Alzheimer's disease (AD), a leading cause of dementia worldwide, is a multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused by various genetic and environmental factors. Numerous transgenic rodent models have been developed to understand AD pathology development and progression. The TgF344-AD rat model is a double transgenic model that carries two human gene mutations: APP with the Swedish mutation and PSEN-1 with delta exon 9 mutations. This model exhibits a complete repertoire of AD pathology in an age-dependent manner. This review summarizes multidisciplinary research insights gained from studying TgF344-AD rats in the context of AD pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, and altered sleep architecture; behavioral studies highlighting impaired spatial memory; alterations in excitatory-inhibitory systems; and molecular and physiological changes in TgF344-AD rats emphasizing their age-related effects. Additionally, the impact of various interventions studied in the model is compiled, underscoring their role in bridging gaps in understanding AD pathogenesis. The TgF344-AD rat model offers significant potential in identifying biomarkers for early detection and therapeutic interventions, providing a robust platform for advancing translational AD research. Key words Alzheimer's disease, Transgenic AD models, TgF344-AD rats, Spatial coding.

• MeSH
• Alzheimer Disease * genetics   pathology   metabolism   physiopathology   MeSH
• Amyloid beta-Protein Precursor genetics   MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal * MeSH
• Brain * pathology   metabolism   physiopathology   MeSH
• Mutation MeSH
• Rats, Inbred F344 MeSH
• Rats, Transgenic MeSH
• Presenilin-1 genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Amyloid beta-Protein Precursor MeSH
• Presenilin-1 MeSH

The hippocampus plays a crucial role in the formation and retrieval of spatial memory across mammals and episodic memory in humans. Episodic and spatial memories can be retrieved irrespective of the subject's awake behavioral state and independently of its actual spatial context. However, the nature of hippocampal network activity during such out-context retrieval has not been described so far. Theoretically, context-independent spatial memory retrieval suggests a shift of the hippocampal spatial representations from coding the current spatial context to coding the remembered environment. In this study we show in rats that the CA3 neuronal population can switch spontaneously across representations and transiently activate another stored familiar spatial pattern without direct external sensory cuing. This phenomenon qualitatively differs from the well-described sharp wave-related pattern reactivations during immobility. Here, it occurs under the theta oscillatory state during active exploration and reflects the preceding experience of sudden environmental change. The respective out-context coding spikes appeared later in the theta cycle than the in-context ones. Finally, the experience also induced the emergence of population vectors with a co-expression of both codes segregated into different phases of the theta cycle.

• MeSH
• Memory, Episodic * MeSH
• Hippocampus MeSH
• Rats MeSH
• Humans MeSH
• Gastropoda * MeSH
• Cues MeSH
• Spatial Memory MeSH
• Mental Recall MeSH
• Mammals MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Animals can organize their behavior with respect to other moving animals or objects; when hunting or escaping a predator, when migrating in groups or during various social interactions. In rats, we aimed to characterize spatial behaviors relative to moving objects and to explore the cognitive mechanisms controlling these behaviors. Three groups of animals were trained to avoid a mild foot-shock delivered in one of three positions: either in front, on the left side, or on the right side of a moving robot. We showed the rats can recognize and avoid these specific areas. The avoidance behavior specific for the left or right side of the robot demonstrated animals not only react to "simple" stimuli such as increasing noise level or growing retinal image of an approaching object, but they process their spatial position relative to the object. Using an all-white robot without prominent visual patterns that would distinguish its different sides, we showed that the behavior does not depend on responses to prominent visual patterns, but that the rats can guide their navigation according to geometrical spatial relationship relative to the moving object. Rats' competence for navigation in space defined by a moving object resembles navigation abilities in stationary space. Recording of hippocampal single unit activity during rat's interaction with the robot proved feasibility of the task to uncover neuronal mechanism of this type of navigation.

• Keywords
• dynamic environment, hippocampus, moving object, navigation, place cells, robot,
• Publication type
• Journal Article MeSH

The hippocampus is well known for its critical involvement in spatial memory and information processing. In this study, we examined the effect of bilateral hippocampal inactivation with tetrodotoxin (TTX) in an "enemy avoidance" task. In this paradigm, a rat foraging on a circular platform (82 cm diameter) is trained to avoid a moving robot in 20-min sessions. Whenever the rat is located within 25 cm of the robot's center, it receives a mild electrical foot shock, which may be repeated until the subject makes an escape response to a safe distance. Seventeen young male Long-Evans rats were implanted with cannulae aimed at the dorsal hippocampus 14 d before the start of the training. After 6 d of training, each rat received a bilateral intrahippocampal infusion of TTX (5 ng in 1 μL) 40 min before the training session on day 7. The inactivation severely impaired avoidance of a moving robot (n = 8). No deficit was observed in a different group of rats (n = 9) that avoided a stable robot that was only displaced once in the middle of the session, showing that the impairment was not due to a deficit in distance estimation, object-reinforcement association, or shock sensitivity. This finding suggests a specific role of the hippocampus in dynamic cognitive processes required for flexible navigation strategies such as continuous updating of information about the position of a moving stimulus.

• MeSH
• Behavior, Animal physiology   MeSH
• Hippocampus anatomy & histology   drug effects   physiology   MeSH
• Rats MeSH
• Locomotion physiology   MeSH
• Rats, Long-Evans MeSH
• Tetrodotoxin pharmacology   MeSH
• Avoidance Learning physiology   MeSH
• Motion Perception physiology   MeSH
• Space Perception physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Tetrodotoxin MeSH