Targeted Activation of Hippocampal Place Cells Drives Behaviour
Post by Cody Walters
What’s the science?
The hippocampus contains neurons that are preferentially active at specific locations in space. The coordinated activity of these hippocampal ‘place cells’ is thought to form a cognitive map that stores spatial information and is used during memory-guided decision-making. While much research has been done correlating place cell activity with spatial memory, there has been comparatively little research examining the causal relationship between place cell activity and behavior. This week in Cell, Robinson et al. provided direct causal evidence that place cell activation can trigger a learned, location-specific behavior.
How did they do it?
The authors used a virtual reality spatial navigation task in which head-fixed mice navigated a linear track. The authors then used two-photon calcium imaging to measure layer CA1 pyramidal cell calcium fluorescence (a proxy for neuronal firing) and two-photon targeted optogenetics to selectively drive the activity of specific hippocampal neurons. In the virtual reality linear track, mice had to navigate to the reward zone (near the end of the track), remain stationary there for 3 seconds, then lick 3 times in order to receive a sugar-water reward. The virtual environment had an optogenetic stimulation point midway between the start zone and the reward zone. Hippocampal neurons were classified as being either start zone place cells, reward zone place cells, other place cells (corresponding to a position on the track other than the start zone or reward zone), or non-place cells (showing no spatial tuning).
What did they find?
The authors found that reward zone place cell stimulation resulted in an increase in licking behavior at the stimulation point. This result suggests that place cell activation can retrieve a learned behavior associated with the location in space encoded by those place cells. Furthermore, the authors found that the reward zone place cell activation resulted in a progressive deceleration near the stimulation point. On the other hand, start zone place cell activation resulted in reward zone overshoots and more time spent outside the reward zone.
Targeted optogenetic stimulation of place cell populations was found to either enhance or suppress calcium activity in non-targeted hippocampal neurons. The authors then demonstrated that the magnitude of suppression was greatest during the start zone place cell and reward zone place cell stimulation conditions (with no observed difference in the magnitude of suppression during non-place cell stimulation relative to the no stimulation condition). This result suggests that place cells might be involved in recruiting inhibitory interneurons to regulate network excitability. Lastly, the authors showed that optogenetic stimulation shifted place fields toward the stimulation point and caused a reduction in reward zone lick rate.
What’s the impact?
This study demonstrates that place cell stimulation can trigger location-specific behavior and cause place field remapping. This study extends our knowledge of the hippocampal cognitive map and its functional significance by providing direct evidence of a causal link between place cell activation and spatial behavior.
Robinson et al. Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behavior. Cell. (2020). Access the original scientific publication here.