The role of parvalbumin positive interneuron activity and plasticity in the prefrontal cortex for movement control

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Movement preparation and inhibition is a crucial skill-set for successfully interacting with the environment. As the executive hub, the medial prefrontal cortex (mPFC) plays a major role in learning, memorizing and executing this skill. Structural and synaptic plasticity in pyramidal cells have been shown to be a key component of learning, executing and recall of learned skills in the mPFC (Frankland et al., 2004; Restivo et al., 2009; Euston et al., 2012). However, how GABAergic inhibitory interneurons (INs) may contribute to the fine-tuning of movement preparation in the mPFC and how inhibitory signaling is changed during skill learning remains far of being understood. Here we hypothesize that changes in the efficacy of excitatory glutamatergic inputs targeting INs, similar to observations in the primary motor cortex (M1, TP6) and the hippocampus (TP1, TP7) may play a role in controlling movement preparation. We further propose that among the various IN types, parvalbumin (PV)-expressing, fast-spiking, perisomatic-inhibitory INs (PVIs) are particularly relevant in this skill (Kvitsiani et al., 2013, Pinto & Dan, 2015, Lagler et al., 2016). Previously, we have established a behavioural movement protocol combined with in vivo optogenetics and electrophysiology to investigate the neuronal underpinnings of movement control in rodents and found that specific subsections of the PFC differentially contribute to this behaviour (Hardung et al., 2017a; Hardung et al., 2017b). Here, we will focus on the role of PVIs in learning and executing the behavioural task. We aim (1) to define discharge activity of mPFC-PVIs during motor control and learning and (2) to identify the impact of mPFC-PVI neuronal activity on movement initiation and inhibition using a combination of in vivo optogenetics and electrophysiology. This will be paralleled by comparative experiments in M1 and the hippocampus by our partners (TP6 Poulet, TP7 Csicsvari). (3) We will further determine the effect of PVI activity on local neural network oscillations and – in collaboration with TP6 (Poulet) – on the putative communication with downstream motor cortex activity. (4) Finally, by applying ex vivo investigations in collaboration with Bartos (TP1), we will measure amplitudes of spontaneous and evoked excitatory signals in PVIs to examine whether PVIs inputs underwent plastic changes. Data will be compared between trained and untrained mice. With these four parallel approaches, the proposed project will provide detailed information on the impact of PVI-specific synaptic plasticity and PVI activity on cognitive movement control and learning and thereby bridge the gap between synaptic plasticity, neuronal activity, and behaviour.