Mechanisms of plasticity for pup call sounds in the maternal auditory cortex

Distress calls of mice pups outside their nest elicit reliable pup retrieval in maternal female mice but not in their virgin (`naive') conspecifics. However, when co-housed with maternal mice, naive mice become `experienced' and learn to reliably perform pup retrieval. This process correlates with neuronal changes in the primary auditory cortex (A1): While excitatory (E) neuron responses are sharply tuned to a certain inter- pup-call interval and inhibitory (I) neuron responses are broadly tuned in naive mice, the two neuron types are co-tuned in experienced mice. This change in behavior and tuning is mediated by oxytocin (Marlin et al., 2015; Schiavo et al., 2020). Here, we aim to dissect the underlying mechanisms behind the behaviorally-relevant changes in tuning of excitatory and inhibitory neurons from naive to experienced mice by combining computational modeling and in-vitro experiments. Using optogenetic targeting of somatostatin-positive (SST) or parvalbumin-positive (PV) inhibitory neurons, we quantified short-term plasticity (STP) at SST-to-E and PV-to-E connections. Furthermore, pairing experiments reveal sufficient long-term plasticity at SST-to-E but not PV-to-E connections. Using a model, we study the interaction of three neuron populations (E, SST, and PV) with synapses experiencing experimentally-identified short- and long-term plasticity. We show that 1) short-term plasticity leads to the tuning of excitatory and inhibitory neurons to specific inter-stimulus intervals (ISIs), and 2) oxytocin-gated long-term plasticity of E-to-E and SST-to-E connections leads to experience-dependent changes in the tuning properties from naive to experienced mice. Furthermore, 3) short-term plasticity at SST-to-E and PV-to-E synapses can control the excitatory signal amplitude without changing the tuning properties. Our results reveal that short- and long-term plasticity cooperate to generate tuning of excitatory and inhibitory neurons in local microcircuits and have important implications for maternal behavior.