Automated detection of c-Fos-expressing neurons using inhomogeneous background subtraction in fluorescent images

Neurobiology of Learning and Memory, Journal Year: 2025, Volume and Issue: 218, P. 108035 - 108035

Published: Feb. 20, 2025

Language: Английский

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Systems consolidation induces multiple memory engrams for a flexible recall strategy in observational fear memory in male mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 5, 2023

Abstract Observers learn to fear the context in which they witnessed a demonstrator’s aversive experience, called observational contextual conditioning (CFC). The neural mechanisms governing whether recall of CFC memory occurs from observer’s own or point view remain unclear. Here, we show male mice that recent is recalled only, but remote both observer and demonstrator contexts. Recall requires dorsal hippocampus activity, while contexts medial prefrontal cortex (mPFC)-basolateral amygdala pathway. Although mPFC neurons activated by are involved contexts, distinct subpopulations regulate each context. Our data provide insights into flexible strategy functional reorganization circuits engram cells underlying memory.

Language: Английский

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Paradoxical Boosting of Weak and Strong Spatial Memories by Hippocampal Dopamine Uncaging

eNeuro, Journal Year: 2024, Volume and Issue: 11(5), P. ENEURO.0469 - 23.2024

Published: May 1, 2024

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release hippocampal CA1 region could modulate spatial memory formation. However, role of increase on weak or strong memories remains unclear. We show male mice exploring two objects located a familiar environment 5 min created short-term (weak) cannot be retrieved 1 d later, whereas 10 exploration long-term (strong) can later. Remarkably, elevation during encoding object location (OLMs) allowed their retrieval later but OLMs promoted preference over after 24 h. Moreover, uncaging did not have effect diminished location. Additionally, allow recovery and affect traces. Finally, increased theta oscillations, indicating promotes recurrent activation specific groups neurons. Our experiments demonstrate dopaminergic modulation depends strength hyperdopaminergic levels enhance experiences compromise normal storage memories.

Language: Английский

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Postsynaptic histamine H3 receptors in ventral basal forebrain cholinergic neurons modulate contextual fear memory

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113073 - 113073

Published: Sept. 1, 2023

Overly strong fear memories can cause pathological conditions. Histamine H3 receptor (H3R) has been viewed as an optimal drug target for CNS disorders, but its role in memory remains elusive. We find that a selective deficit of H3R cholinergic neurons, not glutamatergic enhances freezing level during contextual retrieval without affecting cued memory. Consistently, genetically knocking down or chemogenetically activating neurons the ventral basal forebrain (vBF) mimics this enhanced memory, whereas augmentation is rescued by re-expressing chemogenetic inhibition vBF neurons. Spatiotemporal regulation light-sensitive rhodopsin-H3R fusion protein suggests postsynaptic H3Rs presynaptic projections dorsal hippocampus, are responsible modulating Therefore, precise modulation cell-type- and subcellular-location-specific manner should be explored

Language: Английский

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Reactivation of memory-associated neurons induces downstream suppression of competing neuronal populations

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(14)

Published: April 1, 2025

Inducing apparent memory recall by tagging and optogenetically reactivating cells in the hippocampus was demonstrated over a decade ago. However, hippocampal dynamics resulting from this reactivation remain largely unknown. While calcium imaging is commonly used as measure of neuronal activity, GCaMP, most common indicator, cannot be with optogenetic because both require blue light excitation. To resolve overlap, we demonstrate red-shifted opsin, ChrimsonR. We then conduct dual-color CA1 during DG. In addition to measuring population CA1, tagged original experience were identified. fear-conditioned animals (FC+), nontagged decreased their firing rate stimulation, while maintained activity level. FC+ animals, behavioral effect stimulation across days, so did changes neural stimulation. Our results technical feasibility memory-associated neurons advance our understanding underlying reactivation.

Language: Английский

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Combinative protein expression of immediate early genes c-Fos, Arc, and Npas4 along aversive- and reward-related neural networks

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract Expression of immediate early genes (IEGs) is critical for memory formation and has been widely used to identify the neural substrate traces, termed engram cells. However, types IEG have relatively not distinguished in identifying cells, as there limited knowledge about extent which different IEGs are selectively or concurrently involved engram. To address this question, we investigated combinative expression c-Fos, Arc, Npas4 proteins using immunohistochemistry following aversive rewarding experiences across subregions prefrontal cortex (PFC), basolateral amygdala (BLA), hippocampal dentate gyrus (DG), retrosplenial (RSC). Using an automated cell detection algorithm, found that patterns Npas4, Arc varied brain areas, with a higher increase expressing cells PFC posterior BLA than DG. The patterns, along their learning-induced changes, also differed areas; co-expression increased learning whereas was less pronounced DG RSC. Furthermore, demonstrate area-to-area functional connectivity networks were extracted by IEGs. These findings provide insights into how combinations will contribute deeper understanding significance IEG-tagged

Language: Английский

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

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 166(2), P. 172 - 188

Published: May 30, 2023

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

Language: Английский

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Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 1, 2023

Behavioral pattern separation and cognitive flexibility are essential abilities that disrupted in many brain disorders. A better understanding of the neural circuitry involved these will open paths to treatment. In humans mice, discrimination adaptation rely on integrity hippocampal dentate gyrus (DG) which receives glutamatergic input from entorhinal cortex (EC), including lateral EC (LEC). An inducible increase EC-DG circuit activity improves simple hippocampal-dependent associative learning increases DG neurogenesis. Here, we asked if LEC fan cells directly project (LEC → neurons) regulates relatively more complex behavioral or flexibility. C57BL/6J male mice received bilateral infusions a virus expressing shRNA TRIP8b, an auxiliary protein HCN channel control (SCR shRNA). Prior work shows 4 weeks post-surgery, TRIP8b have neurogenesis greater neurons compared SCR mice. underwent testing for reversal (touchscreen-based location [LDR]) innate fear spaces (elevated plus maze [EPM]) followed by quantification new (doublecortin-immunoreactive [DCX+] cells). There was no effect treatment vs. TRIP8b) performance during general touchscreen training, LDR 1st days testing. However, last testing, had improved (reached first quickly accurate discrimination) specifically when load high (lit squares close together “small separation”). The were also cognitively flexible (achieved reversals) Supporting specific influence behavior, did not differ total distance traveled time spent closed arms EPM. LEC-DG activity, increased. These data indicate This study advances fundamental translational neuroscience knowledge relevant two functions critical survival—behavioral flexibility—and suggests merits exploration as therapeutic target normalize dysfunctional output.

Language: Английский

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Understanding Others’ Distress Through Past Experiences: The Role of Memory Engram Cells in Observational Fear

Advances in neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 215 - 234

Published: Jan. 1, 2024

Language: Английский

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Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 27, 2023

Behavioral pattern separation and cognitive flexibility are essential abilities which disrupted in many brain disorders. Better understanding of the neural circuitry involved these will open paths to treatment. In humans mice, discrimination adaptation rely on integrity hippocampal dentate gyrus (DG) both receive glutamatergic input from entorhinal cortex (EC), including lateral EC (LEC). Inducible increase EC-DG circuit activity improves simple hippocampal-dependent associative learning increases DG neurogenesis. Here we asked if LEC fan cells that directly project (LEC➔DG neurons) regulates behavioral or flexibility. C57BL6/J male mice received bilateral infusions a virus expressing shRNA TRIP8b, an auxiliary protein HCN channel control (SCR shRNA); this approach LEC➔DG neurons. Four weeks later, underwent testing for reversal (touchscreen-based Location Discrimination Reversal [LDR] task) innate fear spaces (elevated plus maze [EPM]) followed by counting new neurons (doublecortin-immunoreactive [DCX+] cells). TRIP8b SCR performed similarly general touchscreen training LDR training. However, late testing, reached first more quickly had accurate vs. specifically when was challenging (lit squares close together "small separation"). Also, achieved reversals mice. Supporting specific influence behavior, did not differ total distance traveled time spent closed arms EPM. inducible LEC-DG activity, neurogenesis increased. These data indicate better This work advances fundamental translational neuroscience knowledge relevant two functions critical survival - suggests merits exploration as therapeutic target normalize dysfunctional output.

Language: Английский

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