Electrophysiological and morphological characterization of cells in superficial layers of rat presubiculum

Abstract

The presubiculum (PrS) plays critical roles in spatial information processing and memory consolidation and has also been implicated in temporal lobe epileptogenesis. Despite its involvement in these processes, a basic structure-function analysis of PrS cells remains far from complete. To this end, we performed whole-cell recording and biocytin labeling of PrS neurons in layer (L)II and LIII to examine their electrophysiological and morphological properties. We characterized the cell types based on electrophysiological criteria, correlated their gross morphology, and classified them into distinct categories using unsupervised hierarchical cluster analysis. We identified seven distinct cell types: regular-spiking (RS), irregular-spiking (IR), initially bursting (IB), stuttering (Stu), single-spiking (SS), fast-adapting (FA), and late-spiking (LS) cells, of which RS and IB cells were common to LII and LIII, LS cells were specific to LIII, and the remaining types were identified exclusively in LII. Recorded neurons were either pyramidal or nonpyramidal and, except for Stu cells, displayed spine-rich dendrites. The RS, IB, and IR cells appeared to be projection neurons based on extension of their axons into LIII of the medial entorhinal area (MEA) and/or angular bundle. We conclude that LII and LIII of PrS are distinct in their neuronal populations and together constitute a more diverse population of neurons than previously suggested. PrS neurons serve as major drivers of circuits in superficial (LII-III) entorhinal cortex (ERC) and couple neighboring structures through robust afferentation, thereby substantiating the PrS's critical role in the parahippocampal region.

Layer-Specific Organization of Local Excitatory and Inhibitory Synaptic Connectivity in the Rat Presubiculum

“…In fact, these cells exhibited electrophysiological properties similar to those of pyramidal cells, but had a more depolarized RMP (bursting PC −64.6 ± 1.9 mV vs. regular PC −73.3 ± 0.4 mV, P < 0.001) in good agreement with previous reports (Simonnet et al 2013). In contrast to previous studies, however, we found these bursting neurons throughout all layers and not restricted to layer IV (Simonnet et al 2013) or superficial layers (Abbasi and Kumar 2013). …”

“…There is increasing knowledge about the diversity of cell types in the presubiculum (Abbasi and Kumar 2013; Simonnet et al 2013; Nassar et al 2015; Preston-Ferrer et al 2016), but little is known about its network topology. In the presubiculum, layers I to III are usually referred to as superficial layers and layers V and VI as deep layers.…”

“…The intrinsic properties of excitatory and inhibitory cells in the presubiculum have been studied in rats and mice (Abbasi and Kumar 2013; Simonnet et al 2013; Nassar et al 2015; Preston-Ferrer et al 2016). Classification of pyramidal cells based on intrinsic electrophysiological properties revealed a majority of regular spiking cells in both superficial and deep layers (Abbasi and Kumar 2013; Simonnet et al 2013) and a smaller population of intrinsic bursting cells either restricted to layer IV (Simonnet et al 2013) or distributed in the superficial layers (Abbasi and Kumar 2013).…”

“…Classification of pyramidal cells based on intrinsic electrophysiological properties revealed a majority of regular spiking cells in both superficial and deep layers (Abbasi and Kumar 2013; Simonnet et al 2013) and a smaller population of intrinsic bursting cells either restricted to layer IV (Simonnet et al 2013) or distributed in the superficial layers (Abbasi and Kumar 2013). Recent in vivo studies have discovered further diversity of pyramidal cell in layers II and III with respect to their calbindin-expression, target-specific projections, theta rhythmicity and modulation by head direction (Preston-Ferrer et al 2016).…”

Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy

“…The reduced inhibitory synaptic drive noted in LII stellate cells under epileptic conditions (Kobayashi et al 2003;Kumar et al 2007;Tolner et al 2007) is consistent with diminution of PrS-mediated synaptic inhibition arising in part from either loss of GABAergic neurons in PrS, including MEA-targeting projection neurons (Drexel et al 2012;van Vliet et al 2004), loss of local GABAergic interneurons in MEA (Kumar and Buckmaster 2006;van Vliet et al 2004) and/or downregulation of GABA subunits mediating tonic inhibition (Drexel et al 2013). The loss of GABAergic neurons in PrS is substantiated by the absence of stuttering cells in epileptic rats (Abbasi and Kumar 2013;Abbasi and Kumar 2014 new synapses between target-deprived afferents from PrS and surviving LIII neurons (Scharfman et al 1998;Tolner et al 2005). Our data with focal application of glutamate in the PrS however did not indicate an increased PrS influence of surviving LIII pyramidal neurons in MEA.…”