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Cortex; a Journal Devoted To the Study... Feb 2022The cortical connections of the human hippocampal memory system are fundamental to understanding its operation in health and disease, especially in the context of the...
The cortical connections of the human hippocampal memory system are fundamental to understanding its operation in health and disease, especially in the context of the great development of the human cortex. The functional connectivity of the human hippocampal system was analyzed in 172 participants imaged at 7T in the Human Connectome Project. The human hippocampus has high functional connectivity not only with the entorhinal cortex, but also with areas that are more distant in the ventral 'what' stream including the perirhinal cortex and temporal cortical visual areas. Parahippocampal gyrus TF in humans has connectivity with this ventral 'what' subsystem. Correspondingly for the dorsal stream, the hippocampus has high functional connectivity not only with the presubiculum, but also with areas more distant, the medial parahippocampal cortex TH which includes the parahippocampal place or scene area, the posterior cingulate including retrosplenial cortex, and the parietal cortex. Further, there is considerable cross connectivity between the ventral and dorsal streams with the hippocampus. The findings are supported by anatomical connections, which together provide an unprecedented and quantitative overview of the extensive cortical connectivity of the human hippocampal system that goes beyond hierarchically organised and segregated pathways connecting the hippocampus and neocortex, and leads to new concepts on the operation of the hippocampal memory system in humans.
Topics: Entorhinal Cortex; Hippocampus; Humans; Neural Pathways; Parahippocampal Gyrus; Perirhinal Cortex; Temporal Lobe
PubMed: 35026557
DOI: 10.1016/j.cortex.2021.11.014 -
Neuroscience Aug 2022The amygdala, specifically its basolateral nucleus (BLA), is a critical site integrating neuromodulatory influences on memory consolidation in other brain areas. Almost... (Review)
Review
The amygdala, specifically its basolateral nucleus (BLA), is a critical site integrating neuromodulatory influences on memory consolidation in other brain areas. Almost 20 years ago, we reported the first direct evidence that BLA activity is required for modulatory interventions in the entorhinal cortex (EC) to affect memory consolidation (Roesler, Roozendaal, and McGaugh, 2002). Since then, significant advances have been made in our understanding of how the EC participates in memory. For example, the characterization of grid cells specialized in processing spatial information in the medial EC (mEC) that act as major relayers of information to the hippocampus (HIP) has changed our view of memory processing by the EC; and the development of optogenetic technologies for manipulation of neuronal activity has recently enabled important new discoveries on the role of the BLA projections to the EC in memory. Here, we review the current evidence on interactions between the BLA and EC in synaptic plasticity and memory formation. The findings suggest that the EC may function as a gateway and mediator of modulatory influences from the BLA, which are then processed and relayed to the HIP. Through extensive reciprocal connections among the EC, HIP, and several cortical areas, information related to new memories is then consolidated by these multiple brain systems, through various molecular and cellular mechanisms acting in a distributed and highly concerted manner, during several hours after learning. A special note is made on the contribution by Ivan Izquierdo to our understanding of memory consolidation at the brain system level.
Topics: Amygdala; Entorhinal Cortex; Learning; Memory; Memory Consolidation
PubMed: 35122874
DOI: 10.1016/j.neuroscience.2022.01.023 -
Progress in Neurobiology Jan 2023The amygdala and orbitofrontal cortex have been implicated in emotion. To understand these regions better in humans, their effective connectivity with 360 cortical...
The amygdala and orbitofrontal cortex have been implicated in emotion. To understand these regions better in humans, their effective connectivity with 360 cortical regions was measured in 171 humans from the Human Connectome Project, and complemented with functional connectivity and diffusion tractography. The human amygdala has effective connectivity from few cortical regions compared to the orbitofrontal cortex: primarily from auditory cortex A5 and the related superior temporal gyrus and temporal pole regions; the piriform (olfactory) cortex; the lateral orbitofrontal cortex 47m; somatosensory cortex; the hippocampus, entorhinal cortex, perirhinal cortex, and parahippocampal TF; and from the cholinergic nucleus basalis. The amygdala has effective connectivity to the hippocampus, entorhinal and perirhinal cortex; to the temporal pole; and to the lateral orbitofrontal cortex. The orbitofrontal cortex has effective connectivity from gustatory, olfactory, and temporal visual, auditory and pole cortex, and to the pregenual anterior and posterior cingulate cortex, hippocampal system, and prefrontal cortex, and provides for rewards and punishers to be used in reported emotions, and memory and navigation to goals. Given the paucity of amygdalo-neocortical connectivity in humans, it is proposed that the human amygdala is involved primarily in autonomic and conditioned responses via brainstem connectivity, rather than in reported (declarative) emotion.
Topics: Humans; Prefrontal Cortex; Amygdala; Hippocampus; Emotions; Entorhinal Cortex; Neural Pathways
PubMed: 36442728
DOI: 10.1016/j.pneurobio.2022.102385 -
Progress in Neurobiology Jun 2021The subiculum serves as the strategic core output of the hippocampus, through which neural activity exits the hippocampal proper and targets the entorhinal cortex and... (Review)
Review
The subiculum serves as the strategic core output of the hippocampus, through which neural activity exits the hippocampal proper and targets the entorhinal cortex and other more distant subcortical and cortical areas. The past decade has witnessed a growing interest in the subiculum, owing to discoveries revealing its critical role in regulating many physiological and pathophysiological processes. Notably, accumulating evidence from both clinical and experimental studies suggests that the subiculum plays a vital role in seizure initiation and propagation, in epilepsy. In this review, we briefly describe the structure and connectivity of the subiculum and then summarize the molecular and cellular mechanisms in the subiculum underlying the epileptic brain, in both epilepsy patients and animal models. Next, we review some translational approaches targeting the malfunctioned subiculum to treat epilepsy. Finally, we pose open questions for future research in the subiculum and their clinical translation challenges.
Topics: Animals; Brain; Entorhinal Cortex; Epilepsy; Hippocampus; Humans; Seizures
PubMed: 33636224
DOI: 10.1016/j.pneurobio.2021.102029 -
ENeuro 2021We propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm; slow, middle, and fast gamma rhythms; and ripple oscillations. We have based this on...
We propose a model of the main rhythms in the hippocampal CA1 field: theta rhythm; slow, middle, and fast gamma rhythms; and ripple oscillations. We have based this on data obtained from animals behaving freely. We have considered the modes of neuronal discharges and the occurrence of local field potential oscillations in the theta and non-theta states at different inputs from the CA3 field, the medial entorhinal cortex, and the medial septum. In our work, we tried to reproduce the main experimental phenomena about rhythms in the CA1 field: the coupling of neurons to the phase of rhythms, cross-rhythm phase-phase coupling, and phase-amplitude coupling. Using computational experiments, we have proved the hypothesis that the descending phase of the theta rhythm in the CA1 field is formed by the input from the CA3 field via the Shaffer collaterals, and the ascending phase of the theta rhythm is formed by the IPSPs from CCK basket cells. The slow gamma rhythm is coupled to the descending phase of the theta rhythm, since it also depends on the arrival of the signal via the Shaffer collaterals. The middle gamma rhythm is formed by the EPSPs of the principal neurons of the third layer of the entorhinal cortex, corresponds to experimental data. We were able to unite in a single mathematical model several theoretical ideas about the mechanisms of rhythmic processes in the CA1 field of the hippocampus.
Topics: Animals; CA1 Region, Hippocampal; Entorhinal Cortex; Gamma Rhythm; Hippocampus; Theta Rhythm
PubMed: 34670820
DOI: 10.1523/ENEURO.0192-21.2021 -
Epilepsia Feb 2024To confirm and investigate why pathological high-frequency oscillations (pHFOs), including ripples (80-200 Hz) and fast ripples (200-600 Hz), are generated during...
OBJECTIVE
To confirm and investigate why pathological high-frequency oscillations (pHFOs), including ripples (80-200 Hz) and fast ripples (200-600 Hz), are generated during the UP-DOWN transition of the slow wave and if information transmission mediated by ripple temporal coupling is disrupted in the seizure-onset zone (SOZ).
METHODS
We isolated 217 total units from 175.95 intracranial electroencephalography (iEEG) contact-hours of synchronized macro- and microelectrode recordings from 6 patients. Sleep slow oscillation (.1-2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the SOZ, HFOs and associated action potentials (APs) occur more often at the UP-DOWN transition. We also examined ripple temporal correlations using cross-correlograms.
RESULTS
At the group level in the SOZ, HFO and HFO-associated AP probability was highest during the UP-DOWN transition of slow wave excitability (p < < .001). In the non-SOZ, HFO and HFO-associated AP was highest during the DOWN-UP transition (p < < .001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d = .11-.83) and fast ripples (d = .36-.90) at the UP-DOWN transition (p < .05 f.d.r. corrected), respectively. By comparison, also in the SOZ, 6.6% (d = .14-.30) and 8.5% (d = .33-.41) of units had significantly less firing during ripples and fast ripples at the UP-DOWN transition, respectively. Additional data shows that ripple and fast ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by >50% in the SOZ compared to the non-SOZ (N = 3).
SIGNIFICANCE
The UP-DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. Ripple temporal correlations across brain regions may be important in memory consolidation and are disrupted in the SOZ, perhaps by pHFO generation.
Topics: Humans; Electrocorticography; Brain; Sleep; Brain Waves; Parahippocampal Gyrus; Electroencephalography
PubMed: 38041560
DOI: 10.1111/epi.17845 -
NeuroImage Nov 2023The connectivity of the hippocampus is essential to its functions. To gain a whole system view of intrahippocampal connectivity, ex vivo mesoscale (100 μm isotropic...
The connectivity of the hippocampus is essential to its functions. To gain a whole system view of intrahippocampal connectivity, ex vivo mesoscale (100 μm isotropic resolution) multi-shell diffusion MRI (11.7T) and tractography were performed on entire post-mortem human right hippocampi. Volumetric measurements indicated that the head region was largest followed by the body and tail regions. A unique anatomical organization in the head region reflected a complex organization of the granule cell layer (GCL) of the dentate gyrus. Tractography revealed the volumetric distribution of the perforant path, including both the tri-synaptic and temporoammonic pathways, as well as other well-established canonical connections, such as Schaffer collaterals. Visualization of the perforant path provided a means to verify the borders between the pro-subiculum and CA1, as well as between CA1/CA2. A specific angularity of different layers of fibers in the alveus was evident across the whole sample and allowed a separation of afferent and efferent connections based on their origin (i.e. entorhinal cortex) or destination (i.e. fimbria) using a cluster analysis of streamlines. Non-canonical translamellar connections running along the anterior-posterior axis were also discerned in the hilus. In line with "dentations" of the GCL, mossy fibers were bunching together in the sagittal plane revealing a unique lamellar organization and connections between these. In the head region, mossy fibers projected to the origin of the fimbria, which was distinct from the body and tail region. Mesoscale tractography provides an unprecedented systems view of intrahippocampal connections that underpin cognitive and emotional processing.
Topics: Humans; Hippocampus; Perforant Pathway; Entorhinal Cortex; Brain; Diffusion Magnetic Resonance Imaging
PubMed: 37827206
DOI: 10.1016/j.neuroimage.2023.120406 -
Hippocampus Dec 2019Episodic memory is defined as the ability to recall events in a spatiotemporal context. Formation of such memories is critically dependent on the hippocampal formation... (Review)
Review
Episodic memory is defined as the ability to recall events in a spatiotemporal context. Formation of such memories is critically dependent on the hippocampal formation and its inputs from the entorhinal cortex. To be able to support the formation of episodic memories, entorhinal cortex and hippocampal formation should contain a neuronal code that follows several requirements. First, the code should include information about position of the agent ("where"), sequence of events ("when"), and the content of the experience itself ("what"). Second, the code should arise instantly thereby being able to support memory formation of one-shot experiences. For successful encoding and to avoid interference between memories during recall, variations in location, time, or in content of experience should result in unique ensemble activity. Finally, the code should capture several different resolutions of experience so that the necessary details relevant for future memory-based predictions will be stored. We review how neuronal codes in entorhinal cortex and hippocampus follow these requirements and argue that during formation of episodic memories entorhinal cortex provides hippocampus with instant information about ongoing experience. Such information originates from (a) spatially modulated neurons in medial entorhinal cortex, including grid cells, which provide a stable and universal positional metric of the environment; (b) a continuously varying signal in lateral entorhinal cortex providing a code for the temporal progression of events; and (c) entorhinal neurons coding the content of experiences exemplified by object-coding and odor-selective neurons. During formation of episodic memories, information from these systems are thought to be encoded as unique sequential ensemble activity in hippocampus, thereby encoding associations between the content of an event and its spatial and temporal contexts. Upon exposure to parts of the encoded stimuli, activity in these ensembles can be reinstated, leading to reactivation of the encoded activity pattern and memory recollection.
Topics: Animals; Entorhinal Cortex; Hippocampus; Humans; Memory, Episodic; Neurons; Neurosciences; Place Cells
PubMed: 31334573
DOI: 10.1002/hipo.23132 -
Neuroscience Jan 2020Clinical evidence and pathological studies suggest a bidirectional link between temporal lobe epilepsy and Alzheimer's disease (AD). Data analysis from omic studies...
Clinical evidence and pathological studies suggest a bidirectional link between temporal lobe epilepsy and Alzheimer's disease (AD). Data analysis from omic studies offers an excellent opportunity to identify the overlap in molecular alterations between the two pathologies. We have subjected proteomic data sets from a rat model of epileptogenesis to a bioinformatics analysis focused on proteins functionally linked with AD. The data sets have been obtained for hippocampus (HC) and parahippocampal cortex samples collected during the course of epileptogenesis. Our study confirmed a relevant dysregulation of proteins linked with Alzheimer pathogenesis. When comparing the two brain areas, a more prominent regulation was evident in parahippocampal cortex samples as compared to the HC. Dysregulated protein groups comprised those affecting mitochondrial function and calcium homeostasis. Differentially expressed mitochondrial proteins included proteins of the mitochondrial complexes I, III, IV, and V as well as of the accessory subunit of complex I. The analysis also revealed a regulation of the microtubule associated protein Tau in parahippocampal cortex tissue during the latency phase. This was further confirmed by immunohistochemistry. Moreover, we demonstrated a complex epileptogenesis-associated dysregulation of proteins involved in amyloid β processing and its regulation. Among others, the amyloid precursor protein and the α-secretase alpha disintegrin metalloproteinase 17 were included. Our analysis revealed a relevant regulation of key proteins known to be associated with AD pathogenesis. The analysis provides a comprehensive overview of shared molecular alterations characterizing epilepsy development and manifestation as well as AD development and progression.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Epilepsy; Female; Hippocampus; Mitochondrial Proteins; Parahippocampal Gyrus; Proteomics; Rats; Rats, Sprague-Dawley
PubMed: 31705965
DOI: 10.1016/j.neuroscience.2019.08.037 -
Brain Structure & Function May 2022Brain areas at the parahippocampal gyrus of the temporal-occipital transition region are involved in different functions including processing visual-spatial information...
Brain areas at the parahippocampal gyrus of the temporal-occipital transition region are involved in different functions including processing visual-spatial information and episodic memory. Results of neuroimaging experiments have revealed a differentiated functional parcellation of this region, but its microstructural correlates are less well understood. Here we provide probability maps of four new cytoarchitectonic areas, Ph1, Ph2, Ph3 and CoS1 at the parahippocampal gyrus and collateral sulcus. Areas have been identified based on an observer-independent mapping of serial, cell-body stained histological sections of ten human postmortem brains. They have been registered to two standard reference spaces, and superimposed to capture intersubject variability. The comparison of the maps with functional imaging data illustrates the different involvement of the new areas in a variety of functions. Maps are available as part of Julich-Brain atlas and can be used as anatomical references for future studies to better understand relationships between structure and function of the caudal parahippocampal cortex.
Topics: Brain Mapping; Humans; Neuroimaging; Neurons; Occipital Lobe; Parahippocampal Gyrus; Temporal Lobe
PubMed: 34989871
DOI: 10.1007/s00429-021-02441-2