Abstract
SummaryThe hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory.
Highlights
The hippocampus is known to support both spatial navigation and episodic memory formation (Scoville and Milner, 1957; Morris et al, 1982; O’Keefe and Nadel, 1978; Ergorul and Eichenbaum, 2004)
Populations of hippocampal neurons exhibit sequences of firing fields that tile the continuous dimensions of experiences involving modalities other than space (Eichenbaum et al, 1987; Pastalkova et al, 2008; MacDonald et al, 2011; Villette et al, 2015; Allen et al, 2016; Terada et al, 2017; Aronov et al, 2017; Omer et al, 2018; Danjo et al, 2018), and one prevailing view is that the generation of these sequences supports the formation of detailed episodic memories
We found no increase in lick rate during Start-PC stimulation, non-place cell (Non-PC) stimulation, or no-stimulation control sessions (Figure 2F; p = 1, p = 0.49, and p = 0.84, n = 9, 10, and 12 sessions, respectively; Wilcoxon signed-rank test)
Summary
The hippocampus is known to support both spatial navigation and episodic memory formation (Scoville and Milner, 1957; Morris et al, 1982; O’Keefe and Nadel, 1978; Ergorul and Eichenbaum, 2004). Place cell populations form largely unique maps to represent a given environment (Leutgeb et al, 2004; Alme et al, 2014) and remap, altering their firing properties in response to changes in that environment (Muller and Kubie, 1987; Bostock et al, 1991). Their reorganization to goal locations and subsequent reactivation predict spatial memory performance (Dupret et al, 2010; Xu et al, 2019) and the replay of place cell firing sequences (Skaggs and McNaughton, 1996; Lee and Wilson, 2002; Foster and Wilson, 2006; Diba and Buzsaki, 2007) has been linked to memory consolidation and retrieval (Girardeau et al, 2009; Jadhav et al, 2012; Fernandez-Ruiz et al, 2019; Norman et al, 2019). The substantial body of place cell research is predominantly correlational; recent work has moved toward providing a direct link to their proposed function
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