Optogenetic frequency scrambling of hippocampal theta oscillations dissociates working memory retrieval from hippocampal spatiotemporal codes

Abstract

The precise temporal coordination of activity in the brain is thought to be fundamental for memory function. Inhibitory neurons in the medial septum provide a prominent source of innervation to the hippocampus and play a major role in controlling hippocampal theta (~8 Hz) oscillations. While pharmacological inhibition of medial septal neurons is known to disrupt memory, the exact role of septal inhibitory neurons in regulating hippocampal representations and memory is not fully understood. Here, we dissociate the role of theta rhythms in spatiotemporal coding and memory using an all-optical interrogation and recording approach. We find that optogenetic frequency scrambling stimulations abolish theta oscillations and modulate a portion of neurons in the hippocampus. Such stimulation decreased episodic and working memory retrieval while leaving hippocampal spatiotemporal codes intact. Our study suggests that theta rhythms play an essential role in memory but may not be necessary for hippocampal spatiotemporal codes.

A population code for idiothetic representations in the hippocampal-septal circuit

“…In a previous study, we assessed spatiotemporal tuning in a linear maze where sequential tones were presented in order to extend the length of behavioral sequences leading to reward consumption [34] (3 d ). Here, we find that adding a tone sequence to the linear track task changes significantly the spatiotemporal representations of CA1 neurons (2-ANOVA, F 4 = 265.6141, p < 0.0001 for the interaction between modality and presence of tones).…”

“…Similarly, time cells tuning properties could be defined with respect to internal variables, including network activity [31]. Importantly, CA1 pyramidal neurons idiothetic representations are not limited to time, but also include distance [32][33][34] (see McNaughton et al [25] and Mehta [35] for review) and speed [36]. These studies suggest that rather than representing current events, the hippocampus may encode experiences into a series of temporally organized activities.…”

“…In particular, so-called 'time cells' have been defined experimentally by clamping locomotor speed and distance traveled using running treadmills [6,30]. Importantly, CA1 pyramidal neurons idiothetic representations are not limited to time, but also include distance [6,[31][32][33] (see McNaughton et al [25] and Mehta [34] for review) and speed [35,36]. Beyond space and time, the properties of hippocampal neurons have also been defined with respect to internal variables, including network activity [37].…”

“…In particular, so-called ‘time cells’ have been defined experimentally by clamping locomotor speed and distance traveled using running treadmills [6, 30]. Importantly, CA1 pyramidal neurons idiothetic representations are not limited to time, but also include distance [6, 31–33] (see McNaughton et al . [25] and Mehta [34] for review) and speed [35, 36].…”

“…Similarly, time cells tuning properties could be defined with respect to internal variables, including network activity [31]. Importantly, CA1 pyramidal neurons idiothetic representations are not limited to time, but also include distance [32–34] (see McNaughton et al . [25] and Mehta [35] for review) and speed [36].…”