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

CAITLIN K. MONAGHAN, G. WILLIAM CHAPMAN IV, MICHAEL E. HASSELMO

Abstract:

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