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

Abstract

Complex spatial working memory (WM) 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 WM by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent WM task on an 8-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.

Differential propagation of ripples along the proximo-distal and septo-temporal axes of dorsal CA1 of rats

“…There are multiple potential candidates that may account for input asymmetry. The dentate gyrus (Sasaki et al, 2018;Sullivan et al, 2011), CA2 (Oliva et al, 2016a), and GABAergic projections from the medial septum (Dragoi et al, 1999;Viney et al, 2013) have been implicated in sharp-wave ripple initiation. Paucity of data about the projection patterns of these regions onto CA1 restricts our ability to understand their possible role in our observations.…”

Adult neurogenesis promotes efficient, nonspecific search strategies in a spatial alternation water maze task

“…Numerous electrophysiological studies have revealed that hippocampal neurons encode sequences of spatial locations [15]. Both hippocampal pyramidal and granule neurons encode prospective information as rats plan future navigational behaviors [48][49][50][51]. Adult neurogenesis may therefore be involved in navigational planning, which is supported by recent evidence that new neurons promote choice of advantageous, but delayed, rewards.…”

Quantitative properties of a feedback circuit predict frequency-dependent pattern separation

“…A recent model has addressed how fast, rhythmic gamma-frequency feedback inhibition may implement a type of 'k-winners-take-all' operation, a basic computational component of pattern separation models 60 , though this model relies on faster synaptic timescales than we observed in our compound IPSCs. Perhaps most interestingly, the occurrence of oscillations in the slow-gamma range has recently been reported to be causally related to associative memory formation 41,44 , a process thought to require pattern separation. Consistent with this finding, Hsiao et al 43 report DG driven gamma entrainment of CA3, the presumed primary storage location of associative memories.…”

“…It is furthermore necessary to quantify the spatial and temporal properties of the elicited inhibition, in order to investigate its impact on biologically plausible, temporally structured input. For instance, the DG shows prominent theta oscillations during exploration and distinctive slow-gamma activity during associative memory encoding [41][42][43][44] .…”

“…Specifically, we created input trains with constant mean rate, but with either theta (10 Hz) or slow-gamma (30 Hz) modulation ( Supplementary Figs. 6C, 7A), which are prominent during exploration and novelty exposure respectively 41,44 . To model rapid pattern separation in behaviorally relevant timescale we chose an input duration of approximately five theta cycles (600ms, corresponding to the approximate duration of place cell spiking during traversal of its place field).…”