Molecularly Defined Circuitry Reveals Input-Output Segregation in Deep Layers of the Medial Entorhinal Cortex

Sürmeli, Gülşen; Marcu, Daniel-Cosmin; McClure, Christina; Garden, Derek L. F.; Pastoll, Hugh; Nolan, Matthew F.

doi:10.1016/j.neuron.2016.11.011

Cited by 25 publications

(50 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2e,f), proving the monosynaptic nature of the synaptic input. In contrast, and consistent with previous reports 10 , layer 5A neurons did not receive inputs from subicular burst-firing neurons (Figure 2d; Mann-Whitney test p<0.01).…”

Section: Main Textsupporting

confidence: 93%

“…Previously, subicular neurons have been shown to project to the deep layers of the entorhinal cortex 9 . More recently the wiring has been refined demonstrating that subicular (and CA1) pyramidal neurons project onto Coup-TF interacting protein 2 (CTIP2)-expressing neurons located in layer 5b of the EC 10 . However, whether these subicular neurons express VGLUT2 is unclear.…”

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

VGLUT2 functions as a differential marker for hippocampal output neurons

Wozny

Beed

Nitzan

et al. 2018

Preprint

View full text Add to dashboard Cite

1The subiculum is the gatekeeper between the hippocampus and cortical areas. Yet, the lack 2 of a pyramidal cell-specific marker gene has made the analysis of the subicular area very 3 difficult. Here we report that the vesicular-glutamate transporter 2 (VGLUT2) functions as a 4 specific marker gene for subicular burst-firing neurons, and demonstrate that VGLUT2-Cre 5 mice allow for Channelrhodopsin-2 (ChR2)-assisted connectivity analysis. 6 7 157

show abstract

Section: Main Textsupporting

confidence: 93%

Section: Main Textmentioning

confidence: 99%

VGLUT2 functions as a differential marker for hippocampal output neurons

Wozny

Beed

Nitzan

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…This organization prevails across the whole mediolateral and dorsoventral extent of EC. In both MEC and LEC, Layer Va cells are the major output neurons projecting to diverse cortical and subcortical structures (Kosel et al, ; Ohara et al, ; Ramsden, Surmeli, McDonagh, & Nolan, ; Surmeli et al, ; Swanson & Köhler, ; G. W. van Hoesen, ). Surprisingly, Layer Vb cells are selectively targeted by the outputs from the hippocampus, originating in CA1 and subiculum (Surmeli et al, ), though this is apparently only true for projections originating from dorsal levels of subiculum and CA1; increasingly more ventral levels apparently innervate neurons in both Layer Va and Vb (Egorov, Lorenz, Rozov, & Draguhn, ; Ohara and Witter, unpublished data).…”

Section: Introductionmentioning

confidence: 99%

“…In both MEC and LEC, Layer Va cells are the major output neurons projecting to diverse cortical and subcortical structures (Kosel et al, ; Ohara et al, ; Ramsden, Surmeli, McDonagh, & Nolan, ; Surmeli et al, ; Swanson & Köhler, ; G. W. van Hoesen, ). Surprisingly, Layer Vb cells are selectively targeted by the outputs from the hippocampus, originating in CA1 and subiculum (Surmeli et al, ), though this is apparently only true for projections originating from dorsal levels of subiculum and CA1; increasingly more ventral levels apparently innervate neurons in both Layer Va and Vb (Egorov, Lorenz, Rozov, & Draguhn, ; Ohara and Witter, unpublished data). Layer Vb neurons in both LEC and MEC innervate Layer Va as well as Layers II and III (Ohara et al, ), corroborating older data that neurons in Layer Vb issue superficially directed axon collaterals (Canto & Witter, , ; Hamam et al, ; Hamam et al, ).…”

Section: Introductionmentioning

confidence: 99%

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

et al. 2019

View full text Add to dashboard Cite

In this review, we aim to reappraise the organization of intrinsic and extrinsic networks of the entorhinal cortex with a focus on the concept of parallel cortical connectivity streams. The concept of two entorhinal areas, the lateral and medial entorhinal cortex, belonging to two parallel input–output streams mediating the encoding and storage of respectively what and where information hinges on the claim that a major component of their cortical connections is with the perirhinal cortex and postrhinal or parahippocampal cortex in, respectively, rodents or primates. In this scenario, the lateral entorhinal cortex and the perirhinal cortex are connectionally associated and likewise the postrhinal/parahippocampal cortex and the medial entorhinal cortex are partners. In contrast, here we argue that the connectivity matrix emphasizes the potential of substantial integration of cortical information through interactions between the two entorhinal subdivisions and between the perirhinal and postrhinal/parahippocampal cortices, but most importantly through a new observation that the postrhinal/parahippocampal cortex projects to both lateral and medial entorhinal cortex. We suggest that entorhinal inputs provide the hippocampus with high‐order complex representations of the external environment, its stability, as well as apparent changes either as an inherent feature of a biological environment or as the result of navigating the environment. This thus indicates that the current connectional model of the parahippocampal region as part of the medial temporal lobe memory system needs to be revised.

show abstract

“…), providing projections to principal cells in MEC layer V (Surmeli et al . ), as well as long‐range projections to the dentate gyrus and CA3 regions of the hippocampus (van Strien et al . ), making them ideally suited to coordinate and distribute grid and other spatial signals.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D2 receptors regulate the action potential threshold by modulating T‐type calcium channels in stellate cells of the medial entorhinal cortex

Jin

Chen

Song

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

Key pointsr Activation of axonal dopamine D2 receptors (D2Rs) increases action potential (AP) threshold, and thus decreases neuronal excitability in layer II stellate cells of medial entorhinal cortex.r Endogenous dopamine release increases the AP threshold of stellate cells by activating D2Rs. r Activation of D2Rs shifts the activation curve of T-type Ca 2+ channels in a positive direction in a protein kinase A-dependent manner.r Immunofluorescence staining reveals the presence of T-type Ca 2+ channels and D2Rs in the axon initial segments (AISs).r This research makes the pioneering discovery of D2R-induced AP threshold plasticity in AISs of stellate cells. The findings are likely to have significant implications for understanding the cellular processes by which dopamine influences neuronal intrinsic excitability.Abstract Stellate cells in the medial entorhinal cortex (MEC) are considered to constitute the largest population of grid cells, which provide spatial representation to support animal estimation of location. Although dopaminergic fibres from the ventral tegmental area and substantia nigra pars compacta innervate the majority of the cortex, including the MEC, little is known about how dopamine modulates the function of MEC stellate cells. Because dopamine D2 receptors (D2Rs) are involved in spatial cognition and MEC contains high levels of D2Rs, we investigated how D2R activation modulates the neuronal intrinsic excitability of stellate cells. Electrophysiological Xueqin Jin received her bachelor's degree in Pharmaceutical Science in 2014 from Jilin University. Currently, she is a PhD student in the School of Pharmaceutical Sciences at Peking University under the supervision of Prof. Zhuo Huang. She is now focusing on how neurotransmitters modulate neuronal functional plasticity in spatial cognition and working memory.3364 X. Jin and others J Physiol 597.13recordings, optogenetics and molecular biology experiments were performed to investigate the mechanism in mice. Activation of axonal D2Rs, not dendritic or somatic D2Rs, elevated the action potential (AP) threshold and decreased the intrinsic excitability of stellate cells, which was caused by shifting rightward the activation properties of T-type Ca 2+ channels in a D2R-protein kinase A-dependent manner without affecting their steady-state inactivation curve. In support, immunofluorescence assays revealed colocalization of D2Rs and Ca v 3.2 calcium channels within the axon initial segment. These findings are likely to have significant implications for understanding the cellular processes by which dopamine influences neuronal excitability and they may also be applicable to other hippocampal and cortical regions as dopaminergic fibres innervate wide brain regions. Taken together, these findings provide a novel cellular mechanism by which D2Rs modulate AP threshold of stellate cells through T-type Ca 2+ channels in MEC, indicating that D2Rs of MEC play a vital role in modulating the information processing of stellate cells.

show abstract

Molecularly Defined Circuitry Reveals Input-Output Segregation in Deep Layers of the Medial Entorhinal Cortex

Cited by 25 publications

References 0 publications

VGLUT2 functions as a differential marker for hippocampal output neurons

VGLUT2 functions as a differential marker for hippocampal output neurons

Neurons and networks in the entorhinal cortex: A reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways

Dopamine D2 receptors regulate the action potential threshold by modulating T‐type calcium channels in stellate cells of the medial entorhinal cortex

Contact Info

Product

Resources

About