Impairment of visual cortical plasticity by amyloid-beta species

William, Christopher; Stern, Mark A.; Pei, Xuewei; Saqran, Lubna; Ramani, Margish; Frosch, Matthew P.; Hyman, Bradley T.

doi:10.1016/j.nbd.2021.105344

Cited by 9 publications

(11 citation statements)

References 50 publications

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“…Neuronal hyperactivity and is also observed in the visual cortex of AD patients [52,54,60,73]. Likewise, many mouse models of AD exhibit structural and functional deficits in the visual cortex [1,2,23,51,53,[74][75][76][77][78][79][80][81]. We recently found that visual cortex hyperactivity disrupts local functional connectivity and impairs visual recognition memory in a mouse model of amyloidosis [1].…”

Section: Introductionmentioning

confidence: 98%

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer’s disease

L’Esperance

McGhee

Davidson

et al. 2023

Preprint

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Hyperactivity is observed in early Alzheimers disease (AD) in multiple brain regions, including the visual cortex. We recently found that the postsynaptic structures favor visual cortex hyperactivity, which disrupts functional connectivity and leads to visual recognition memory deficits in a mouse AD model. It is unclear whether presynaptic structures also favor hyperactivity and whether hyperactivity depends on the target or source of presynaptic terminals. In addition, it is not well understood whether the functional connectivity of brain regions under nonpathological conditions predicts their hyperactivity in amyloid pathology. We used c-Fos immunolabeling under resting state conditions to map brain-wide neural activity and performed network analysis. We also quantified excitatory and inhibitory presynaptic terminals in hyperactive and non-hyperactive brain regions.We found that hyperactivity in the visual network originates in the cortex, and brain regions highly connected to the primary visual cortex in nonpathological conditions tend to be hyperactive in amyloid pathology. Immunolabeling presynaptic terminals from subcortical and cortical neurons show that the source rather than the target brain regions determine the vulnerability of synapses. Furthermore, we observed a reduction in presynaptic structures selectively in the hyperactive region, indicating presynaptic changes are unfavorable to hyperactivity. Brain regions with higher functional connectivity under nonpathological conditions are vulnerable to hyperactivity in amyloid pathology. Furthermore, presynapse loss may serve as an adaptation to maintain neuronal activity homeostasis.

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Section: Introductionmentioning

confidence: 98%

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer’s disease

L’Esperance

McGhee

Davidson

et al. 2023

Preprint

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show abstract

“… 35 Although the visual cortex does not display overt neurodegeneration early in AD, it is vulnerable to amyloid accumulation in patients and AD models. 36 - 40 …”

Section: Introductionmentioning

confidence: 99%

Excitation-inhibition imbalance disrupts visual familiarity in amyloid and non-pathology conditions

et al. 2023

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“…ocular dominance plasticity (ODP). ODP may be a more sensitive readout of abnormalities in circuit functions than or behavioral phenotypes [46][47][48]. We show that after monocular visual deprivation, 5XFAD mice lack ODP in VC during the normal critical period.…”

Section: Discussionmentioning

confidence: 76%

“…We cannot attribute these observed plasticity changes to APP or to intracellular Aβ production, which may be present at the age tested 48]. It has also been previously reported that mice that express mutant alleles of amyloid precursor protein (APPswe) and Pre-senilin1 (PS1dE9), and mice that only express APPswe alone or different species of Aβ (both Aβ40 and Aβ42) show disrupted ocular dominance plasticity in visual cortex [46,48], suggesting that mutant APP overexpression may impair plasticity through production of Aβ.…”

Section: Discussionmentioning

confidence: 90%

Early impairment of cortical circuit plasticity and connectivity in the 5XFAD Alzheimer’s disease mouse model

Chen

Wei

et al. 2022

Transl Psychiatry

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Genetic risk factors for neurodegenerative disorders, such as Alzheimer’s disease (AD), are expressed throughout the life span. How these risk factors affect early brain development and function remain largely unclear. Analysis of animal models with high constructive validity for AD, such as the 5xFAD mouse model, may provide insights on potential early neurodevelopmental effects that impinge on adult brain function and age-dependent degeneration. The 5XFAD mouse model over-expresses human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations. It is unclear how the expression of these mutant proteins affects early developing brain circuits. We found that the prefrontal cortex (PFC) layer 5 (L5) neurons in 5XFAD mice exhibit transgenic APP overloading at an early post-weaning age. Impaired synaptic plasticity (long-term potentiation, LTP) was seen at 6–8 weeks age in L5 PFC circuit, which was correlated with increased intracellular APP. APP overloading was also seen in L5 pyramidal neurons in the primary visual cortex (V1) during the critical period of plasticity (4–5 weeks age). Whole-cell patch clamp recording in V1 brain slices revealed reduced intrinsic excitability of L5 neurons in 5XFAD mice, along with decreased spontaneous miniature excitatory and inhibitory inputs. Functional circuit mapping using laser scanning photostimulation (LSPS) combined with glutamate uncaging uncovered reduced excitatory synaptic connectivity onto L5 neurons in V1, and a more pronounced reduction in inhibitory connectivity, indicative of altered excitation and inhibition during VC critical period. Lastly, in vivo single-unit recording in V1 confirmed that monocular visual deprivation-induced ocular dominance plasticity during critical period was impaired in 5XFAD mice. Our study reveals plasticity deficits across multiple cortical regions and indicates altered early cortical circuit developmental trajectory as a result of mutant APP/PS1 over-expression.

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Impairment of visual cortical plasticity by amyloid-beta species

Cited by 9 publications

References 50 publications

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer’s disease

Functional connectivity favors aberrant visual network c-Fos expression accompanied by cortical synapse loss in a mouse model of Alzheimer’s disease

Excitation-inhibition imbalance disrupts visual familiarity in amyloid and non-pathology conditions

Early impairment of cortical circuit plasticity and connectivity in the 5XFAD Alzheimer’s disease mouse model

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