The ability to plan and execute appropriately timed responses to external stimuli is based on a well-orchestrated balance between movement initiation and inhibition. In impulse control disorders involving the prefrontal cortex (PFC) [1], this balance is disturbed, emphasizing the critical role that PFC plays in appropriately timing actions [2-4]. Here, we employed optogenetic and electrophysiological techniques to systematically analyze the functional role of five key subareas of the rat medial PFC (mPFC) and orbitofrontal cortex (OFC) in action control [5-9]. Inactivation of mPFC subareas induced drastic changes in performance, namely an increase (prelimbic cortex, PL) or decrease (infralimbic cortex, IL) of premature responses. Additionally, electrophysiology revealed a significant decrease in neuronal activity of a PL subpopulation prior to premature responses. In contrast, inhibition of OFC subareas (mainly the ventral OFC, i.e., VO) significantly impaired the ability to respond rapidly after external cues. Consistent with these findings, mPFC activity during response preparation predicted trial outcomes and reaction times significantly better than OFC activity. These data support the concept of opposing roles of IL and PL in directing proactive behavior and argue for an involvement of OFC in predominantly reactive movement control. By attributing defined roles to rodent PFC sections, this study contributes to a deeper understanding of the functional heterogeneity of this brain area and thus may guide medically relevant studies of PFC-associated impulse control disorders in this animal model for neural disorders [10-12].

We present a 3D assay for the quantification of the autophagic flux in live cell spheroids by using the fluorescent reporter mRFP-GFP-LC3. The protocol describes the formation of the spheroids from the astrocytoma cell line U343, live long-term 3D fluorescence imaging of drug-treated spheroids, and the image processing workflow required to extract quantitative data on the autophagic flux.

Current neural decoding methods typically aim at explaining behavior based on neural activity via supervised learning. However, since generally there is a strong connection between learning of subjects and their expectations on long-term rewards, we propose NeuRL, an inverse reinforcement learning approach that (1) extracts an intrinsic reward function from collected trajectories of a subject in closed form, (2) maps neural signals to this intrinsic reward to account for long-term dependencies in the behavior and (3) predicts the simulated behavior for unseen neural signals by extracting Q-values and the corresponding Boltzmann policy based on the intrinsic reward values for these unseen neural signals. We show that NeuRL leads to better generalization and improved decoding performance compared to supervised approaches. We study the behavior of rats in a responsepreparation task and evaluate the performance of NeuRL within simulated inhibition and per-trial behavior prediction. By assigning clear functional roles to defined neuronal populations our approach offers a new interpretation tool for complex neuronal data with testable predictions. In per-trial behavior prediction, our approach furthermore improves accuracy by up to 15% compared to traditional methods.

Simultaneous recordings and manipulations of neural circuits that control the behavior of animals is one of the key techniques in modern neuroscience. Rapid advances in optogenetics have led to a variety of probes combining multichannel readout and optogenetic write in. Given the complexity of the brain, it comes as no surprise that the choice of the device is constrained by several factors such as the animal model, the structure and location of the brain area of interest, as well as the behavioral read out. Here we provide an overview of available devices for chronic simultaneous neural recordings and optogenetic manipulation in awake behaving rats. We focus on two fixed arrays and two moveable drives. For both options, we present data from one custom-made (in house) and one commercially available device. Here we provide evidence that simultaneous neural recordings and optogenetic manipulations are feasible with all four tested devices. Further we give detailed information about the recording quality, and also contrast the different features of the probes. As we provide detailed information about equipment and building procedures for combined chronic multichannel readout and optogenetic control with maximum performance at minimized costs, this overview might help especially researchers who want to enter the field of in vivo optophysiology.

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