Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons

Abstract

The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population, without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information.

Representation of memories in the cortical–hippocampal system: Results from the application of population similarity analyses

“…Furthermore, the consistent failure to observe long term place field deficits following MEC lesions or inactivations (Brandon et al, 2014; Van Cauter et al, 2008; Hales et al, 2014; Miller and Best, 1980; Navawongse and Eichenbaum, 2013; Rueckemann et al, 2015; Schmidt et al, 2013) is also contrary to predictions that grid cells are required to form place cells (Moser et al, 2008). It is possible that the multidimensional approach laid out here may reveal the essential contribution of MEC input to hippocampal function, perhaps in the coding of context.…”

“…The two regions show an impressively similar coding hierarchy for which information drives ensemble similarity, yet MEC lesions do not disrupt the ability of the hippocampus to encode places (Brandon et al, 2014; Van Cauter et al, 2008; Hales et al, 2014; Miller and Best, 1980; Navawongse and Eichenbaum, 2013) or objects that occur in those places (Navawongse and Eichenbaum, 2013). Changes in MEC activity, either endogenous (Fyhn et al, 2007) or experimental (Hales et al, 2014; Navawongse and Eichenbaum, 2013; Rueckemann et al, 2015), reliably cause reconfigurations of the hippocampal firing properties (remapping) with preserved information coded by a different set of cells. This reconfiguration suggests that the MEC provides a broader contextual signal (Eichenbaum and Lipton, 2008) that defines the space of representations with which to encode the specifics of a new memory.…”

Grid scale drives the scale and long-term stability of place maps

“…MEC input likely plays a role in the maintenance of the place map, as inactivation of MEC induces a near instantaneous change in the configuration of place fields, a phenomenon referred to as remapping 9, 10, 34 . However, which features of entorhinal coding drive place stability versus remapping, as well as what impact place cell stability might have on memory, remain unresolved.…”

“…However, while grid cells project to the hippocampus 8 , the examination of place cells in the absence of grid cells has produced mixed results. Temporally-restricted MEC inactivation induced place cell re-mapping 9, 10 and larger interventions, such as MEC lesions, resulted in place field expansion 11, 12 . However, these manipulations eliminated, in addition to grid cells, other functionally-defined MEC neurons, such as border cells that encode environmental boundaries and head direction cells that fire when an animal faces a particular direction 13, 14 .…”

Heterogeneity in hippocampal place coding

“…Confirming that MEC plays a key role in shaping place cell responses, both transient optogenetic inactivation and chemogenetic depolarization of MEC evoke place cell remapping [41 • ,42]. However, causally linking remapping to changes in the activity of specific MEC cell-types remains a formidable goal as, presently, there are no genetic markers by which to distinguish these functional cell-types.…”