Intrinsic Projections of Layer Vb Neurons to Layers Va, III, and II in the Lateral and Medial Entorhinal Cortex of the Rat

Abstract

Layer V of the entorhinal cortex (EC) receives input from the hippocampus and originates main entorhinal outputs. The deep-sublayer Vb, immunopositive for the transcription factor Ctip2, is thought to be the main recipient of hippocampal projections, whereas the superficial-sublayer LVa, immunonegative for Ctip2, originates the main outputs of EC. This disrupts the proposed role of EC as mediating hippocampal-cortical interactions. With the use of specific (trans)synaptic tracing approaches, we report that, in medial entorhinal cortex, layer Vb neurons innervate neurons in layers Va, II, and III. A similar circuitry exists in the lateral entorhinal cortex. We conclude that EC-layer Vb neurons mediate two circuits in the hippocampus-memory system: (1) a hippocampal output circuit to telencephalic areas by projecting to layer Va and (2) a feedback projection, sending information back to the EC-hippocampal loop via neurons in layers II and III.

A characterization of the electrophysiological, morphological and input domains of vasoactive intestinal peptide (VIP) interneurons in the medial entorhinal cortex (MEC)

“…Moreover, we saw a gradient in this intrinsic excitability wherein cells located in ventral MEC require less current to fire an action potential compared to cells in dorsal MEC. The gradients in excitability that we report could provide a gating mechanism that prioritizes certain outputs from the MEC as deep MEC sends projections to various intrathalamic structures and LII of the MEC (Ohara et al, 2018;Sürmeli et al, 2015) whereas superficial MEC primarily projects to the hippocampus (Canto et al, 2008). This could also be relevant to the in vivo reports that grid cells with smaller spatial scales are present near the dorsal border while cells with a larger spatial scale are found more ventrally (Hafting et al 2005, Barry et al 2007, Brun et al 2008, Stensola et al 2012.…”

“…Our tracing experiments reveal that VIPs receive both local and long-range inputs thus providing for a dynamic routing of information to the MEC. Previous studies have shown that grid cells in LII of the MEC require hippocampal information to stabilize their firing fields (Bonnevie et al, 2013), and that this input is primarily received by cells in the deep layers , Ohara et al 2018. While cells from LVb project to the superficial layers (Ohara et al, 2018), our experiments revealed an additional route for this feedback to reach spatially tuned cells in layers II-III.…”

“…Previous studies have shown that grid cells in LII of the MEC require hippocampal information to stabilize their firing fields (Bonnevie et al, 2013), and that this input is primarily received by cells in the deep layers , Ohara et al 2018. While cells from LVb project to the superficial layers (Ohara et al, 2018), our experiments revealed an additional route for this feedback to reach spatially tuned cells in layers II-III. Additionally, VIP interneurons receive inputs from the Me5 an important component of the oromotor neural circuitry, jaw movement and mastication in mice.…”

Molecular Diversity Among Adult Human Hippocampal and Entorhinal Cells

“…Specifically, two layer 2 subtypes were classified as RELN + and one as CALB1 + (Witter et al, 2017). Other upper-layer subtypes were depicted based on marker gene expression of LAMA3 , PDGFD , IL1RAPL2 , and PCP4 (Ramsden et al, 2015; Tang et al, 2015; Ohara et al, 2018). The middle-to-deep layer subtypes were delineated by the specific gene expression of RORB , THEMIS , ADRA1A , and TLE4 .…”

Bcl11 Transcription Factors Regulate Cortical Development and Function

“…Both Bcl11 genes are expressed during embryonic development as early as E10.5 and continuing to be expressed throughout life in several tissues like the brain, immune system, and skin (Leid et al, 2004;Golonzhka et al, 2007;Zhang et al, 2012). In the central nervous system, Bcl11 genes are expressed in the dorsal spinal cord, neocortex, hippocampus, entorhinal cortex, striatum, amygdala, and cerebellum ( Table 1; Leid et al, 2004;Arlotta et al, 2005Arlotta et al, , 2008Desplats et al, 2008;John et al, 2012;Simon et al, 2012;Canovas et al, 2015;Surmeli et al, 2015;Wiegreffe et al, 2015;Greig et al, 2016;Woodworth et al, 2016;Ohara et al, 2018). The best studied brain areas in relation to Bcl11 are the hippocampus, neocortex, spinal cord, and striatum.…”