Systemic administration of two different anxiolytic drugs decreases local field potential theta frequency in the medial entorhinal cortex without affecting grid cell firing fields

- Anxiolytic drugs reduce local field potential theta frequency in the medial entorhinal cortex.
- The intercept, and not the slope, of the linear fit to theta frequency plotted across running speeds is reduced.
- Grid cell periodicity and grid field spacing remain intact after drug administration.
- The only effect on grid cells is theta rhythmic firing slows to keep phase locking to local field potential theta.

Neurons coding spatial location (grid cells) are found in medial entorhinal cortex (MEC) and demonstrate increasing size of firing fields and spacing between fields (grid scale) along the dorsoventral axis. This change in grid scale correlates with differences in theta frequency, a 6-10 Hz rhythm in the local field potential (LFP) and rhythmic firing of cells. A relationship between theta frequency and grid scale can be found when examining grid cells recorded in different locations along the dorsoventral axis of MEC.When describing the relationship between theta frequency and grid scale, it is important to account for the strong positive correlation between theta frequency and running speed. Plotting LFP theta frequency across running speeds dissociates two components of this relationship: slope and intercept of the linear fit. Change in theta frequency through a change in the slope component has been modeled and shown experimentally to affect grid scale, but the prediction that change in the intercept component would not affect grid scale has not been tested experimentally. This prediction about the relationship of intercept to grid scale is the primary hypothesis tested in the experiments presented here.All known anxiolytic drugs decrease hippocampal theta frequency despite their differing mechanisms of action. Specifically, anxiolytics decrease the intercept of the theta frequency-running speed relationship in the hippocampus. Here we demonstrate that anxiolytics decrease the intercept of the theta frequency-running speed relationship in the MEC, similar to hippocampus, and the decrease in frequency through this change in intercept does not affect grid scale.