Neural dynamics underlying associative learning in the dorsal and ventral hippocampus.

Animals associate cues with outcomes and update these associations as new information is presented. This requires the hippocampus, yet how hippocampal neurons track changes in cue-outcome associations remains unclear. Using two-photon calcium imaging, we tracked the same dCA1 and vCA1 neurons across days to determine how responses evolve across phases of odor-outcome learning. Initially, odors elicited robust responses in dCA1, whereas, in vCA1, odor responses primarily emerged after learning and embedded information about the paired outcome. Population activity in both regions rapidly reorganized with learning and then stabilized, storing learned odor representations for days, even after extinction or pairing with a different outcome. Additionally, we found stable, robust signals across CA1 when mice anticipated outcomes under behavioral control but not when mice anticipated an inescapable aversive outcome. These results show how the hippocampus encodes, stores and updates learned associations and illuminates the unique contributions of dorsal and ventral hippocampus.

Vasoactive Intestinal Polypeptide-Expressing Interneurons in the Hippocampus Support Goal-Oriented Spatial Learning.

Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP+), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP+ INs and computational modeling further showed that VIP+ disinhibition is necessary for goal-directed learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning. VIDEO ABSTRACT.

Open Ephys electroencephalography (Open Ephys + EEG): a modular, low-cost, open-source solution to human neural recording.

OBJECTIVE: Electroencephalography (EEG) offers a unique opportunity to study human neural activity non-invasively with millisecond resolution using minimal equipment in or outside of a lab setting. EEG can be combined with a number of techniques for closed-loop experiments, where external devices are driven by specific neural signals. However, reliable, commercially available EEG systems are expensive, often making them impractical for individual use and research development. Moreover, by design, a majority of these systems cannot be easily altered to the specification needed by the end user. We focused on mitigating these issues by implementing open-source tools to develop a new EEG platform to drive down research costs and promote collaboration and innovation. APPROACH: Here, we present methods to expand the open-source electrophysiology system, Open Ephys (www.openephys.org), to include human EEG recordings. We describe the equipment and protocol necessary to interface various EEG caps with the Open Ephys acquisition board, and detail methods for processing data. We present applications of Open Ephys + EEG as a research tool and discuss how this innovative EEG technology lays a framework for improved closed-loop paradigms and novel brain-computer interface experiments. MAIN RESULTS: The Open Ephys + EEG system can record reliable human EEG data, as well as human EMG data. A side-by-side comparison of eyes closed 8-14 Hz activity between the Open Ephys + EEG system and the Brainvision ActiCHamp EEG system showed similar average power and signal to noise. SIGNIFICANCE: Open Ephys + EEG enables users to acquire high-quality human EEG data comparable to that of commercially available systems, while maintaining the price point and extensibility inherent to open-source systems.

In Vivo Imaging of Dentate Gyrus Mossy Cells in Behaving Mice.

Mossy cells in the hilus of the dentate gyrus constitute a major excitatory principal cell type in the mammalian hippocampus; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon Ca2+ imaging to monitor the activity of mossy cells in awake, behaving mice. We find that mossy cells are significantly more active than dentate granule cells in vivo, exhibit spatial tuning during head-fixed spatial navigation, and undergo robust remapping of their spatial representations in response to contextual manipulation. Our results provide a functional characterization of mossy cells in the behaving animal and demonstrate their active participation in spatial coding and contextual representation.

Sublayer-Specific Coding Dynamics during Spatial Navigation and Learning in Hippocampal Area CA1.

The mammalian hippocampus is critical for spatial information processing and episodic memory. Its primary output cells, CA1 pyramidal cells (CA1 PCs), vary in genetics, morphology, connectivity, and electrophysiological properties. It is therefore possible that distinct CA1 PC subpopulations encode different features of the environment and differentially contribute to learning. To test this hypothesis, we optically monitored activity in deep and superficial CA1 PCs segregated along the radial axis of the mouse hippocampus and assessed the relationship between sublayer dynamics and learning. Superficial place maps were more stable than deep during head-fixed exploration. Deep maps, however, were preferentially stabilized during goal-oriented learning, and representation of the reward zone by deep cells predicted task performance. These findings demonstrate that superficial CA1 PCs provide a more stable map of an environment, while their counterparts in the deep sublayer provide a more flexible representation that is shaped by learning about salient features in the environment. VIDEO ABSTRACT.