Alteration of theta timescale dynamics of hippocampal place cells by a cannabinoid is associated with memory impairment.

The integrity of the hippocampus is critical for both spatial navigation and episodic memory, but how its neuronal firing patterns underlie those functions is not well understood. In particular, the modality by which hippocampal place cells contribute to spatial memory is debated. We found that administration of the cannabinoid receptor agonist CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol) induced a profound and reversible behavioral deficit in the hippocampus-dependent delayed spatial alternation task. On the one hand, despite severe memory impairment, the location-dependent firing of CA1 hippocampal place cells remained mostly intact. On the other hand, both spike-timing coordination between place cells at the theta timescale and theta phase precession of spikes were reversibly reduced. These results raise the possibility that cannabinoids impair memory primarily by altering short-term temporal dynamics of hippocampal neurons. We hypothesize that precise temporal coordination of hippocampal neurons is necessary for guiding behavior in spatial memory tasks.