Impaired Recall of Positional Memory following Chemogenetic Disruption of Place Field Stability

Abstract

SUMMARYThe neural network of the temporal lobe is thought to provide a cognitive map of our surroundings. Functional analysis of this network has been hampered by coarse tools that often result in collateral damage to other circuits. We developed a chemogenetic system to temporally control electrical input into the hippocampus. When entorhinal input to the perforant path was acutely silenced, hippocampal firing patterns became destabilized and underwent extensive remapping. We also found that spatial memory acquired prior to neural silencing was impaired by loss of input through the perforant path. Together, our experiments show that manipulation of entorhinal activity destabilizes spatial coding and disrupts spatial memory. Moreover, we introduce a chemogenetic model for non-invasive neuronal silencing that offers multiple advantages over existing strategies in this setting.

Conditional Knockout of Cav2.1 Disrupts the Accuracy of Spatial Recognition of CA1 Place Cells and Spatial/Contextual Recognition Behavior

“…While moderate impairment was shown during the acquisition of a water maze task, the performance in a contextual fear conditioning task was intact during the acquisition. In addition, deletion of Cav2.1 in the entorhinal cortex, which is a major afferent to the hippocampus, did not directly influence the firing activity of CA1 neurons unlike in other studies reporting that malfunction of the entorhinal cortex caused reductions in either firing rate or spatial information score of CA1 place cells (Brun et al, 2008; Van Cauter et al, 2008; Zhao et al, 2016). This suggests that the effect of moderate deletion of Cav2.1 in the entorhinal cortex was minimal on the place cell activity.…”

Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons

“…Prior experiments have demonstrated cumulative or instantaneous “remapping” of hippocampal place fields during MEC inactivation, though perturbations generally exerted only modest effects on the quality of spatial tuning (Hales et al 2014, Miao et al, 2015, Rueckemann et al 2016, Zhao et al 2016) and featured comparatively simple behavioral tasks in larger environments. We did not observe any large-scale remapping or reductions in spatial information from transient MEC inactivation, in agreement with reports that the stability of hippocampal spatial maps can become independent of MEC or grid cell activity in familiar environments or those with rich proximal cues (Wang et al, 2015, Hales et al, 2014, Brandon et al 2014).…”

A Novel Mechanism for the Grid-to-Place Cell Transformation Revealed by Transgenic Depolarization of Medial Entorhinal Cortex Layer II

“…Even ideal surgical lesions are irreversible and temporally diffuse, as the brain gradually adapts to the insult. More recent work has shown that hippocampal place fields change their firing properties to varying degrees following pharmacological (Ormond and McNaughton, 2015), chemogenetic (Miao et al, 2015;Zhao et al, 2016), and optogenetic (Miao et al, 2015;Rueckemann et al, 2016) inactivation of MEC. While these results provide support for the idea that MEC is involved in hippocampal spatial firing, the changes in the firing patterns of MEC neurons in response to these manipulations are not well characterized.…”