Processing of Hippocampal Network Activity in the Receiver Network of the Medial Entorhinal Cortex Layer V

Abstract

The interplay between hippocampus and medial entorhinal cortex (mEC) is of key importance for forming spatial representations. Within the hippocampal-entorhinal loop, the hippocampus receives context-specific signals from layers II/III of the mEC and feeds memory-associated activity back into layer V (LV). The processing of this output signal within the mEC, however, is largely unknown. We characterized the activation of the receiving mEC network by evoked and naturally occurring output patterns in mouse hippocampal-entorhinal cortex slices. Both types of glutamatergic neurons (mEC LVa and LVb) as well as fast-spiking inhibitory interneurons receive direct excitatory input from the intermediate/ventral hippocampus. Connections between the two types of excitatory neurons are sparse, and local processing of hippocampal output signals within mEC LV is asymmetric, favoring excitation of far projecting LVa neurons over locally projecting LVb neurons. These findings suggest a new role for mEC LV as a bifurcation gate for feedforward (telencephalic) and feedback (entorhinal-hippocampal) signal propagation.

Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex

“…Whereas in LEC, LVa neurons receive substantial input from LVb neurons, this projection is relatively weak in dorsal MEC. This difference in dorsal MEC, though unexpected in view of previous data including our own rabies tracing data (Ohara et al, 2018), has been recently corroborated in an in vitro study using paired-patch recording (Rozov et al, 2020), and our present corroborating tracing data are in line with previous tracing data in the rat (Köhler, 1986) and monkey (Chrobak and Amaral, 2007).…”

“…The effectiveness of functional connections may further be influenced by incoming inputs to LVa and/or LVb, such as those from the claustrum ( Kitamura et al, 2017 ), medial septum, medial prefrontal cortex, and retrosplenial cortex ( Ohara et al, 2018 ). Adding to this complexity is a recent report that there is a direct projection from the intermediate/ventral hippocampus to neurons in MEC LVa ( Rozov et al, 2020 ). To assess these complex interactions, further in vivo studies are clearly required.…”

Local projections of layer Vb-to-Va are more effective in lateral than in medial entorhinal cortex

“…Whereas in LEC, LVa neurons receive substantial input from LVb neurons, this projection is apparently weak to absent in dorsal MEC. The weak and sparse LVb-to-LVa projections in dorsal MEC, though unexpected in view of previous data including our own rabies tracing data (Ohara et al, 2018), has been recently corroborated in an in vitro study using paired-patch recording (Rozov et al, 2020), and our present corroborating tracing data are in line with previous tracing data in the rat (Köhler, 1986) and monkey (Chrobak and Amaral, 2007).…”

“…In contrast to the dorsal level, we showed at more ventral levels an increased LVb-to-LVa connectivity, in line with our previous study (Ohara et al, 2018). Interestingly, a recent study has reported that there is a direct projection from the intermediate/ventral hippocampus to neurons in MEC LVa (Rozov et al, 2020), indicating that the hippocampal-output pathway via MEC may differ along the dorsoventral axis. Our data in LEC show the presence of strong and effective connections from LVb to LVa, and this striking difference with MEC is also reflected in the observation that LVa, the entorhinal-output layer, is thicker in LEC than in MEC.…”

Telencephalic outputs from the medial entorhinal cortex are copied directly to the hippocampus

“…inputs from the dorsal hippocampus preferentially target L5b over L5a 6,12,13 . To find out whether neurons in either L5a or L5b project to the hippocampus we injected a retrograde adeno-associated viral vector (AAV) expressing green fluorescent protein (GFP) into intermediate CA1.…”