Downstream effects of hippocampal sharp wave ripple oscillations on medial entorhinal cortex layer V neurons in vitro

Abstract

The entorhinal cortex (EC) is a critical component of the medial temporal lobe (MTL) memory system. Local networks within the MTL express a variety of state-dependent network oscillations that are believed to organize neuronal activity during memory formation. The peculiar pattern of sharp wave-ripple complexes (SPW-R) entrains neurons by a very fast oscillation at ∼200 Hz in the hippocampal areas CA3 and CA1 and then propagates through the "output loop" into the EC. The precise mechanisms of SPW-R propagation and the resulting cellular input patterns in the mEC are, however, largely unknown. We therefore investigated the activity of layer V (LV) principal neurons of the medial EC (mEC) during SPW-R oscillations in horizontal mouse brain slices. Intracellular recordings in the mEC were combined with extracellular monitoring of propagating network activity. SPW-R in CA1 were regularly followed by negative field potential deflections in the mEC. Propagation of SPW-R activity from CA1 to the mEC was mostly monosynaptic and excitatory, such that synaptic input to mEC LV neurons directly reflected unit activity in CA1. Comparison with propagating network activity from CA3 to CA1 revealed a similar role of excitatory long-range connections for both regions. However, SPW-R-induced activity in CA1 involved strong recruitment of rhythmic synaptic inhibition and corresponding fast field oscillations, in contrast to the mEC. These differences between features of propagating SPW-R emphasize the differential processing of network activity by each local network of the hippocampal output loop. © 2016 Wiley Periodicals, Inc.

The content of hippocampal “replay”

“…A potential answer comes from a recent study in which hippocampal and entorhinal cortical activity was simultaneously monitored (Yamamoto & Tonegawa, 2017). During replay, the medial entorhinal cortex (MEC), which communicates bi-directionally with the hippocampus (Witter et al, 2000), can also display increases in ripple-band power (Roth et al, 2016;Yamamoto & Tonegawa, 2017). Indeed, replay has recently been …”

Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons

“…This may be particularly relevant during propagation of sharp wave‐ripple complexes from CA1 to deep layers of the EC (Roth et al . ). Regulation of axonal excitability by I NaP may be an important determinant of information flow in such network processes.…”

“…Indeed, this mechanism has been shown to underlie spiking of axons (Dugladze et al 2012) and somata (B€ ahner et al 2011) during high-frequency oscillations in vitro. This may be particularly relevant during propagation of sharp waveripple complexes from CA1 to deep layers of the EC (Roth et al 2016). Regulation of axonal excitability by I NaP may be an important determinant of information flow in such network processes.…”

TRPC channels are not required for graded persistent activity in entorhinal cortex neurons

“…Horizontal brain slices (450 μm thick) containing the hippocampus and EC were obtained from 3 to 4 month old mice using standard techniques (Roth, Beyer, Both, Draguhn, & Egorov, 2016 (Haas, Schaerer, & Vosmansky, 1979), superfused with ACSF at a rate of 1.5-2 mL/min, and maintained at 34 ± 1 C. Prior to electrophysiological recordings, slices were allowed to recover for at least 2 hr. Membrane potential was manually adjusted by intracellular injection of DC current through the recording electrode and held near firing threshold (approximately −60 mV) for suprathreshold conditions.…”