate input-specific variation of spike latency and jitter. Stochastic simulations confirmed that these cell-intrinsic properties are sufficient to generate distinct output spike patterns. This emergent population spike synchrony code provides a means for the DRN to widely broadcast these streams as a multiplexed signal.