Fig. 6. LEC-mediated long-range gamma synchrony is essential for cortical memory-related neurons reactivation and memory retrieval in HPC-intact mice.
a Experimental scheme for LEC inhibition by hM4D(Gi) in spatial memory recall and retraining to test if LEC is essential for successful memory recall. b–c Inhibition of LEC activity impair memory recall. b Occupancy in the food zone significantly decreased in recall trail (N = 15 mice, two-sided paired t-test, t(14) = 3.5, P = 0.0036). c Latency to the reward in the following retraining trail increased (N = 15 mice, two-sided paired t-test, t(14) = 3.2, P = 0.0067), CNO dosage: 2 mg/kg. d Similar to Fig. 5a, experimental scheme shows calcium signals from labeled neurons (labeled in training day4) and LFPs were recorded simultaneously during memory recall with or without LEC inhibition. e Left, calcium signal examples of labeled neurons in RSC and VIS with or without LEC inhibition. Right, quantification of CEs frequency in pre-exploring phase of memory recall (N total = 8 mice with three recorded in VIS and 5 in RSC, two-sided paired t-test, t(7) = 3.5, P = 0.0105). Red and blue dots indicate the peaks of the detected RSC and VIS calcium events, respectively. f Examples of LFPs around calcium events from the pre-exploring phase of recall trials with PBS and with CNO, the black bar above LFPs indicate the time range from rising time to the peak of the calcium event, illustrating theta (θ) and gamma (γ) LFPs transiently synchronized with zero-phase lag at the rising time of the calcium event while it is not the case in CNO administration recall trial. g Averaged synchrony (RSC-VIS) spectrogram, spectrograms were aligned to each peak of RSC or VIS calcium events in the pre-exploring phase during memory recall with or without LEC inhibition. (NPBS = 90 CEs, NCNO = 75 CEs, from six animals). h Change in low gamma synchrony in panel g (averaged PLV from −2s to 0 s) was quantified for each mouse. LEC inhibition impaired the coupling between engram activity and cortical low gamma synchronization (N total = 6 mice, paired two-sided t-test, t(5) = 3.541, P = 0.0165). i Cross-correlation analysis. Averaged correlation coefficient between low gamma synchrony and RSC or VIS engram activity in pre-exploring phase with CNO administration (red, N = 6 mice) or not (black, N = 6 mice). *P < 0.05. j Model for the mechanism in which long-range cortical gamma synchrony mediates memory encoding and retrieval by HPC/LEC. The illustration shows that the cortical long-range gamma synchrony is coupled to the theta wave and engram activities. Such a process might underlie hippocampus-mediated memory encoding and recall in the neocortex in a highly coordinated way. Engram coding partial context information in each cortical region was integrated by gamma synchronization and this integration contribute to intact memory representations.