Bilateral Synchronization of Hippocampal Early Sharp Waves in Neonatal Rats

Abstract

In the neonatal rodent hippocampus, the first and predominant pattern of correlated neuronal network activity is early sharp waves (eSPWs). Whether and how eSPWs are organized bilaterally remains unknown. Here, using simultaneous silicone probe recordings from the left and right hippocampus in neonatal rats in vivo we found that eSPWs are highly synchronized bilaterally with nearly zero time lag between the two sides. The amplitudes of eSPWs in the left and right hippocampi were also highly correlated. eSPWs also supported bilateral synchronization of multiple unit activity (MUA). We suggest that bilateral correlated activity supported by synchronized eSPWs participates in the formation of bilateral connections in the hippocampal system.

Keywords: bilateral; hippocampus; neonate; sharp waves; synchronization.

Figure 1

Interhemispheric synchronization of hippocampal early sharp waves (eSPWs) in neonatal rats. (A) Top: the microphotograph of DiI traces at insertion sites of two silicone probes on the surface of the left (L) and right (R) brain hemispheres in a P6 rat pup. Middle—Bottom: recording sites of 16-channel probes overlaid on cresyl violet stained coronal slices of the left (LH, middle) and right (RH, bottom) hippocampi. (B) Simultaneous local field potential (LFP) and multiple unit activity (MUA) recordings from the left hippocampus and right hippocampi from CA1 pyramidal cell layer (pcl, recording sites #3 and #19 on panel A) and strata lacunosum-moleculare (sl-m, recording sites #9 and #26 on panel A). Black arrows above the traces indicate eSPWs. Bottom, overlaid sl-m LFP traces from left (blue) and right (red) hippocampus. (C) The eSPW from panel (B; red asterisk) and average left eSPW-triggered LFP in the left and right hippocampus on expanded time scale. (D) Left eSPWs-triggered LFPs (black) in the left and right hippocampi overlaid on CSD maps. (E) Left eSPW onset-triggered raster plot of right eSPW onsets. (F) Left eSPW onset-triggered normalized PETH of right eSPW onsets (red) and corresponding z-score values (green). Group averages (mean ± SD; n = 6 animals) show the peak value of normalized PETH (red circle), the peak value of z-score (green circle) and the time lag between left and right eSPWs (black circle). (G) Five example traces of eSPWs recorded simultaneously in CA1 sl-m of left (blue) and right (red) hippocampi. (H) Relationships between left and right eSPW amplitudes recorded in CA1 sl-m layer (animal #2). Average amplitude values are indicated by an open circle with error bars corresponding to SD. Red arrows indicate the data points (outlined with red) corresponding to eSPWs shown on panel (G). See also Supplementary Figure S1 for all animals. (I) Amplitude averages of eSPWs in the left (blue) and right (red) hippocampi of six P5–7 rats (closed circles) and group values (open circles). Error bars show SD.

Figure 2

Bilateral synchronization of CA1 MUA during eSPWs. (A) Left eSPW onset-triggered raster plot of CA1 pcl MUA in the left (blue dots) and right (red dots) hippocampus. (B) Left eSPW onset-triggered and normalized to the baseline MUA peri-event time histograms (PETHs) in left and right hippocampi (top), corresponding MUA z-scores (middle) and average LFP (bottom). (C) Normalized cross-correlograms of MUA in right vs. left hippocampus within the time window of eSPWs (left) and during non-eSPW epochs (right). Cross-correlograms were normalized to the maximum value during eSPW epochs. (B,C) Group averages from three animals. Shaded areas show confidence intervals. MUA PETHs, z-scores and cross-correlograms were smoothed using a 20 ms-long sliding window.