No abstract

The hippocampus is crucial for forming associations between environmental stimuli. However, it is unclear how neural activities of hippocampal neurons dynamically change during the learning process. To address this question, we developed an associative memory task for rats with auditory stimuli. In this task, the rats were required to associate tone pitches (high and low) and ports (right and left) to obtain a reward. We recorded the firing activity of neurons in rats hippocampal CA1 during the learning process of the task. As a result, many hippocampal CA1 neurons increased their firing rates when the rats received a reward after choosing either the left or right port. We referred to these cells as “reward-direction cells.” Furthermore, the proportion of the reward-direction cells increased in the middle-stage of learning but decreased after the completion of learning. This result suggests that the activity of reward-direction cells might serve as “positive feedback” signal that facilitates the formation of associations between tone pitches and port choice.

In this review article we focus on research methodologies for detecting the actual activity of cell assemblies, which are populations of functionally connected neurons that encode information in the brain. We introduce and discuss traditional and novel experimental methods and those currently in development and briefly discuss their advantages and disadvantages for the detection of cell-assembly activity. First, we introduce the electrophysiological method, i.e., multineuronal recording, and review former and recent examples of studies showing models of dynamic coding by cell assemblies in behaving rodents and monkeys. We also discuss how the firing correlation of two neurons reflects the firing synchrony among the numerous surrounding neurons that constitute cell assemblies. Second, we review the recent outstanding studies that used the novel method of optogenetics to show causal relationships between cell-assembly activity and behavioral change. Third, we review the most recently developed method of live-cell imaging, which facilitates the simultaneous observation of firings of a large number of neurons in behaving rodents. Currently, all these available methods have both advantages and disadvantages, and no single measurement method can directly and precisely detect the actual activity of cell assemblies. The best strategy is to combine the available methods and utilize each of their advantages with the technique of operant conditioning of multiple-task behaviors in animals and, if necessary, with brain–machine interface technology to verify the accuracy of neural information detected as cell-assembly activity.

The dissociation between a subjective-criterion performance and forced performance in a sensory detection can provide critical insights into the neural correlates of sensory awareness. Here, we established a behavioral task for rats to test their spatial-visual cue detection ability, using a two alternative choice task with and without a third choice option where animals get rewards only in the objective absence of a visual cue. In the trials without the third option, spatial choice accuracy decreased from near perfect to near chance levels as the visual cue brightness decreased. In contrast, with the third option, the rats exhibited >90% spatial choice accuracy regardless of the cue brightness. The rats chose the third choice option less frequently when the cue was brighter, suggesting that rats have a generalized strategy to make spatial choices only when their internal detection criterion is met. Interestingly, even when the animals chose the third option, they could still significantly and correctly choose the direction of the visual stimuli if they were forced. Our data suggest that the rats’ variable detection performance with identical set of stimuli is derived from stochastic processing of visual signals with a certain internal detection threshold rather than general motivational threshold.