Proximodistal organization of the CA2 hippocampal area

Abstract

Competitividad (MINECO) to LMP (BFU2015-66887-R) and the Fundación Tatiana Perez de Guzman el Bueno. DGD and MV were supported by a PhD fellowship from the Spanish Ministry of Economy (BES-2013-064171) and from the Ministry of Education, Culture and Sports (FPU12/03776), respectively. We thank to the Deisseroth lab for sharing their optogenetic constructs. VGAT-Venus transgenic rats were generated by Drs. Y. Yanagawa, M. Hirabayashi, and Y.Kawaguchi at the National Institute for Physiological Sciences (Okazaki, Japan) using pCS2-Venus provided by Dr. A. Miyawaki. VGAT line progenitors were provided by the National Bioresource Project Rat (Kyoto, Japan) 2The proximodistal axis is considered a major organizational principle of the hippocampus. Interfacing between the hippocampus and other brain systems, the CA2 region apparently breaks this rule. Apart from its specific role in social memory, CA2 has been involved in temporal and contextual memory but mechanisms remain elusive. Here, we used intracellular and extracellular recordings followed by neurochemical identification of single-cells to evaluate CA2 and surrounding areas in the rat. We found marked proximodistal trends of synaptic activity, as well as in subthreshold membrane potentials and phase-locked firing coupled to theta and gamma oscillations. Opposite proximodistal correlations between membrane potential fluctuations and theta sinks and sources at different layers revealed influences from up to three different generators. CA2 memory engrams established after a social memory task reflected these trends. We suggest that the structure and function of CA2 is segregated along the proximodistal hippocampal axis.

CA2 inhibition reduces the precision of hippocampal assembly reactivation

“…As the majority of SWRs recruit high-frequency activity in all CA regions nearly simultaneously (Buzsaki, 2015;Oliva et al, 2016a;Stark et al, 2014;Sullivan et al, 2011), we next computed wavelet spectrograms of LFP recorded in each region, centered at the peak rippleband power (100-250 Hz) of events recorded in CA1. Consistent with prior evidence (Fernandez-Lamo et al, 2019;Oliva et al, 2016a), in control mice ripple power in CA1 was strongly aligned to the SWR peak ( Fig. 1f).…”

Parallel processing streams in the hippocampus

“…In experiments demonstrating pattern separation and pattern completion, CA2 was similar to distal CA3, performing pattern completion [22,23]. Distal CA2 cells fire in phase with the proximal CA1 cells and proximal CA2 cells fire in phase with the distal CA3 cells [72]. These results suggest that the CA2 region is more associated with the distal CA3-proximal CA1 stream, which is associated with the MEC pathway in processing the allocentric spatial representation.…”

How development sculpts hippocampal circuits and function

“…Interestingly, cells located in the subiculum or CA2, two subregions with an earlier temporal origin than CA1, also display a smaller Ih (163) (but see (234)), a lower Rm (129,163,234), higher excitability (207), and burst propensity (69). It should be noted that CA2 itself was recently shown to display significant heterogeneity along the proximo-distal axes (93), despite its overall earlier temporal origin compared to CA1 and CA3, possibly indicating the need for in depth examination of its embryonic developmental schedule. The diversity of intrinsic electrophysiological properties among CA3 PNs also distributes along the proximodistal axis, revealing a similar trend for Rm with the earlier born distal CA3 (CA3a) displaying a lower Rm than proximal CA3 cells (234).…”