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.

• Klíčová slova
• Alzheimer’s disease, TgF344-AD rats, place cell directionality, place field size, spatial memory,
• MeSH
• Alzheimerova nemoc * patofyziologie   MeSH
• amyloidový prekurzorový protein beta genetika   MeSH
• hipokampální oblast CA1 patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• modely nemocí na zvířatech * MeSH
• poruchy paměti etiologie   patofyziologie   MeSH
• potkani inbrední F344 MeSH
• potkani transgenní * MeSH
• prostorová paměť fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidový prekurzorový protein beta 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
• epizodická paměť * MeSH
• hipokampus MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• plži * MeSH
• podněty MeSH
• prostorová paměť MeSH
• rozpomínání MeSH
• savci MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Before the course of Alzheimer's disease fully manifests itself and largely impairs a patient's cognitive abilities, its progression has already lasted for a considerable time without being noticed. In this project, we mapped the development of spatial orientation impairment in an active place avoidance task-a highly sensitive test for mild hippocampal damage. We tested vision, anxiety and spatial orientation performance at four age levels of 4, 6, 9, and 12 months across male and female TgF-344 AD rats carrying human genes for presenilin-1 and amyloid precursor protein. We found a progressive deterioration of spatial navigation in transgenic animals, beginning already at the age of 4 months, that fully developed at 6 months of age across both male and female groups, compared to their age-matched controls. In addition, we described the gradual vision impairment that was accentuated in females at the age of 12 months. These results indicate a rather early onset of cognitive impairment in the TgF-344 AD Alzheimer's disease model, starting earlier than shown to date, and preceding the reported development of amyloid plaques.

• Klíčová slova
• Alzheimer’s disease, TgF-344 AD, navigation, spatial memory,
• Publikační typ
• časopisecké články MeSH