Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons

Abstract

SUMMARY Recent studies have shown that hippocampal “time cells” code for sequential moments in temporally organized experiences. However, it is currently unknown whether these temporal firing patterns critically rely on upstream cortical input. Here we employ an optogenetic approach to explore the effect of large-scale inactivation of the medial entorhinal cortex on temporal as well as spatial and object coding by hippocampal CA1 neurons. Medial entorhinal inactivation produced a specific deficit in temporal coding in CA1, and resulted in significant impairment in memory across a temporal delay. In striking contrast, spatial and object coding remained intact. Further, we extended the scope of hippocampal phase precession to include object information relevant to memory and behavior. Overall, our work demonstrates that medial entorhinal activity plays an especially important role for CA1 in temporal coding and memory across time.

On the Integration of Space, Time, and Memory

“…The grid cells of medial entorhinal cortex that constitute a mapping of spatial context also signal elapsed time in rats during treadmill running (Kraus et al, 2015). Conversely, optogenetic inactivation of the medial entorhinal cortex disrupts time cell firing sequences in the hippocampus (Robinson et al, 2017). …”

“…The resulting combination of direct and indirect associations form the structure of a “memory space” organized by continuous dimensions of experience to support the representation of relations among elements of memories and among memories (i.e., relational representation) and flexibility of expression of declarative memories (Howard et al, 2005; Deuker et al, 2016; Eichenbaum, 2017). …”

“…In addition, memory for specific experiences (episodic memory) is characterized by an organization of events in time (Tulving, 1972), and several recent findings have revealed temporally organized hippocampal neuronal activity patterns that support memory (Dragoi & Buzsaki, 2006; Pastalkova et al, 2008; MacDonald et al, 2011; Wikenheiser & Redish, 2015; Cai et al, 2016; reviewed in Eichenbaum, 2014). Combining these lines of evidence, one possible accounting of hippocampal function is the organization of memories in space and time (Eichenbaum, 2017). A key question in pursuing this hypothesis is how neuronal networks within the hippocampus accomplish the combination of spatial and temporal organization.…”

Time (and space) in the hippocampus

“…Many grid cells exhibited multiple firing fields during treadmill running, parallel to the periodic firing fields observed in open fields, suggesting a common mode of information processing for space and time. In addition, recent work has shown that temporary inactivation of the medial entorhinal cortex corrupts time cell sequences in the hippocampus [43]. These combined observations indicate that the medial entorhinal cortex provides an essential cortical input to the hippocampus for the represention of temporally organized experiences.…”

Time regained: how the human brain constructs memory for time

“…Human functional magnetic resonance imaging (fMRI) studies have begun to uncover the neural manifestations of temporal memory [4,5], in parallel with a rich literature involving electrophysiology [6,7] and non-human animals [5,8,9]. Much of this work has implicated the hippocampus, a region known to contribute to episodic memory, in memory for temporal information [4,5,10].…”