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Eric R Kandel - One of the best experts on this subject based on the ideXlab platform.
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dopamine release from the locus coeruleus to the dorsal Hippocampus promotes spatial learning and memory
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Kimberly A Kempadoo, Eric R Kandel, Eugene V Mosharov, Se Joon Choi, David SulzerAbstract:Dopamine neurotransmission in the dorsal Hippocampus is critical for a range of functions from spatial learning and synaptic plasticity to the deficits underlying psychiatric disorders such as attention-deficit hyperactivity disorder. The ventral tegmental area (VTA) is the presumed source of dopamine in the dorsal Hippocampus. However, there is a surprising scarcity of VTA dopamine axons in the dorsal Hippocampus despite the dense network of dopamine receptors. We have explored this apparent paradox using optogenetic, biochemical, and behavioral approaches and found that dopaminergic axons and subsequent dopamine release in the dorsal Hippocampus originate from neurons of the locus coeruleus (LC). Photostimulation of LC axons produced an increase in dopamine release in the dorsal Hippocampus as revealed by high-performance liquid chromatography. Furthermore, optogenetically induced release of dopamine from the LC into the dorsal Hippocampus enhanced selective attention and spatial object recognition via the dopamine D1/D5 receptor. These results suggest that spatial learning and memory are energized by the release of dopamine in the dorsal Hippocampus from noradrenergic neurons of the LC. The present findings are critical for identifying the neural circuits that enable proper attention selection and successful learning and memory.
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reversible inhibition of creb atf transcription factors in region ca1 of the dorsal Hippocampus disrupts Hippocampus dependent spatial memory
Neuron, 2002Co-Authors: Christopher Pittenger, Eric R Kandel, Yan You Huang, Ronald F Paletzki, Roussoudan Bourtchouladze, Heather Scanlin, Svetlana VronskayaAbstract:CREB is critical for long-lasting synaptic and behavioral plasticity in invertebrates. Its role in the mammalian Hippocampus is less clear. We have interfered with CREB family transcription factors in region CA1 of the dorsal Hippocampus. This impairs learning in the Morris water maze, which specifically requires the dorsal Hippocampus, but not context conditioning, which does not. The deficit is specific to long-term memory, as shown in an object recognition task. Several forms of late-phase LTP are normal, but forskolin-induced and dopamine-regulated potentiation are disrupted. These experiments represent the first targeting of the dorsal Hippocampus in genetically modified mice and confirm a role for CREB in Hippocampus-dependent learning. Nevertheless, they suggest that some experimental forms of plasticity bypass the requirement for CREB.
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long term potentiation in the Hippocampus is blocked by tyrosine kinase inhibitors
Nature, 1991Co-Authors: Thomas J Odell, Eric R Kandel, Seth G N GrantAbstract:LONG-TERM potentiation (LTP) in the Hippocampus is thought to contribute to memory formation. In the Ca1 region, LTP requires the NMDA (N-methyl-D-aspartate) receptor-dependent influx of Ca2+ and activation of serine and threonine protein kinases. Because of the high amount of protein tyrosine kinases in Hippocampus and cerebellum1,2, two regions implicated in learning and memory, we examined the possible additional requirement of tyrosine kinase activity in LTP. We first examined the specificity in brain of five inhibitors of tyrosine kinase3–5 (Table 1) and found that two of them, lavendustin A and genistein, showed substantially greater specificity for tyrosine kinase from Hippocampus6 than for three serine–threonine kinases: protein kinase A, protein kinase C, and Ca2+/calmodulin kinase II. Lavendustin A and genistein selectively blocked the induction of LTP when applied in the bath or injected into the postsynaptic cell. By contrast, the inhibitors had no effect on the established LTP, on normal synaptic transmission, or on the neurotransmitter actions attributable to the actions of protein kinase A or protein kinase C. These data suggest that tyrosine kinase activity could be required postsynaptically for long-term synaptic plasticity in the Hippocampus. As Ca2+ cal-modulin kinase II or protein kinase C seem also to be required7, 8, the tyrosine kinases could participate postsynaptically in a kinase network together with serine and threonine kinases.
Veronique D Bohbot - One of the best experts on this subject based on the ideXlab platform.
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Impact of video games on plasticity of the Hippocampus
Molecular Psychiatry, 2018Co-Authors: G L West, K Konishi, M Diarra, J Benady-chorney, B L Drisdelle, L Dahmani, D J Sodums, F Lepore, P Jolicoeur, Veronique D BohbotAbstract:The Hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the Hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the Hippocampus in participants using non-spatial memory strategies. Conversely, participants who use Hippocampus-dependent spatial strategies showed increased grey matter in the Hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the Hippocampus or the functionally connected entorhinal cortex. A third study replicated the effect of action video game training on grey matter in the Hippocampus. These results show that video games can be beneficial or detrimental to the hippocampal system depending on the navigation strategy that a person employs and the genre of the game.
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decreased functional magnetic resonance imaging activity in the Hippocampus in favor of the caudate nucleus in older adults tested in a virtual navigation task
Hippocampus, 2013Co-Authors: Kyoko Konishi, Nicole Etchamendy, Aline Marighetto, Natasha Rajah, Veronique D BohbotAbstract:The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the Hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the Hippocampus and caudate nucleus, respectively. Therefore, since the proportion of people using spatial strategies decreases with normal aging, we hypothesized that it was responsible for the observed decreases in fMRI activity in the Hippocampus reported in the literature. The aim of this study was to examine the effects of aging on the Hippocampus and caudate nucleus during navigation while taking into account individual navigational strategies. Young (N = 23) and older adults (N = 29) were tested using fMRI on the Concurrent Spatial Discrimination Learning Task, a radial task that dissociates between spatial and response strategies (in Stage 2) after participants reached criteria (in Stage 1). Success on Stage 2 requires that participants have encoded the spatial relationship between the target object and environmental landmarks, that is, the spatial strategy. While older adults required more trials, all participants reached criterion. fMRI results showed that, as a group, young adults had significant activity in the Hippocampus as opposed to older adults who instead had significant activity in the caudate nucleus. Importantly, individual differences showed that the older participants who used a spatial strategy to solve the task had significant activity in the Hippocampus. These findings suggest that the aging process involves a shift from using the Hippocampus toward the caudate nucleus during navigation but that activity in the Hippocampus is sustained in a subset of healthy older adults engaged in spatial strategies. © 2013 Wiley Periodicals, Inc.
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Decreased functional magnetic resonance imaging activity in the Hippocampus in favor of the caudate nucleus in older adults tested in a virtual navigation task
Hippocampus, 2013Co-Authors: Kyoko Konishi, Nicole Etchamendy, Aline Marighetto, Natasha Rajah, Shumita Roy, Veronique D BohbotAbstract:The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the Hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the Hippocampus and caudate nucleus, respectively. Therefore, since the proportion of people using spatial strategies decreases with normal aging, we hypothesized that it was responsible for the observed decreases in fMRI activity in the Hippocampus reported in the literature. The aim of this study was to examine the effects of aging on the Hippocampus and caudate nucleus during navigation while taking into account individual navigational strategies. Young (N = 23) and older adults (N = 29) were tested using fMRI on the Concurrent Spatial Discrimination Learning Task, a radial task that dissociates between spatial and response strategies (in Stage 2) after participants reached criteria (in Stage 1). Success on Stage 2 requires that participants have encoded the spatial relationship between the target object and environmental landmarks, that is, the spatial strategy. While older adults required more trials, all participants reached criterion. fMRI results showed that, as a group, young adults had significant activity in the Hippocampus as opposed to older adults who instead had significant activity in the caudate nucleus. Importantly, individual differences showed that the older participants who used a spatial strategy to solve the task had significant activity in the Hippocampus. These findings suggest that the aging process involves a shift from using the Hippocampus toward the caudate nucleus during navigation but that activity in the Hippocampus is sustained in a subset of healthy older adults engaged in spatial strategies.
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Gray Matter Differences Correlate with Spontaneous Strategies in a Human Virtual Navigation Task
The Journal of Neuroscience, 2007Co-Authors: Veronique D Bohbot, Brook Thorndycraft, Giuseppe Iaria, Jason P. Lerch, Alex P. ZijdenbosAbstract:Young healthy participants spontaneously use different strategies in a virtual radial maze, an adaptation of a task typically used with rodents. Functional magnetic resonance imaging confirmed previously that people who used spatial memory strategies showed increased activity in the Hippocampus, whereas response strategies were associated with activity in the caudate nucleus. Here, voxel based morphometry was used to identify brain regions covarying with the navigational strategies used by individuals. Results showed that spatial learners had significantly more gray matter in the Hippocampus and less gray matter in the caudate nucleus compared with response learners. Furthermore, the gray matter in the Hippocampus was negatively correlated to the gray matter in the caudate nucleus, suggesting a competitive interaction between these two brain areas. In a second analysis, the gray matter of regions known to be anatomically connected to the Hippocampus, such as the amygdala, parahippocampal, perirhinal, entorhinal and orbitofrontal cortices were shown to covary with gray matter in the Hippocampus. Because low gray matter in the Hippocampus is a risk factor for Alzheimer's disease, these results have important implications for intervention programs that aim at functional recovery in these brain areas. In addition, these data suggest that spatial strategies may provide protective effects against degeneration of the Hippocampus that occurs with normal aging.
Richardson N Leao - One of the best experts on this subject based on the ideXlab platform.
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salicylate induces anxiety like behavior and slow theta oscillation and abolishes the relationship between running speed and fast theta oscillation frequency
Hippocampus, 2019Co-Authors: Jessica Winne, Rafael Franzon, Aron De Miranda, Thawann Malfatti, Joao Patriota, Sanja Mikulovic, Katarina E Leao, Richardson N LeaoAbstract:: Salicylate intoxication is a cause of tinnitus in humans and it is often used to produce tinnitus-like perception in animal models. Here, we assess whether salicylate induces anxiety-like electrophysiological and behavioral signs. Using microwire electrode arrays, we recorded local field potential in the ventral and, in some experiments dorsal Hippocampus, in an open field arena 1 hr after salicylate (300 mg/kg) injection. We found that animals treated with salicylate moved dramatically less than saline treated animals. Salicylate-treated animals showed a strong 4-6 Hz (type 2) oscillation in the ventral Hippocampus (with smaller peaks in dorsal Hippocampus electrodes). Coherence in the 4-6 Hz-theta band was low in the ventral and dorsal Hippocampus when compared to movement-related theta coherence (7-10 Hz). Moreover, movement related theta oscillation frequency decreased and its dependency on running speed was abolished. Our results suggest that salicylate-induced theta is mostly restricted to the ventral Hippocampus. Slow theta has been classically associated to anxiety-like behaviors. Here, we show that salicylate application can consistently generate low frequency theta in the ventral Hippocampus. Tinnitus and anxiety show strong comorbidity and the increase in ventral Hippocampus low frequency theta could be part of this association.
Matthew A Wilson - One of the best experts on this subject based on the ideXlab platform.
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anatomical substrates for direct interactions between Hippocampus medial prefrontal cortex and the thalamic nucleus reuniens
Brain Structure & Function, 2014Co-Authors: Carmen Varela, S Kumar, Jian Yang, Matthew A WilsonAbstract:The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the Hippocampus, and has been suggested to modulate interactions between these regions, such as spindle–ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the Hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral Hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the Hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and Hippocampus by looking for double-labeled cells in reuniens and Hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal Hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral Hippocampus. Feedback from Hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and Hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and Hippocampus. Cells with collaterals in the Hippocampus–reuniens–mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior.
Raymond P. Kesner - One of the best experts on this subject based on the ideXlab platform.
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time dependent relationship between the dorsal Hippocampus and the prefrontal cortex in spatial memory
The Journal of Neuroscience, 2003Co-Authors: Raymond P. KesnerAbstract:The prefrontal cortex and the dorsal Hippocampus have been studied extensively for their significant roles in spatial working memory. A possible time-dependent functional relationship between the prefrontal cortex and the dorsal Hippocampus in spatial working memory was tested. A combined lesion and pharmacological inactivation technique targeting both the dorsal Hippocampus and the medial prefrontal cortex was used (i.e., axon-sparing lesions of the dorsal Hippocampus combined with reversible inactivation of the medial prefrontal cortex, or vice versa, within a subject). A delayed nonmatching-to-place task on a radial eight-arm maze with short-term (i.e., 10 sec) versus intermediate-term (i.e., 5 min) delays was used as a behavioral paradigm. Here we report that the dorsal Hippocampus and the medial prefrontal cortex process short-term spatial memory in parallel, serving as a compensatory mechanism for each other. The role of the dorsal Hippocampus, however, becomes highlighted as the time-window for memory (i.e., delay) shifts from short-term to a delay period (i.e., intermediate-term) exceeding the short-term range. The results indicate that the time window of memory is a key factor in dissociating multiple memory systems.
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Memory for spatial location: Functional dissociation of entorhinal cortex and Hippocampus
Psychobiology, 1994Co-Authors: Mary E. Hunt, Raymond P. Kesner, Roger B. EvansAbstract:To test whether there is a functional dissociation between the Hippocampus and entorhinal cortex, rats were trained on a variable spatial-location matching-to-sample (working memory) task with various delays. After training, rats with entorhinal cortex, entorhinal-cortex-plus-Hippocampus/subiculum, Hippocampus, control, or cortical control lesions were tested for performance within the task. Results indicated that in the variable spatial-location condition relative to the control and cortical controls, all lesioned groups showed a profound impairment in performance of the task across all delays. They were subsequently tested for acquisition of a constant spatial location task. In the constant spatial-location condition, the entorhinal cortex and entorhinal-cortex-plus-Hippocampus/subiculum lesioned groups did not learn the task, whereas the hippocampal lesioned group did. It is suggested that there is a functional dissociation between the Hippocampus and the entorhinal cortex. It is proposed that the Hippocampus encodes new spatial information within a working-memory system, whereas the entorhinal cortex represents spatial information within a reference-memory system as part of a spatial cognitive map.
