Firing Patterns of Ventral Hippocampal Neurons Predict the Exploration of Anxiogenic Locations

Malagon‐Vina, Hugo; Ciocchi, Stéphane; Klausberger, Thomas

doi:10.2139/ssrn.4086942

Cited by 3 publications

(8 citation statements)

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“…On average, dHPC neurons were inhibited during freezing events while vHPC neurons were not ( Figure 2A-B ). This result failed to support our initial hypothesis, and was surprising given the ample published evidence for a role of vHPC in controlling anxiety and fear behavior 13,20,22,24,37 . A possible explanation for the dHPC freezing-associated inhibition would be related to the motor, rather than the emotional, aspects of freezing.…”

Section: Resultscontrasting

confidence: 81%

“…First, the precision of spatial coding diminishes along the dorsoventral axis of the HPC [15][16][17][18] . Second, neurons in more ventral parts of the HPC exhibit a stronger association with the emotional valence of locations [19][20][21][22] and odors 23 as compared to the dHPC. Moreover, recent work further suggests that specific pathways between the vHPC, the amygdala, and the prefrontal cortex are key for anxiety and fear-related behaviors 13,20,[24][25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

“…This result failed to support our initial hypothesis, and was surprising given the ample published evidence for a role of vHPC in controlling anxiety and fear behavior. 12, 14, 16, 17, 22 A possible explanation for the dHPC freezing-associated inhibition would be related to the motor, rather than the emotional, aspects of freezing. Previous work had shown that activity in dHPC is modulated more by animals’ speed than vHPC.…”

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confidence: 99%

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Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Pompili,

Hamou,

Wiener

2024

Preprint

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While there is substantial evidence that the dorsal and ventral hippocampus play different roles during emotional learning, it is unknown how these roles are implemented. Here, we simultaneously recorded in these structures during fear conditioning, and demonstrated a predominance of responses related to fear expression in dorsal hippocampus, while ventral hippocampal responses were more closely linked with the acquisition of conditioned fear. Furthermore, cell assemblies containing both dorsal and ventral neurons emerged during fear conditioning, therefore suggesting a potential substrate to integrate these complementary signals for learning and behavior.

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Section: Resultscontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Pompili,

Hamou,

Wiener

2024

Preprint

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“…A home-made adjustable linear track maze (31) (L80 cm x W10-7 cm x H12 cm) was built in order to create 4 different anxiety levels in mice: First, a ‘no anxiety’ (NA, Figure 1A top left) configuration in which the entire maze was surrounded by walls and the mice had to visual insight into the height of the maze. Second, a ‘low anxiety’ (LA, Figure 1A top right) configuration in which the openable second half of the maze was opened and the mice could perceive the 70 cm height of the maze.…”

Section: Methodsmentioning

confidence: 99%

“…A home-made adjustable linear track maze (31) (L80 cm x W10-7 cm x H12 cm, Suppl. video 1) was built in order to create 6 different anxiety levels in mice: 1. a ‘no anxiety’ (NA, Figure 1A top left) configuration in which the entire maze was surrounded by walls and the mice had no visual insight into the height of the maze.…”

Section: Methodsmentioning

confidence: 99%

Scaling of ventral hippocampal activity during anxiety

Cerquetella,

Gontier,

Forro

et al. 2023

Preprint

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BackgroundThe hippocampus supports a multiplicity of functions, with the dorsal region contributing to memory-related spatial representations, while the ventral hippocampus (vH) is primarily involved in emotional processing. While spatial encoding has been extensively investigated, how the vH activity is tuned to emotional states, e.g. to different anxiety levels, is not well understood.MethodsWe developed an adjustable linear track maze (aLTM) for mice to induce different anxiety levels within the same spatial environment. Throughin vivosingle-unit recordings, optogenetic manipulations, and the application of a convolutional classifier, we examined the changes and causal effects of vH activity at different anxiety levels.ResultsWe found that anxiogenic experiences activated the vH and that this activity scaled with increasing anxiety levels within the same spatial environment. We identified two processes that contributed to this scaling of anxiety-related activity: rate remapping and the successive recruitment of neurons. Moreover, optogenetic inhibition of the vH reduced anxiety across different levels, while anxiety-related activity scaling could be decoded using a convolutional classifier.ConclusionsOur findings position the vH as a critical limbic region that functions as an ‘anxiometer’ by scaling its activity based on perceived anxiety levels. Our discoveries go beyond the traditional theory of cognitive maps in the hippocampus underlying spatial navigation and memory, by identifying hippocampal mechanisms selectively regulating anxiety.

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Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin-1 Suppression in Female Mice with Increased Anxiety-Like Behaviors

Zeng,

Zhang,

Shen

et al. 2024

Neuroendocrinology

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Introduction: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. Methods: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor β (ERβ) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. Results: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and proinflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERβ partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. Conclusions: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice.

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Firing Patterns of Ventral Hippocampal Neurons Predict the Exploration of Anxiogenic Locations

Cited by 3 publications

References 62 publications

Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Differential encoding of fear learning and fear expression in the ventral and dorsal hippocampus

Scaling of ventral hippocampal activity during anxiety

Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin-1 Suppression in Female Mice with Increased Anxiety-Like Behaviors

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