HippocampusPub Date : 2024-10-15DOI: 10.1002/hipo.23644
Shane M. Ohline, Barbara J. Logan, Stephanie M. Hughes, Wickliffe C. Abraham
{"title":"Egr1 Expression Is Correlated With Synaptic Activity but Not Intrinsic Membrane Properties in Mouse Adult-Born Dentate Granule Cells","authors":"Shane M. Ohline, Barbara J. Logan, Stephanie M. Hughes, Wickliffe C. Abraham","doi":"10.1002/hipo.23644","DOIUrl":"10.1002/hipo.23644","url":null,"abstract":"<p>The discovery of adult-born granule cells (aDGCs) in the dentate gyrus of the hippocampus has raised questions regarding how they develop, incorporate into the hippocampal circuitry, and contribute to learning and memory. Here, we used patch-clamp electrophysiology to investigate the intrinsic and synaptic excitability of mouse aDGCs as they matured, enabled by using a tamoxifen-induced genetic label to birth date the aDGCs at different animal ages. Importantly, we also undertook immunofluorescence studies of the expression of the immediate early gene Egr1 and compared these findings with the electrophysiology data in the same animals. We examined two groups of animals, with aDGC birthdating when the mice were 2 months and at 7–9 months of age. In both groups, cells 4 weeks old had lower thresholds for current-evoked action potentials than older cells but fired fewer spikes during long current pulses and responded more poorly to synaptic activation. aDGCs born in both 2 and 7–9-month-old mice matured in their intrinsic excitability and synaptic properties from 4–12 weeks postgenesis, but this occurred more slowly for the older age animals. Interestingly, this pattern of intrinsic excitability changes did not correlate with the pattern of Egr1 expression. Instead, the development of Egr1 expression was correlated with the frequency of spontaneous excitatory postsynaptic currents. These results suggest that in order for aDGCs to fully participate in hippocampal circuitry, as indicated by Egr1 expression, they must have developed enough synaptic input, in spite of the greater input resistance and reduced firing threshold that characterizes young aDGCs.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 12","pages":"729-743"},"PeriodicalIF":2.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-10-07DOI: 10.1002/hipo.23643
Mumeko C. Tsuda, Talia Akoh-Arrey, Jeffrey C. Mercurio, Ariana Rucker, Megan L. Airey, Hannah Jacobs, Daria Lukasz, Lijing Wang, Heather A. Cameron
{"title":"Adult Neurogenesis and the Initiation of Social Aggression in Male Mice","authors":"Mumeko C. Tsuda, Talia Akoh-Arrey, Jeffrey C. Mercurio, Ariana Rucker, Megan L. Airey, Hannah Jacobs, Daria Lukasz, Lijing Wang, Heather A. Cameron","doi":"10.1002/hipo.23643","DOIUrl":"10.1002/hipo.23643","url":null,"abstract":"<p>The hippocampus is important for social behavior and exhibits unusual structural plasticity in the form of continued production of new granule neurons throughout adulthood, but it is unclear how adult neurogenesis contributes to social interactions. In the present study, we suppressed neurogenesis using a pharmacogenetic mouse model and examined social investigation and aggression in adult male mice to investigate the role of hippocampal adult-born neurons in the expression of aggressive behavior. In simultaneous choice tests with stimulus mice placed in corrals, mice with complete suppression of adult neurogenesis in adulthood (TK mice) exhibited normal social investigation behaviors, indicating that new neurons are not required for social interest, social memory, or detection of and response to social olfactory signals. However, mice with suppressed neurogenesis displayed decreased offensive and defensive aggression in a resident-intruder paradigm, and less resistance in a social dominance test, relative to neurogenesis-intact controls, when paired with weight and strain-matched (CD-1) mice. During aggression tests, TK mice were frequently attacked by the CD-1 intruder mice, which never occurred with WTs, and normal CD-1 male mice investigated TK mice less than controls when corralled in the social investigation test. Importantly, TK mice showed normal aggression toward prey (crickets) and smaller, nonaggressive (olfactory bulbectomized) C57BL/6J intruders, suggesting that mice lacking adult neurogenesis do not avoid aggressive social interactions if they are much larger than their opponent and will clearly win. Taken together, our findings show that adult hippocampal neurogenesis plays an important role in the instigation of intermale aggression, possibly by weighting a cost–benefit analysis against confrontation in cases where the outcome of the fight is not clear.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 12","pages":"711-728"},"PeriodicalIF":2.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-10-07DOI: 10.1002/hipo.23642
Christopher Hagen, Megi Hoxha, Saee Chitale, Andre O. White, Pedro M. Ogallar, Alejandro N. Expósito, Antonio D. R. Agüera, Carmen Torres, Mauricio R. Papini, Marta Sabariego
{"title":"Flexible Behavioral Adjustment to Frustrative Nonreward in Anticipatory Behavior, but Not in Consummatory Behavior, Requires the Dorsal Hippocampus","authors":"Christopher Hagen, Megi Hoxha, Saee Chitale, Andre O. White, Pedro M. Ogallar, Alejandro N. Expósito, Antonio D. R. Agüera, Carmen Torres, Mauricio R. Papini, Marta Sabariego","doi":"10.1002/hipo.23642","DOIUrl":"10.1002/hipo.23642","url":null,"abstract":"<div>\u0000 \u0000 <p>The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3–5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 12","pages":"688-710"},"PeriodicalIF":2.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-10-05DOI: 10.1002/hipo.23641
Aditi Bishnoi, Sachin S. Deshmukh
{"title":"Comparable Theta Phase Coding Dynamics Along the Transverse Axis of CA1","authors":"Aditi Bishnoi, Sachin S. Deshmukh","doi":"10.1002/hipo.23641","DOIUrl":"10.1002/hipo.23641","url":null,"abstract":"<div>\u0000 \u0000 <p>Topographical projection patterns from the entorhinal cortex to area CA1 of the hippocampus have led to a hypothesis that proximal CA1 (pCA1, closer to CA2) is spatially more selective than distal CA1 (dCA1, closer to the subiculum). While earlier studies have shown evidence supporting this hypothesis, we recently showed that this difference does not hold true under all experimental conditions. In a complex environment with distinct local texture cues on a circular track and global visual cues, pCA1 and dCA1 display comparable spatial selectivity. Correlated with the spatial selectivity differences, the earlier studies also showed differences in theta phase coding dynamics between pCA1 and dCA1 neurons. Here we show that there are no differences in theta phase coding dynamics between neurons in these two regions under the experimental conditions where pCA1 and dCA1 neurons are equally spatially selective. These findings challenge the established notion of dCA1 being inherently less spatially selective and theta modulated than pCA1 and suggest further experiments to understand theta-mediated activation of the CA1 sub-networks to represent space.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 12","pages":"674-687"},"PeriodicalIF":2.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-09-21DOI: 10.1002/hipo.23639
Ingrid Framås Syversen, Daniel Reznik, Menno P. Witter, Asgeir Kobro-Flatmoen, Tobias Navarro Schröder, Christian F. Doeller
{"title":"A combined DTI-fMRI approach for optimizing the delineation of posteromedial versus anterolateral entorhinal cortex","authors":"Ingrid Framås Syversen, Daniel Reznik, Menno P. Witter, Asgeir Kobro-Flatmoen, Tobias Navarro Schröder, Christian F. Doeller","doi":"10.1002/hipo.23639","DOIUrl":"10.1002/hipo.23639","url":null,"abstract":"<p>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 seed regions and the imaging modality used. While DTI can be used to follow the white matter tracts of the brain, fMRI can identify functionally connected brain regions. In this study, we used both DTI and resting-state fMRI in 103 healthy adults to investigate both structural and functional connectivity between the EC and associated cortical brain regions. Differential connectivity with these regions was then used to predict the locations of the human homologues of MEC and LEC. Our results from combining DTI and fMRI support a subdivision into posteromedial (pmEC) and anterolateral (alEC) EC and reveal a confined border between the pmEC and alEC. Furthermore, the EC subregions obtained by either imaging modality showed similar distinct whole-brain connectivity profiles. Optimizing the delineation of the human homologues of MEC and LEC with a combined, cross-validated DTI-fMRI approach allows to define a likely border between the two subdivisions and has implications for both cognitive and translational neuroscience research.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 11","pages":"659-672"},"PeriodicalIF":2.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-09-18DOI: 10.1002/hipo.23640
Maria Jieun Hwang, Sang Ah Lee
{"title":"Cover Image, Volume 34, Issue 10","authors":"Maria Jieun Hwang, Sang Ah Lee","doi":"10.1002/hipo.23640","DOIUrl":"https://doi.org/10.1002/hipo.23640","url":null,"abstract":"<p>The cover image is based on the article <i>Scene construction processes in the anterior hippocampus during temporal episodic memory retrieval</i> by Maria Jieun Hwang and Sang Ah Lee (https://doi.org/10.1002/hipo.23624).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 10","pages":"C1"},"PeriodicalIF":2.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-09-13DOI: 10.1002/hipo.23634
Matthew Napier, Ashish Kumar, Natasha Szulist, Dale Martin, Angela L. Scott
{"title":"P2X7 expression patterns in the developing Fmr1-knockout mouse hippocampus","authors":"Matthew Napier, Ashish Kumar, Natasha Szulist, Dale Martin, Angela L. Scott","doi":"10.1002/hipo.23634","DOIUrl":"10.1002/hipo.23634","url":null,"abstract":"<p>Fragile-X Syndrome (FXS) is the leading monogenetic cause of intellectual disability among children but remains without a cure. Using the <i>Fmr1</i> <i>KO</i> mouse model of FXS, much work has been done to understand FXS hippocampus dysfunction. Purinergic signaling, where ATP and its metabolites are used as signaling molecules, participates in hippocampus development, but it is unknown if purinergic signaling is affected in the developing <i>Fmr1</i> <i>KO</i> hippocampus. In our study, we characterized the purinergic receptor P2X7. We first found that P2X7 was reduced in <i>Fmr1 KO</i> whole hippocampus tissue at P14 and P21, corresponding to the periods of neurite outgrowth and synaptic refinement in the hippocampus. We then evaluated the cell-specific expression of P2X7 with immunofluorescence and found differences between WT and <i>Fmr1 KO</i> mice in P2X7 colocalization with hippocampal microglia and neurons. P2X7 colocalized more with microglia at P14 and P21, but there was a sex-specific reduction in P2X7 colocalization with neurons. In contrast, male mice at P14 and P21 showed reduced neuronal P2X7 colocalization compared to females, but only females showed reduced absolute neuronal P2X7 expression across the dorsal hippocampal formation. Together, our results suggest that P2X7 expression is altered during <i>Fmr1</i>-KO hippocampal development, potentially influencing several developmental processes in the <i>Fmr1-</i>KO hippocampus formation.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 11","pages":"633-644"},"PeriodicalIF":2.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23634","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-09-13DOI: 10.1002/hipo.23638
Loïc J. Chareyron, W. K. Kling Chong, Tina Banks, Neil Burgess, Richard C. Saunders, Faraneh Vargha-Khadem
{"title":"Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations","authors":"Loïc J. Chareyron, W. K. Kling Chong, Tina Banks, Neil Burgess, Richard C. Saunders, Faraneh Vargha-Khadem","doi":"10.1002/hipo.23638","DOIUrl":"10.1002/hipo.23638","url":null,"abstract":"<p>Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (−24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 11","pages":"645-658"},"PeriodicalIF":2.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HippocampusPub Date : 2024-09-11DOI: 10.1002/hipo.23637
Devon James Hupka, Andrew Abey, Ehsan Misaghi, Justine Gargula, Trevor Adam Steve
{"title":"Curved multiplanar reformatting allows the accurate histological delineation of hippocampal subfields","authors":"Devon James Hupka, Andrew Abey, Ehsan Misaghi, Justine Gargula, Trevor Adam Steve","doi":"10.1002/hipo.23637","DOIUrl":"10.1002/hipo.23637","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hippocampal subfields perform specific roles in normal cognitive functioning and have distinct vulnerabilities in neurological disorders. However, measurement of subfields with MRI is technically difficult in the head and tail of the hippocampus. Recent studies have utilized curved multiplanar reconstruction (CMPR) to improve subfield visualization in the head and tail, but this method has not yet been applied to histological data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized BigBrain data, an open-source database of serially sectioned histological data for our analyses. The left hippocampus was segmented according to histological criteria by two raters in order to evaluate intra- and inter-rater reliability of histology-based segmentation throughout the long axis. Segmentation according to our previous protocol for the hippocampal body was then compared to these histological measurements to evaluate for histological validity. Agreement between segmentations was evaluated using Dice similarity coefficients (DSCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intra-rater reliability (DSCs) of histological segmentation was excellent for all subfields: CA1 (0.8599), CA2 (0.7586), CA3/CA4/DG (0.8907), SLM (0.9123), subiculum (0.8149). Similarly, inter-rater reliability analysis demonstrated excellent agreement (DSCs) for all subfield locations: CA1 (0.8203), CA2 (0.7253), CA3/CA4/DG (0.8439), SLM (0.8700), subiculum (0.7794). Finally, histological accuracy (DSCs) for our previous protocol was excellent for all subfields: CA1 (0.8821), CA2 (0.8810), CA3/CA4/DG (0.9802), SLM (0.9879), subiculum (0.8774). When subfields in the hippocampus head, body, and tail were analyzed independently, DSCs also showed excellent agreement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMPR allows reliable subfield segmentation based on histological criteria throughout the hippocampal head, body, and tail. Our previous protocol for the hippocampal body can be applied to provide histologically valid subfield measurements throughout the entire hippocampal long axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"34 11","pages":"625-632"},"PeriodicalIF":2.4,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.23637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142203809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}