Menno P Witter

Menno P Witter
Norwegian University of Science and Technology | NTNU · Kavli Institute for Systems Neuroscience and Centre for Neural Computation

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376
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Publications

Publications (376)
Article
Full-text available
Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we rev...
Preprint
Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and in vitro electrophysiology in mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the d...
Article
In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subregions using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity se...
Preprint
Full-text available
Throughout mammalian evolution, the hippocampal region, unlike the neocortex, largely preserved its cytoarchitectural organization and its role in mnemonic functions. This contrast raises the possibility that the hippocampal region receives different types of cortical input across species, which may be reflected in species-specific memory-related d...
Preprint
Throughout mammalian evolution, the hippocampal region, unlike the neocortex, largely preserved its cytoarchitectural organization and its role in mnemonic functions. This contrast raises the possibility that the hippocampal region receives different types of cortical input across species, which may be reflected in species-specific memory-related d...
Preprint
The claustrum is thought to be one of the most highly interconnected forebrain structures but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons to understand how the structure’s unique convergence of input and diverge...
Preprint
The claustrum is thought to be one of the most highly interconnected forebrain structures but its organizing principles have yet to be fully explored at the level of single neurons. Here, we investigated the identity, connectivity, and activity of identified claustrum neurons to understand how the structure’s unique convergence of input and diverge...
Preprint
Full-text available
Throughout mammalian evolution, the hippocampal region, unlike the neocortex, largely preserved its cytoarchitectural organization and its role in mnemonic functions. This contrast raises the possibility that the hippocampal region receives different types of cortical input across species, which may be reflected in species-specific memory-related d...
Article
GABAergic neurons represent 10–15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin‐expressing fast‐spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the de...
Article
Full-text available
Accurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cell-type. We recently used enhancers, the subcompone...
Article
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The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer’s disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimagin...
Preprint
Full-text available
GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing (PV-INs) fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recentl...
Article
Full-text available
Accurate anatomical characterizations are necessary to investigate neural circuitry on a fine scale, but for the rodent claustrum complex (CLCX), this has yet to be fully accomplished. The CLCX is generally considered to comprise two major subdivisions, the claustrum (CL) and the dorsal endopiriform nucleus (DEn), but regional boundaries to these a...
Article
Full-text available
The orbitofrontal, posterior parietal, and insular cortices are sites of higher-order cognitive processing implicated in a wide range of behaviours, including working memory, attention guiding, decision making, and spatial navigation. To better understand how these regions contribute to such functions, we need detailed knowledge about the underlyin...
Article
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Background: Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,...
Preprint
Engineered biological neural networks are indispensable tools for investigating neural function in both healthy and diseased states from the subcellular to the network level. Neurons in vitro self-organize over time into networks of increasing structural and functional complexity, thus maintaining emergent dynamics of neurons in the brain. While in...
Article
Full-text available
Tract-tracing studies in primates indicate that different subregions of the medial temporal lobe (MTL) are connected with multiple brain regions. However, no clear framework defining the distributed anatomy associated with the human MTL exists. This gap in knowledge originates in notoriously low MRI data quality in the anterior human MTL and in gro...
Article
Risk and resilience for neuropsychiatric illnesses are established during brain development, and transcriptional markers of risk may be identifiable in early development. The dorsal-ventral axis of the hippocampus has behavioral, electrophysiological, anatomical, and transcriptional gradients and abnormal hippocampus development is associated with...
Article
Full-text available
Introduction: The mammalian visual system can be broadly divided into two functional processing pathways: a dorsal stream supporting visually and spatially guided actions, and a ventral stream enabling object recognition. In rodents, the majority of visual signaling in the dorsal stream is transmitted to frontal motor cortices via extrastriate vis...
Article
Full-text available
The dense fiber pathways that connect the insular cortex with frontal cortices are thought to provide these frontal areas with interoceptive information, crucial for their involvement in executive functions. Using anterograde neuroanatomical tracing, we mapped the detailed organization of the projections from the rat insular cortex to its targets i...
Article
Full-text available
Projection neurons in the anteriolateral part of entorhinal cortex layer II are the predominant cortical site for hyperphosphorylation of tau and formation of neurofibrillary tangles in prodromal Alzheimer’s disease. A majority of layer II projection-neurons in anteriolateral entorhinal cortex are unique among cortical excitatory neurons by express...
Article
The hippocampal formation and entorhinal cortex are crucially involved in learning and memory as well as in spatial navigation. The conservation of these structures across the entire mammalian lineage demonstrates their importance. Information on a diverse set of spatially tuned neurons has become available, but we only have a rudimentary understan...
Article
Full-text available
Previous research has emphasized the unique impact of Alzheimer’s Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases...
Article
Background: Primary neuronal cultures enable cell-biological studies of Alzheimer's disease (AD), albeit typically non-neuron-specific. The first cortical neurons affected in AD reside in layer II of the lateralmost part of the entorhinal cortex, and they undergo early accumulation of intracellular amyloid-β, form subsequent tau pathology, and sta...
Article
The general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projectio...
Preprint
Full-text available
In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subdivision using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity s...
Article
Full-text available
Reconstructing dense 3D anatomical coordinates from 2D projective measurements has become a central problem in digital pathology for both animal models and human studies. Here we describe Projective Large Deformation Diffeomorphic Metric Mapping (LDDMM), a technique which projects diffeomorphic mappings of dense human magnetic resonance imaging (MR...
Preprint
Full-text available
The mammalian visual system can be broadly divided into two functional processing pathways: a dorsal stream supporting visually and spatially guided actions, and a ventral stream enabling object recognition. In rodents, the majority of visual signaling in the dorsal stream is transmitted to frontal motor cortices via extrastriate visual areas surro...
Preprint
Full-text available
Background: Primary neuronal cultures enable cell-biological studies of Alzheimer's disease (AD), albeit typically non-neuron-specific. The first cortical neurons affected in AD reside in layer II of the lateralmost part of the entorhinal cortex, and they undergo early accumulation of intracellular amyloid-β, form subsequent tau pathology, and star...
Preprint
Full-text available
Functionally distinct information encoded by the two main divisions of the entorhinal cortex (EC), the lateral EC (LEC) and the medial EC (MEC), is thought to be first integrated at the level of the hippocampus. Here we examine a circuit connecting MEC to LEC that supports functional interplay at the level of the two entorhinal domains. Using a com...
Article
Full-text available
The medial entorhinal cortex (MEC) plays a pivotal role in spatial processing together with hippocampal formation. The retrosplenial cortex (RSC) is also implicated in this process, and it is thus relevant to understand how these structures interact. This requires precise knowledge of their connectivity. Projections from neurons in RSC synapse onto...
Article
Full-text available
The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris...
Article
Full-text available
Stellate cells are principal neurons in the entorhinal cortex that contribute to spatial processing. They also play a role in the context of Alzheimer’s disease as they accumulate Amyloid beta early in the disease. Producing human stellate cells from pluripotent stem cells would allow researchers to study early mechanisms of Alzheimer’s disease, ho...
Preprint
One of the neuropathological hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid-β (Aβ) plaques, which is preceded by intraneuronal build-up of toxic, aggregated Aβ during disease progression. Aβ plaques are first deposited in the neocortex before appearing in the medial temporal lobe, and tau pathology with subsequent neurodegener...
Article
Full-text available
The ability to encode and retrieve contextual information is an inherent feature of episodic memory that starts to develop during childhood. The postrhinal cortex, an area of the parahippocampal region, has a crucial role in encoding object-space information and translating egocentric to allocentric representation of local space. The strong connect...
Preprint
Previous research has emphasized the unique impact of Alzheimer’s Disease (AD) pathology on the medial temporal lobe (MTL), a reflection that tau pathology is particularly striking in the entorhinal and transentorhinal cortex (ERC, TEC) early in the course of disease. However, other brain regions are affected by AD pathology during its early phases...
Preprint
Full-text available
Accurate anatomical characterizations are necessary to investigate neural circuitry on a fine scale, but for the rodent claustrum complex (CC) this has yet to be fully accomplished. The CC is generally considered to comprise two major subdivisions, the claustrum (CL) and the dorsal endopiriform nucleus (DEn), but regional boundaries to these areas...
Preprint
The general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projectio...
Preprint
Full-text available
The claustrum is highly interconnected with many structures in the brain, but the organizing principles governing its vast connectivity have yet to be fully explored. We investigated the defining characteristics and activity of single claustrum neurons, the nature of their relationship with the cortex, and their connectivity within the claustrum it...
Preprint
Full-text available
Reconstructing dense 3D anatomical coordinates from 2D projective measurements has become a central problem in digital pathology for both animal models and human studies. We describe a new family of diffeomorphic mapping technologies called Projective LDDMM which generate diffeomorphic mappings of dense human MRI atlases at tissue scales onto spars...
Article
Little is known about the development of the human entorhinal cortex (EC), a major hub in a widespread network for learning and memory, spatial navigation, high‐order processing of object information, multimodal integration, attention and awareness, emotion, motivation, and perception of time. We analyzed a series of 20 fetal and two adult human br...
Preprint
Full-text available
Since Braak's initial histological observations, it has been recognized that Alzheimer's disease (AD) neurofibrillary tangles (NFTs) appear in the medial temporal lobe (MTL) of the brain very early in the disease course. MRI-based shape diffeomorphometry markers have demonstrated preclinical AD changes in the MTL but it has not been possible to con...
Preprint
Full-text available
GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. GABAergic neurons show an extraordinary diversity in their morphology, physiology, molecular markers and connectivity. This diversity allows GABAergic neurons to participate in a wide variety of microc...
Preprint
Projection neurons in the anterolateral part of entorhinal cortex layer II (alEC LII) are the predominant cortical site for hyperphosphorylation of tau (p-tau) and formation of neurofibrillary tangles (NFTs) in brains of subjects with early-stage Alzheimer’s Disease (AD). A majority of alEC LII-neurons are unique among cortical excitatory neurons b...
Article
Full-text available
The entorhinal cortex (EC) is a major gateway between the hippocampus and telencephalic structures, and plays a critical role in memory and navigation. Through the use of various molecular markers and genetic tools, neuron types constituting EC are well studied in rodents, and their layer-dependent distributions, connections, and functions have als...
Article
Full-text available
The wide diversity of cortical inhibitory neuron types populating the cortex allows the assembly of diverse microcircuits and endows these circuits with different computational properties. Thus, characterizing neuronal diversity is fundamental to describe the building blocks of cortical microcircuits and probe their function. To this purpose, the m...
Article
Full-text available
The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but un...
Preprint
Full-text available
The wide diversity of cortical inhibitory neuron types populating the cortex allows the assembly of diverse microcircuits and endows these circuits with different computational properties. Thus, characterizing neuronal diversity is fundamental to describe the building blocks of cortical microcircuits and probe their function. To this purpose, the m...
Preprint
Full-text available
The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posterior-medial (pmEC) and anterior-lateral (alEC) parts,...
Article
Full-text available
The entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as w...
Article
Full-text available
CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions. However, how such information is encoded in CA1 and SUB and the resulting impact on downstr...
Article
Full-text available
The entorhinal cortex, in particular neurons in layer V, allegedly mediate transfer of information from the hippocampus to the neocortex, underlying long-term memory. Recently, this circuit has been shown to comprise a hippocampal output recipient layer Vb and a cortical projecting layer Va. With the use of in vitro electrophysiology in transgenic...
Preprint
Full-text available
The entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as w...
Article
Full-text available
The entorhinal-hippocampal system contains distinct networks subserving declarative memory. This system is selectively vulnerable to changes of ageing and pathological processes. The entorhinal cortex (EC) is a pivotal component of this memory system since it serves as the interface between the neocortex and the hippocampus. EC is heavily affected...
Article
Full-text available
The calcium-binding proteins parvalbumin and calbindin are expressed in neuronal populations regulating brain networks involved in spatial navigation, memory processes, and social interactions. Information about the numbers of these neurons across brain regions is required to understand their functional roles but is scarcely available. Employing se...
Chapter
The Stereotaxic Brain Atlas of the Egyptian Fruit Bat provides the first stereotaxic atlas of the Egyptian fruit bat (Rousettus aegyptiacus), an emerging model in neuroscience. This atlas contains coronal brain sections stained with cresyl violet (Nissl), AChE, and Parvalbumin—all stereotaxically calibrated, and annotated. Appendixes include sagitt...
Chapter
The Stereotaxic Brain Atlas of the Egyptian Fruit Bat provides the first stereotaxic atlas of the Egyptian fruit bat (Rousettus aegyptiacus), an emerging model in neuroscience. This atlas contains coronal brain sections stained with cresyl violet (Nissl), AChE, and Parvalbumin—all stereotaxically calibrated, and annotated. Appendixes include sagitt...
Article
Anatomical, electrophysiological and behavioral studies in rodents have shown that the thalamic midline nucleus reuniens (RE) is a crucial link in the communication between hippocampal formation (HIP, i.e., CA1, subiculum) and medial prefrontal cortex (mPFC), important structures for cognitive and executive functions. A common feature in neurodevel...
Article
Full-text available
In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to el...
Article
Full-text available
In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to el...
Preprint
The entorhinal cortex, in particular neurons in layer V, allegedly mediate transfer of information between the hippocampus and the neocortex, underlying long-term memory. Recently, this circuit has been shown to comprise a hippocampal output recipient layer Vb and a cortical projecting layer Va. With the use of in vitro electrophysiology in transge...
Article
Full-text available
Locomotion activates an array of sensory inputs that may help build the self-position map of the medial entorhinal cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations of the animal's position. A possible origin for the entorhinal speed signal is the mesencephalic locomotor region (MLR), which is critica...
Article
The organization of projections from the macaque monkey hippocampus, subiculum, presubiculum and parasubiculum to the entorhinal cortex was analyzed using anterograde and retrograde tracing techniques. Projections exclusively originate in the CA1 field of the hippocampus and in the subiculum, presubiculum and parasubiculum. The CA1 and subicular pr...
Preprint
Full-text available
CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions. However, how such information is encoded in CA1 and SUB, and the resulting impact on downst...
Article
Full-text available
One of the main subcortical targets of hippocampal formation efferents is the lateral septum. Previous studies on the subicular projections, as a main output structure of the hippocampus, have shown a clear topographic organization of septal innervation, related to the origin of the fibers along the dorsoventral axis of the subiculum in the adult b...
Article
Full-text available
In the present study we provide the first systematic and quantitative hodological study of the calbindin-expressing (CB+) principal neurons in layer II of the entorhinal cortex and compared the respective projections of the lateral and medial subdivisions of the entorhinal cortex. Using elaborate quantitative retrograde tracing, complemented by ant...
Article
Full-text available
Neurons in parasubiculum (PaS), presubiculum (PrS), and medial entorhinal cortex (MEC) code for place (grid cells) and head direction. Directional input has been shown to be important for stable grid cell properties in MEC, and PaS and PrS have been postulated to provide this information to MEC. In line with this, head direction cells in those brai...