A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory

Ben-Simon, Yoav; Kaefer, Karola; Velicky, Philipp; Csicsvari, Jozsef; Danzl, Johann G.; Jónás, Péter

doi:10.1038/s41467-022-32559-8

Cited by 17 publications

(22 citation statements)

References 78 publications

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“…In humans, commissural connections seem to be even more reduced ( Insausti and Amaral, 2012 ). Recently, Ben-Simon et al (2022) reported that excitatory neurons in layer 6b of the mouse EC project to all sub-regions of the hippocampal formation and receive input from the CA1, thalamus and claustrum. These connections are not included in this schematic figure.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical and psychological considerations in temporal lobe epilepsy

et al. 2022

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Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and is associated with a variety of structural and psychological alterations. Recently, there has been renewed interest in using brain tissue resected during epilepsy surgery, in particular ‘non-epileptic’ brain samples with normal histology that can be found alongside epileptic tissue in the same epileptic patients — with the aim being to study the normal human brain organization using a variety of methods. An important limitation is that different medical characteristics of the patients may modify the brain tissue. Thus, to better determine how ‘normal’ the resected tissue is, it is fundamental to know certain clinical, anatomical and psychological characteristics of the patients. Unfortunately, this information is frequently not fully available for the patient from which the resected tissue has been obtained — or is not fully appreciated by the neuroscientists analyzing the brain samples, who are not necessarily experts in epilepsy. In order to present the full picture of TLE in a way that would be accessible to multiple communities (e.g., basic researchers in neuroscience, neurologists, neurosurgeons and psychologists), we have reviewed 34 TLE patients, who were selected due to the availability of detailed clinical, anatomical, and psychological information for each of the patients. Our aim was to convey the full complexity of the disorder, its putative anatomical substrates, and the wide range of individual variability, with a view toward: (1) emphasizing the importance of considering critical patient information when using brain samples for basic research and (2) gaining a better understanding of normal and abnormal brain functioning. In agreement with a large number of previous reports, this study (1) reinforces the notion of substantial individual variability among epileptic patients, and (2) highlights the common but overlooked psychopathological alterations that occur even in patients who become “seizure-free” after surgery. The first point is based on pre- and post-surgical comparisons of patients with hippocampal sclerosis and patients with normal-looking hippocampus in neuropsychological evaluations. The second emerges from our extensive battery of personality and projective tests, in a two-way comparison of these two types of patients with regard to pre- and post-surgical performance.

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Section: Discussionmentioning

confidence: 99%

Neuroanatomical and psychological considerations in temporal lobe epilepsy

et al. 2022

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“…Quantification of cell numbers and channel overlap in retrograde labeling experiments was done using FIJI/ImageJ (Schindelin et al , 2012) on stack images. For quantification of input densities, the number of retrogradely labeled neurons was divided by the number of nuclei (DAPI + ) in target regions using a custom‐written script (https://github.com/sommerc/coloco3surf; Ben‐Simon et al , 2022). ACC input density z ‐scores were then calculated against the average density for all brain regions included in the calculation to generate a relative density value for each.…”

Section: Methodsmentioning

confidence: 99%

An accessory prefrontal cortex–thalamus circuit sculpts maternal behavior in virgin female mice

et al. 2022

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The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first-time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2 + / Galanin + neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC-CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first-time exposure to pups.

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“…The neural circuits involving MEC layer VI (MECVI) remain unclear. A recent study by Ben‐Simon et al (2022) demonstrated that excitatory neurons in MECVI are labeled with the marker of cortical layer VIb, termed MEC layer VIb. MEC layer VIb cells receive input from hippocampal CA1, thalamus, and claustrum, and they send their projections to hippocampal CA3/CA1/DG (Ben‐Simon et al, 2022).…”

Section: Neural Circuits In Ec‐hpc Networkmentioning

confidence: 99%

“…The neocortical VIb subplates neurons also express biomarkers like Ctgf, Nxph4, and Cplx3 (Hoerder‐Suabedissen et al, 2009, 2013; Hoerder‐Suabedissen & Molnar, 2013). Ben‐Simon et al found that MECVI neurons are labeled by the markers of neocortical VIb neurons, while the markers of neocortical VIa are not expressed in ECVI (Ben‐Simon et al, 2022), suggesting the similarity of cell‐type populations to neocortical layer VIb. A rabies‐based transsynaptic retrograde and Cre‐dependent AAV labeling experiments injecting into DG, CA3, and CA1 suggest that the MECVI neurons monosynaptically innervate all the subfields of the hippocampus including DG, CA3, and CA1 (Ben‐Simon et al, 2022).…”

Section: Role Of VI Excitatory Neuronsmentioning

confidence: 99%

“…However, further region-specific experiments are required, since the ablation is not only targeted to MECVI population but also other cortical Ctgf + population. MECVI neurons receive the projections from multiple brain regions, including the central cortical hub, claustrum, and provide output to all subregions of the HPC(Ben-Simon et al, 2022;Wang et al, 2017), showing the richness and diversity of information transfer through this pathway. These new findings are in contrast with the existing hypothesis on deep layers of EC which were thought to channelize the hippocampal output by selectively processing the information from hippocampus and subiculum and relaying it to the telencephalic structures.Recent studies from deep layers of EC (both V and VI) providing projections to/from the hippocampus suggest that deep layers could function to affect both the neocortex and the hippocampus simultaneously, proposing the need for identifying the functional role of the deep layers in memory.…”

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confidence: 99%

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Dissecting cell‐type‐specific pathways in medial entorhinal cortical‐hippocampal network for episodic memory

Osanai

Nair

Kitamura

2023

Journal of Neurochemistry

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Episodic memory, which refers to our ability to encode and recall past events, is essential to our daily lives. Previous research has established that both the entorhinal cortex (EC) and hippocampus (HPC) play a crucial role in the formation and retrieval of episodic memories. However, to understand neural circuit mechanisms behind these processes, it has become necessary to monitor and manipulate the neural activity in a cell‐type‐specific manner with high temporal precision during memory formation, consolidation, and retrieval in the EC‐HPC networks. Recent studies using cell‐type‐specific labeling, monitoring, and manipulation have demonstrated that medial EC (MEC) contains multiple excitatory neurons that have differential molecular markers, physiological properties, and anatomical features. In this review, we will comprehensively examine the complementary roles of superficial layers of neurons (II and III) and the roles of deeper layers (V and VI) in episodic memory formation and recall based on these recent findings.

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A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory

Cited by 17 publications

References 78 publications

Neuroanatomical and psychological considerations in temporal lobe epilepsy

Neuroanatomical and psychological considerations in temporal lobe epilepsy

An accessory prefrontal cortex–thalamus circuit sculpts maternal behavior in virgin female mice

Dissecting cell‐type‐specific pathways in medial entorhinal cortical‐hippocampal network for episodic memory

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