Differential disruptions in population coding along the dorsal-ventral axis of CA1 in the APP/PS1 mouse model of Aß pathology.
PLoS Comput Biol
; 20(5): e1012085, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38709845
ABSTRACT
Alzheimer's Disease (AD) is characterized by a range of behavioral alterations, including memory loss and psychiatric symptoms. While there is evidence that molecular pathologies, such as amyloid beta (Aß), contribute to AD, it remains unclear how this histopathology gives rise to such disparate behavioral deficits. One hypothesis is that Aß exerts differential effects on neuronal circuits across brain regions, depending on the neurophysiology and connectivity of different areas. To test this, we recorded from large neuronal populations in dorsal CA1 (dCA1) and ventral CA1 (vCA1), two hippocampal areas known to be structurally and functionally diverse, in the APP/PS1 mouse model of amyloidosis. Despite similar levels of Aß pathology, dCA1 and vCA1 showed distinct disruptions in neuronal population activity as animals navigated a virtual reality environment. In dCA1, pairwise correlations and entropy, a measure of the diversity of activity patterns, were decreased in APP/PS1 mice relative to age-matched C57BL/6 controls. However, in vCA1, APP/PS1 mice had increased pair-wise correlations and entropy as compared to age matched controls. Finally, using maximum entropy models, we connected the microscopic features of population activity (correlations) to the macroscopic features of the population code (entropy). We found that the models' performance increased in predicting dCA1 activity, but decreased in predicting vCA1 activity, in APP/PS1 mice relative to the controls. Taken together, we found that Aß exerts distinct effects across different hippocampal regions, suggesting that the various behavioral deficits of AD may reflect underlying heterogeneities in neuronal circuits and the different disruptions that Aß pathology causes in those circuits.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Precursor de Proteína beta-Amiloide
/
Región CA1 Hipocampal
/
Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Año:
2024
Tipo del documento:
Article