Impaired path integration in mice with disrupted grid cell firing

Path integration (PI) is a highly conserved, self-motion-based navigation strategy. Since the discovery of grid cells in the medial entorhinal cortex, neurophysiological data and computational models have suggested that these neurons serve PI. However, more direct empirical evidence supporting this hypothesis has been missing due to a lack of selective manipulations of grid cell activity and suitable behavioral assessments. Here we report that selective disruption of grid cell activity in mice can be achieved by removing NMDA glutamate receptors from the retro-hippocampal region and that disrupted grid cell firing accounts for impaired PI performance. Notably, the genetic manipulation did not affect the activity of other spatially selective cells in the medial entorhinal cortex and the hippocampus. By directly linking grid cell activity to PI, these results contribute to a better understanding of how grid cells support navigation and spatial memory

The medial entorhinal cortex is necessary for temporal organization of hippocampal neuronal activity

The superficial layers of the medial entorhinal cortex (MEC) are the major input to the hippocampus. The high proportion of spatially modulated cells, including grid cells and border cells, in these layers suggests that the MEC inputs to the hippocampus are critical for the representation of space in the hippocampus. However, selective manipulations of the MEC do not completely abolish hippocampal spatial firing. To therefore determine whether other hippocampal firing characteristics depend more critically on MEC inputs, we recorded from hippocampal CA1 cells in rats with MEC lesions. Strikingly, theta phase precession was substantially disrupted, even during periods of stable spatial firing. Our findings indicate that MEC inputs to the hippocampus are required for the temporal organization of hippocampal firing patterns and suggest that cognitive functions that depend on precise neuronal sequences within the hippocampal theta cycle are particularly dependent on the MEC. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research

Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons

Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.Fil: Sasaki, Takuya. University of California at San Diego; Estados Unidos. The University of Tokyo; Japón. Japan Science and Technology Agency; JapónFil: Piatti, Veronica del Carmen. University of California at San Diego; Estados UnidosFil: Hwaun, Ernie. University of California at San Diego; Estados UnidosFil: Ahmadi, Siavash. University of California at San Diego; Estados UnidosFil: Lisman, John E.. Brandeis University; Estados UnidosFil: Leutgeb, Stefan. University of California at San Diego; Estados UnidosFil: Leutgeb, Jill K.. University of California at San Diego; Estados Unido