Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy

Loreth, Desirée; Ozmen, Laurence; Revel, Florent G.; Knoflach, Frédéric; Wetzel, Philine; Frotscher, Michael; Metzger, Friedrich; Kretz, Oliver

doi:10.1016/j.nbd.2012.03.011

Cited by 49 publications

(56 citation statements)

References 91 publications

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“…Many physiological stimuli, such as exploration of novel environments, aging, or pathological conditions such as neurodegenerative diseases, affect the MS-DG GABAergic network. For instance, in a triple transgenic mouse model of Alzheimer’s disease (AD), selective loss of MS GABAergic (but not cholinergic) neurons and dentate interneurons (including PV neurons) were observed (Loreth et al, 2012). Furthermore, these mice displayed an aberrant initial increase in neurogenesis followed by a decrease of adult hippocampal neurogenesis at the later stage (Kuhn et al, 2007; Lazarov and Marr, 2010).…”

Section: Discussionmentioning

confidence: 99%

Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

et al. 2017

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Summary The quiescence of adult neural stem cells (NSCs) is regulated by local parvalbumin (PV) interneurons within the dentate gyrus (DG). Little is known about how local PV interneurons communicate with distal brain regions to regulate NSCs and hippocampal neurogenesis. Here we identify GABAergic projection neurons from the medial septum (MS) as the major afferents to dentate PV interneurons. Surprisingly, dentate PV interneurons are depolarized by GABA signaling, which is in sharp contrast to most mature neurons hyperpolarized by GABA. Functionally, these long-range GABAergic inputs are necessary and sufficient to maintain adult NSC quiescence, and ablating them leads to NSC activation and subsequent depletion of the NSC pool. Taken together, these findings delineate a GABAergic network involving long-range GABAergic projection neurons and local PV interneurons that couples dynamic brain activity to the neurogenic niche in controlling NSC quiescence and hippocampal neurogenesis.

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Section: Discussionmentioning

confidence: 99%

Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

et al. 2017

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“…Simon et al found signs of neurodegeneration in the CA1 and entorhinal cortex in amyloid precursor protein transgenic mice, while Beauquis et al discovered that these mice had reduced hippocampal volume with fewer pyramidal and granular neurons at 5 months of age [40,41]. Studies have also found degeneration of specific types of neurons in transgenic mice, including GABAergic septo-hippocampal neurons and calretinin interneurons [42,43]. …”

Section: Discussionmentioning

confidence: 99%

Amyloid Burden in Cognitively Normal Elderly is Associated with Preferential Hippocampal Subfield Volume Loss

Hsu

Shou

Benzinger

et al. 2015

JAD

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The earliest sites of brain atrophy in Alzheimer’s disease are in the medial temporal lobe, following widespread cerebral cortical amyloid deposition. We assessed 74 cognitively normal participants with clinical measurements, Aβ-PET imaging, MRI, and a newly developed technique for MRI-based hippocampal subfield segmentation to determine the differential association of amyloid deposition and hippocampal subfield volume. Compared to amyloid-negative participants, amyloid-positive participants had significantly smaller hippocampal tail, presubiculum, subiculum, and total hippocampal gray matter volumes. We conclude that, prior to the development of cognitive impairment, atrophy in particular hippocampal subfields (HS) occurs preferentially with Aβ accumulation.

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“…Specifically, those expressing calcium binding proteins parvalbumin, calbindin and calretinin, resulting in alterations in GABAergic interneuron populations and paralleling interneuron loss in human AD patients [47]–[49]. Recently, degeneration of GABAergic interneurons in DG expressing Neuropeptide Y was seen in a novel triple-transgenic AD model (TauPS2APP mouse; [50]). Interestingly, enhanced LTP to PP stimulation was seen in this triple mutation mouse in DG ( in vitro ), therefore, it is possible that loss of GABAergic tone in this and other models could contribute to hyper-excitability originating in DG [33]–[35], [50].…”

Section: Discussionmentioning

confidence: 99%

Increased Hippocampal Excitability in the 3xTgAD Mouse Model for Alzheimer's Disease In Vivo

2014

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Mouse Alzheimer's disease (AD) models develop age- and region-specific pathology throughout the hippocampal formation. One recently established pathological correlate is an increase in hippocampal excitability in vivo. Hippocampal pathology also produces episodic memory decline in human AD and we have shown a similar episodic deficit in 3xTg AD model mice aged 3–6 months. Here, we tested whether hippocampal synaptic dysfunction accompanies this cognitive deficit by probing dorsal CA1 and DG synaptic responses in anaesthetized, 4–6 month-old 3xTgAD mice. As our previous reports highlighted a decline in episodic performance in aged control mice, we included aged cohorts for comparison. CA1 and DG responses to low-frequency perforant path stimulation were comparable between 3xTgAD and controls at both age ranges. As expected, DG recordings in controls showed paired-pulse depression; however, paired-pulse facilitation was observed in DG and CA1 of young and old 3xTgAD mice. During stimulus trains both short-latency (presumably monosynaptic: ‘direct’) and long-latency (presumably polysynaptic: ‘re-entrant’) responses were observed. Facilitation of direct responses was modest in 3xTgAD animals. However, re-entrant responses in DG and CA1 of young 3xTgAD mice developed earlier in the stimulus train and with larger amplitude when compared to controls. Old mice showed less DG paired-pulse depression and no evidence for re-entrance. In summary, DG and CA1 responses to low-frequency stimulation in all groups were comparable, suggesting no loss of synaptic connectivity in 3xTgAD mice. However, higher-frequency activation revealed complex change in synaptic excitability in DG and CA1 of 3xTgAD mice. In particular, short-term plasticity in DG and CA1 was facilitated in 3xTgAD mice, most evidently in younger animals. In addition, re-entrance was facilitated in young 3xTgAD mice. Overall, these data suggest that the episodic-like memory deficit in 3xTgAD mice could be due to the development of an abnormal hyper-excitable state in the hippocampal formation.

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Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy

Cited by 49 publications

References 91 publications

Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

Long-Range GABAergic Inputs Regulate Neural Stem Cell Quiescence and Control Adult Hippocampal Neurogenesis

Amyloid Burden in Cognitively Normal Elderly is Associated with Preferential Hippocampal Subfield Volume Loss

Increased Hippocampal Excitability in the 3xTgAD Mouse Model for Alzheimer's Disease In Vivo

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