Proximodistal Organization of the CA2 Hippocampal Area

Abstract

Summary The proximodistal axis is considered a major organizational principle of the hippocampus. At the interface between the hippocampus and other brain structures, CA2 apparently breaks this rule. The region is involved in social, temporal, and contextual memory function, but mechanisms remain elusive. Here, we reveal cell-type heterogeneity and a characteristic expression gradient of the transcription factor Sox5 within CA2 in the rat. Using intracellular and extracellular recordings followed by neurochemical identification of single cells, we find marked proximodistal trends of synaptic activity, subthreshold membrane potentials, and phase-locked firing coupled to theta and gamma oscillations. Phase-shifting membrane potentials and opposite proximodistal correlations with theta sinks and sources at different layers support influences from different current generators. CA2 oscillatory activity and place coding of rats running in a linear maze reflect proximodistal state-dependent trends. We suggest that the structure and function of CA2 are distributed 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 ripple- band 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 ).…”

Structural Correlates of CA2 and CA3 Pyramidal Cell Activity in Freely-Moving Mice

“…Hippocampal Pyr neurons have been classically assumed to be a relatively homogeneous population; however, recent work has demonstrated that their structural and functional properties change systematically according to topographical position (Ishizuka et al, 1995;Nakamura et al, 2013;H. Lee et al, 2015;Lu et al, 2015;Oliva et al, 2016;Sun et al, 2017;Fernandez-Lamo et al, 2019;Raus Balind et al, 2019). Specifically, in vivo extracellular work has shown that, on average, the tendency of neurons to fire spikebursts changes gradually along the CA2/CA3 proximodistal axis (Oliva et al, 2016), in line with the graded changes in neuronal morphology, input-output connectivity, intrinsic properties, and molecular expression profiles (Ishizuka et al, 1995;Sun et al, 2017;Fernandez-Lamo et al, 2019).…”

“…Lee et al, 2015;Lu et al, 2015;Oliva et al, 2016;Sun et al, 2017;Fernandez-Lamo et al, 2019;Raus Balind et al, 2019). Specifically, in vivo extracellular work has shown that, on average, the tendency of neurons to fire spikebursts changes gradually along the CA2/CA3 proximodistal axis (Oliva et al, 2016), in line with the graded changes in neuronal morphology, input-output connectivity, intrinsic properties, and molecular expression profiles (Ishizuka et al, 1995;Sun et al, 2017;Fernandez-Lamo et al, 2019). Notably, even within the same topographical level, Pyr neurons are heterogeneous, thus raising the possibility that different neuronal morphologies could show distinct tendencies to fire spike-bursts, as supported by recent work in vitro (Marissal et al, 2012;Raus Balind et al, 2019) and in the anesthetized brain (Hunt et al, 2018).…”

Methods for single-cell recording and labeling in vivo

“…This technique allows accessing the intracellular membrane potential, thus providing information not only about neuronal firing (spikes > 50-60 mV) but also on subthreshold synaptic activity. Different cell types, including glial cells, can be recorded with this method (Kelly and Van Essen, 1974) (English et al, 2014;Fernandez-Lamo et al, 2019;Kamondi et al, 1998;Quilichini et al, 2010;Sik et al, 1995;Steriade et al, 2001;Valero et al, 2015;Ylinen et al, 1995). Sharp recordings are blind by definition and the ability to impale a cell depends on a combination of factors.…”

“…In some cases, using electrical stimulation of input pathways may help to guide penetration by evoked potentials. Others learn to functionally characterize the cell-type of interest beforehand by establishing critical hallmarks using electrical or optogenetic stimulation to disclose projecting cells (Steriade et al, 1993a,b;Fernandez-Lamo et al, 2019).…”