Biophysical network modeling of temporal and stereotyped sequence propagation of neural activity in the premotor...

Stereotyped neural sequences are often exhibited in the brain, yet the neurophysiological mechanisms underlying their generation are not fully understood. Birdsong is a prominent model to study such behavior, particularly because juvenile songbirds progressively learn from their tutors and by adulthood are able to sing stereotyped song patterns. The songbird premotor nucleus HVC coordinates motor and auditory activity responsible for learned vocalizations. The HVC comprises three neural populations that have distinct in vitro and in vivo electrophysiological responses. Typically, models that explain HVC's network either rely on intrinsic HVC circuitry to propagate sequential activity, rely on extrinsic feedback to advance the sequence, or rely on both. Here, we developed a physiologically realistic neural network model incorporating the three classes of HVC neurons based on the ion channels and the synaptic currents that had been pharmacologically identified. Our model is based on a feedforward chain of microcircuits that encode for the different sub-syllabic segments (SSSs) and that interact with each other through structured feedback inhibition. The network reproduced the in vivo activity patterns of each class of HVC neurons and unveiled key intrinsic and synaptic mechanisms that govern the sequential propagation of neural activity by highlighting important roles for the T-type Ca²⁺ current, Ca²⁺-dependent K⁺ current, A-type K⁺ current, hyperpolarization-activated inward current, as well as excitatory and inhibitory synaptic currents. The result is a biophysically realistic model that suggests an improved characterization of the HVC network responsible for song production in the songbird.