Place cell firing cannot support navigation without intact septal circuits

Abstract

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location‐specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: Tetracaine, a local anesthetic; muscimol, a GABA‐A agonist; and gabazine, a GABA‐A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat's ability to navigate to a hidden goal. After gabazine, location‐specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location‐specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.

Cooling of medial septum reveals theta phase lag coordination of hippocampal cell assemblies

“…MS cooling exerted a robust effect on spatial memory, comparable to damage or pharmacologic inactivation of MS 60,61 . Unlike neuron-specific manipulations 8,11,12,62 , local cooling affects all neurons in MS and possibly its surrounding structures.…”

Speed modulation of hippocampal theta frequency and amplitude predicts water maze learning

“…Given the theoretical (Burgess & O'Keefe, 2011) and empirical (Bolding, Ferbinteanu, Fox, & Muller, 2019;Brandon et al, 2011;Koenig, Linder, Leutgeb, & Leutgeb, 2011) support for hippocampal theta to contribute to spatial representation and spatial learning (McNaughton et al, 2006), we sought to carry out a more in-depth analysis on how hippocampal theta oscillations are related to locomotion/swimming parameters (i.e., speed and acceleration) in the water maze, and how the relationship may be linked to learning. We show that hippocampal theta frequency and signal envelope (amplitude/power) are positively scaled with speed but less so with acceleration.…”

Speed modulation of hippocampal theta frequency and power predicts water maze learning

“…Some experimental evidence suggests self-motion- and sensory-derived (mostly visual) signals may underlie the existence of multiple speed information in the spatial circuit (Campbell et al, 2018; Jayakumar et al, 2019). The nature of the speed information that the CA1 theta LFP carries is unclear; however, this theta appears to be essential for spatial representation in the HPC and medial entorhinal cortex (Brandon et al, 2011; Koenig et al, 2011; Bolding et al, 2019), and uncoupling of self-motion and actual movement appear to suppress its relationship with speed (Czurko et al, 1999; Shin and Talnov, 2001; Terrazas et al, 2005; Kuo et al, 2011; Ravassard et al, 2013). Of interest, there is no reported change in place cell firing rates in the water maze in relation to speed (Hollup et al, 2001a, b).…”

“…Given the theoretical (Burgess and O’Keefe, 2011) and empirical (Brandon et al, 2011; Koenig et al, 2011; Bolding et al, 2019) support for hippocampal theta to contribute to spatial representation and spatial learning (McNaughton et al, 2006), we sought to carry out a more in-depth analysis on how hippocampal theta oscillations are related to locomotion/swimming parameters (i.e. speed and acceleration) in the water maze, and how the relationship may be linked to learning.…”