BACKGROUND: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. OBJECTIVE: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. METHODS: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. RESULTS: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. CONCLUSIONS: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.
- MeSH
- Alzheimer Disease * physiopathology MeSH
- Amyloid beta-Protein Precursor genetics MeSH
- CA1 Region, Hippocampal physiopathology MeSH
- Hippocampus physiopathology MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal * MeSH
- Memory Disorders etiology physiopathology MeSH
- Rats, Inbred F344 MeSH
- Rats, Transgenic * MeSH
- Spatial Memory physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The dissociation between egocentric and allocentric reference frames is well established. Spatial coding relative to oneself has been associated with a brain network distinct from spatial coding using a cognitive map independently of the actual position. These differences were, however, revealed by a variety of tasks from both static conditions, using a series of images, and dynamic conditions, using movements through space. We aimed to clarify how these paradigms correspond to each other concerning the neural correlates of the use of egocentric and allocentric reference frames. We review here studies of allocentric and egocentric judgments used in static two- and three-dimensional tasks and compare their results with the findings from spatial navigation studies. We argue that neural correlates of allocentric coding in static conditions but using complex three-dimensional scenes and involving spatial memory of participants resemble those in spatial navigation studies, while allocentric representations in two-dimensional tasks are connected with other perceptual and attentional processes. In contrast, the brain networks associated with the egocentric reference frame in static two-dimensional and three-dimensional tasks and spatial navigation tasks are, with some limitations, more similar. Our review demonstrates the heterogeneity of experimental designs focused on spatial reference frames. At the same time, it indicates similarities in brain activation during reference frame use despite this heterogeneity.
- MeSH
- Humans MeSH
- Brain Mapping methods MeSH
- Judgment physiology MeSH
- Neuropsychological Tests MeSH
- Attention physiology MeSH
- Spatial Memory physiology MeSH
- Photic Stimulation methods MeSH
- Space Perception physiology MeSH
- Visual Perception physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Obesity and type 2 diabetes mellitus (T2DM) were characterized as risk factors for Alzheimer's disease (AD) development. Subsequently, T2DM drugs, such as liraglutide, were proven to be neuroprotective compounds attenuating levels of amyloid deposits, and tau hyperphosphorylation, both hallmarks of AD. The central anorexigenic effects of liraglutide inspired us to examine the potential neuroprotective effects of palm11-PrRP31, a strong anorexigenic analog with glucose-lowering properties, in THY-Tau22 mice overexpressing mutated human tau, a model of AD-like tau pathology. Seven-month-old THY-Tau22 mice were subcutaneously infused with palm11-PrRP31 for 2 months. Spatial memory was tested before and after the treatment, using a Y-maze. At the end of the treatment, mice were sacrificed by decapitation and hippocampi were dissected and analyzed by immunoblotting with specific antibodies. Treatment with palm11-PrRP31 resulted in significantly improved spatial memory. In the hippocampi of palm11-PrRP31-treated THY-Tau22 mice, tau protein phosphorylation was attenuated at Thr231, Ser396, and Ser404, the epitopes linked to AD progression. The mechanism of this attenuation remains unclear, since the activation of those kinases most implicated in tau hyperphosphorylation, such as GSK-3β, JNK, or MAPK/ERK1/2, remained unchanged by palm11-PrRP31 treatment. Furthermore, we observed a significant increase in the amount of postsynaptic density protein PSD95, and a non-significant increase of synaptophysin, both markers of increased synaptic plasticity, which could also result in improved spatial memory of THY-Tau22 mice treated with palm11-PrRP31. Palm11-PrRP31 seems to be a potential tool for the attenuation of neurodegenerative disorders in the brain. However, the exact mechanism of its action must be elucidated.
- MeSH
- Maze Learning drug effects physiology MeSH
- Phosphorylation drug effects MeSH
- Hippocampus drug effects metabolism pathology MeSH
- Prolactin-Releasing Hormone analogs & derivatives pharmacology therapeutic use MeSH
- Memory, Short-Term drug effects physiology MeSH
- Disease Models, Animal MeSH
- Mice, Transgenic MeSH
- Neuroprotective Agents pharmacology MeSH
- Memory Disorders drug therapy metabolism pathology MeSH
- Spatial Memory drug effects physiology MeSH
- tau Proteins metabolism MeSH
- Tauopathies drug therapy metabolism pathology psychology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Diagnostic Techniques, Neurological MeSH
- Executive Function physiology MeSH
- Cognition MeSH
- Cognitive Remediation methods MeSH
- Humans MeSH
- Neuropsychological Tests * MeSH
- Perception MeSH
- Spatial Navigation physiology MeSH
- Spatial Memory physiology MeSH
- Virtual Reality * MeSH
- Check Tag
- Humans MeSH
Hippocampal place cells represent different environments with distinct neural activity patterns. Following an abrupt switch between two familiar configurations of visual cues defining two environments, the hippocampal neural activity pattern switches almost immediately to the corresponding representation. Surprisingly, during a transient period following the switch to the new environment, occasional fast transitions between the two activity patterns (flickering) were observed (Jezek, Henriksen, Treves, Moser, & Moser, ). Here we show that an attractor neural network model of place cells with connections endowed with short-term synaptic plasticity can account for this phenomenon. A memory trace of the recent history of network activity is maintained in the state of the synapses, allowing the network to temporarily reactivate the representation of the previous environment in the absence of the corresponding sensory cues. The model predicts that the number of flickering events depends on the amplitude of the ongoing theta rhythm and the distance between the current position of the animal and its position at the time of cue switching. We test these predictions with new analysis of experimental data. These results suggest a potential role of short-term synaptic plasticity in recruiting the activity of different cell assemblies and in shaping hippocampal activity of behaving animals.
- MeSH
- Action Potentials physiology MeSH
- Time Factors MeSH
- Electroencephalography MeSH
- Hippocampus cytology MeSH
- Rats MeSH
- Brain Mapping MeSH
- Models, Neurological * MeSH
- Nerve Net physiology MeSH
- Neurons physiology MeSH
- Neuronal Plasticity physiology MeSH
- Cues MeSH
- Spatial Memory physiology MeSH
- Photic Stimulation MeSH
- Theta Rhythm physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Hippocampus MeSH
- Humans MeSH
- Grid Cells MeSH
- Spatial Memory * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
The processes that organize different thoughts and memories, allowing the separation of currently relevant and irrelevant information, are collectively known as cognitive control. The neuronal mechanisms of these processes can be investigated by place cell ensemble recordings during behaviors and environmental manipulations that present cognitive control challenges to selectively represent one of multiple possible alternative estimates of location. We review place cell studies that investigate responses to manipulations that dissociate the environment into two or more spatial frames of locations, often times to test notions of pattern separation. Manipulations, such as continuously rotating the recording chamber reveal that the ensemble discharge in hippocampus self-organizes into multiple, transiently-organized representations of space, each defined by the subset of coactive cells. Ensemble discharge in the hippocampus alternates between separate representations of frame-specific positions on timescales from 25 ms to several seconds. The dynamic, functional grouping of discharge into transiently co-active subsets of cells is predicted by the animal's changing behavioral needs. In addition to identifying neural correlates of cognitive control in hippocampus, these observations demonstrate that the separation of neuronal activity into distinctive representations depends on ongoing cognitive demands and that what can appear as noise, deviations from receptive field tuning, can substantially be the result of these internal knowledge-guided fluctuations. These findings inspire a new perspective that should be taken into account when investigating pattern separation--a perspective that emphasizes changes in hippocampal neural discharge that are happening on a short timescale and does not assume that patterns of neural discharge are steady and stationary across the several minutes of the recordings.
- MeSH
- Place Cells physiology MeSH
- Hippocampus physiology MeSH
- Rats MeSH
- Humans MeSH
- Models, Neurological * MeSH
- Spatial Memory physiology MeSH
- Spatial Learning physiology MeSH
- Space Perception physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- MeSH
- Hippocampus MeSH
- Humans MeSH
- Spatial Navigation * physiology MeSH
- Spatial Memory physiology MeSH
- Spatial Behavior physiology MeSH
- Spatial Learning * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Review MeSH
- Keywords
- Laboratoř neurofyziologie paměti,
- MeSH
- Academies and Institutes MeSH
- Humans MeSH
- Neurophysiology MeSH
- Neuropsychiatry MeSH
- Spatial Memory * physiology MeSH
- Research * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Introductory Journal Article MeSH
