Hippocampal cells are central to spatial and predictive representations, and experience replays by place cells are crucial for learning and memory. Nonetheless, how hippocampal replay patterns dynamically change during the learning process remains to be elucidated. Here, we designed a spatial task in which rats learned a new behavioral trajectory for reward. We found that as rats updated their behavioral strategies for a novel salient location, hippocampal cell ensembles increased theta-sequences and sharp wave ripple-associated synchronous spikes that preferentially replayed salient locations and reward-related contexts in reverse order. The directionality and contents of the replays progressively varied with learning, including an optimized path that had never been exploited by the animals, suggesting prioritized replays of significant experiences on a predictive map. Online feedback blockade of sharp wave ripples during a learning process inhibited stabilizing optimized behavior. These results implicate learning-associated experience replays that act to learn and reinforce specific behavioral strategies.
Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.
We present a new technique for the simultaneous capture of bioelectrical time signals from the brain and peripheral organs of freely moving rodents. The recording system integrates all systemic signals into an electrical interface board that is mounted on an animal's head for an extended period. The interface board accommodates up to 48 channels, enabling us to analyze neuronal activity patterns in multiple brain regions by comparing a variety of physiological body states over weeks and months. This technique will advance the understanding of the neurophysiological correlate of mind-body associations in health and disease.
The hippocampus contains place cells representing spaces in an environment, and these place cells have been suggested to play a fundamental role in the formation of a cognitive map for spatial processing. However, how alterations in the firing patterns of place cells in response to aversive events encode the locations tied to these aversive events is unknown. Here, we analyzed spiking patterns of place cell ensembles in the dorsal hippocampal CA1 region of rats performing a T-maze alternation task with an aversive air-puff stimulation applied at a specific location on one side of a trajectory. The intensity of the air puff was adjusted so that the rats decreased their running speed before passing the aversive location. The addition of the aversive stimulus induced reorganization of place cell ensembles on both left and right trajectories with and without the aversive stimulus, respectively. Specifically, the animals showed a more abundant spatial representation in the vicinity of the aversive location. Removing the aversive stimulus induced new spatial firing patterns on both of the trajectories that differed from those both before and during application of the aversive stimulus. These results demonstrate that hippocampal spatial maps are flexibly reorganized to represent particular aversive events.
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