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Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.

ABSTRACT: The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-? (A?) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC abnormalities occur in 2- to 4-month-old Tg2576 mice, an age before A? deposition and where previous studies suggest that there are few behavioral impairments. First we show, using a sandwich enzyme-linked immunosorbent assay, that soluble human A?40 and A?42 are detectable in the EC of 2-month-old Tg2576 mice before A? deposition. We then demonstrate that 2- to 4-month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next, we show that defects in neuronal nuclear antigen expression and myelin uptake occur in the superficial layers of the EC in 2- to 4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg(2+)]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages and suggest that altered excitability occurs before extensive plaque pathology.

SUBMITTER: Duffy AM

PROVIDER: S-EPMC4268389 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.

Duffy Aine M AM Morales-Corraliza Jose J Bermudez-Hernandez Keria M KM Schaner Michael J MJ Magagna-Poveda Alejandra A Mathews Paul M PM Scharfman Helen E HE

Neurobiology of aging 20140711 1

The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC abnormalities occur in 2- to 4-month-old Tg2576 mice, an age before Aβ deposition and where previous studies suggest that there are few behavioral impairments. First we show, using a sandwich enzyme-linked immunosorbent assay, that soluble human Aβ40 and ...[more]

PMID: 25109765

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Project description:The claustrum, a subcortical structure situated between the insular cortex and striatum, is reciprocally connected with almost all neocortical regions. Based on this connectivity, the claustrum has been postulated to integrate multisensory information and, in turn, coordinate widespread cortical activity. Although studies have identified how sensory information is mapped onto the claustrum, the function of individual topographically arranged claustro-cortical pathways has been little explored. Here, we investigated the organization and function of identified claustro-cortical pathways in mice using multiple anatomical and optogenetic techniques. Retrograde and anterograde tracing demonstrated that the density of anterior claustrum-to-cortical projection differs substantially depending on the target cortical areas. One of the major targets was the medial entorhinal cortex (MEC) and the MEC-projecting claustral neurons were largely segregated from the neurons projecting to primary cortices M1, S1, or V1. Exposure to a novel environment induced c-Fos expression in a substantial number of MEC-projecting claustral neurons and some M1/S1/V1-projecting claustral neurons. Optogenetic silencing of the MEC-projecting claustral neurons during contextual fear conditioning impaired later memory retrieval without affecting basal locomotor activity or anxiety-related behavior. These results suggest that the dense, anterior claustro-MEC pathway that is largely separated from other claustro-cortical pathways is activated by novel context and modulates the MEC function in contextual memory.Significance statementThe claustrum is a poorly understood subcortical structure reciprocally connected with widespread neocortical regions. We investigated the organization and function of identified claustro-cortical projections in mice using pathway-specific approaches. Anatomical tracing showed that the density of anterior claustrum-to-cortical projection is dependent on the target cortical areas and that the medial entorhinal cortex (MEC) is one of the major projection targets. Novel context exposure activated multiple claustro-cortical pathways and a large fraction of the activated neurons projected to the MEC. Optogenetic silencing of the claustro-MEC pathway during contextual fear learning suppressed subsequent memory retrieval. These results suggest that the dense claustro-MEC pathway is activated by novel context and modulates MEC function in contextual memory.

Dataset Information

Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.

Publications

Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.

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