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• W4386245024 endingPage "6949" @default.
• W4386245024 startingPage "6930" @default.
• W4386245024 abstract "A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and CA2 pyramidal neurons (PNs). A role for CA2 in seizure generation was suggested based on findings of a reduction in CA2 synaptic inhibition (Williamson and Spencer, 1994) and the presence of interictal-like spike activity in CA2 in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-induced status epilepticus (PILO-SE) mouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study, we explored the cellular basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches in PILO-SE male and female mice. We report a widespread decrease in the density of pro-cholecystokinin-immunopositive (CCK+) interneurons and a functional impairment of CCK+ interneuron-mediated inhibition of CA2 PNs. We also found a disruption in the perisomatic perineuronal net in the CA2 stratum pyramidale. Such pathologic alterations may contribute to an enhanced excitation of CA2 PNs and CA2-dependent seizure activity in the PILO-SE mouse model.SIGNIFICANCE STATEMENT Impaired synaptic inhibition in hippocampal circuits has been identified as a key feature that contributes to the emergence and propagation of seizure activity in human patients and animal models of temporal lobe epilepsy (TLE). Among the hippocampal subfields, the CA2 region is particularly resilient to seizure-associated neurodegeneration and has been suggested to play a key role in seizure activity in TLE. Here we report that perisomatic inhibition of CA2 pyramidal neurons mediated by cholecystokinin-expressing interneurons is selectively reduced in acute hippocampal slices from epileptic mice. Parvalbumin-expressing interneurons, in contrast, appear relatively conserved in epileptic mice. These findings advance our understanding of the cellular mechanisms underlying inhibitory disruption in hippocampal circuits in a mouse model of spontaneous recurring seizures." @default.
• W4386245024 created "2023-08-30" @default.
• W4386245024 creator A5013260521 @default.
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• W4386245024 creator A5084011091 @default.
• W4386245024 creator A5087367713 @default.
• W4386245024 date "2023-08-29" @default.
• W4386245024 modified "2023-10-18" @default.
• W4386245024 title "Reduced cholecystokinin-expressing interneuron input contributes to disinhibition of the hippocampal CA2 region in a mouse model of temporal lobe epilepsy" @default.
• W4386245024 cites W1492331633 @default.
• W4386245024 cites W1497716686 @default.
• W4386245024 cites W1531000242 @default.
• W4386245024 cites W1541546027 @default.
• W4386245024 cites W1592286181 @default.
• W4386245024 cites W1606104224 @default.
• W4386245024 cites W1846418424 @default.
• W4386245024 cites W1853425391 @default.
• W4386245024 cites W1965625137 @default.
• W4386245024 cites W1970202218 @default.
• W4386245024 cites W1970785187 @default.
• W4386245024 cites W1971630624 @default.
• W4386245024 cites W1973855259 @default.
• W4386245024 cites W1974705547 @default.
• W4386245024 cites W1974809694 @default.
• W4386245024 cites W1976263707 @default.
• W4386245024 cites W1981953070 @default.
• W4386245024 cites W1985249962 @default.
• W4386245024 cites W1988075822 @default.
• W4386245024 cites W1989664355 @default.
• W4386245024 cites W1999766029 @default.
• W4386245024 cites W2005559036 @default.
• W4386245024 cites W2011504521 @default.
• W4386245024 cites W2011747330 @default.
• W4386245024 cites W2014854778 @default.
• W4386245024 cites W2015513895 @default.
• W4386245024 cites W2021258327 @default.
• W4386245024 cites W2021514539 @default.
• W4386245024 cites W2024495291 @default.
• W4386245024 cites W2025488349 @default.
• W4386245024 cites W2031661024 @default.
• W4386245024 cites W2033044289 @default.
• W4386245024 cites W2034382807 @default.
• W4386245024 cites W2041579561 @default.
• W4386245024 cites W2042142350 @default.
• W4386245024 cites W2044975802 @default.
• W4386245024 cites W2051663942 @default.
• W4386245024 cites W2052163800 @default.
• W4386245024 cites W2057195252 @default.
• W4386245024 cites W2058022492 @default.
• W4386245024 cites W2059754952 @default.
• W4386245024 cites W2079239821 @default.
• W4386245024 cites W2079968698 @default.
• W4386245024 cites W2081122323 @default.
• W4386245024 cites W2081727513 @default.
• W4386245024 cites W2082170992 @default.
• W4386245024 cites W2091092254 @default.
• W4386245024 cites W2098371930 @default.
• W4386245024 cites W2102137096 @default.
• W4386245024 cites W2103946141 @default.
• W4386245024 cites W2107420159 @default.
• W4386245024 cites W2113659468 @default.
• W4386245024 cites W2125616660 @default.
• W4386245024 cites W2145617691 @default.
• W4386245024 cites W2159475829 @default.
• W4386245024 cites W2165035001 @default.
• W4386245024 cites W2175272252 @default.
• W4386245024 cites W2229474614 @default.
• W4386245024 cites W2236053794 @default.
• W4386245024 cites W2237341482 @default.
• W4386245024 cites W2259382320 @default.
• W4386245024 cites W2344349459 @default.
• W4386245024 cites W2410908538 @default.
• W4386245024 cites W2467652827 @default.
• W4386245024 cites W2514879313 @default.
• W4386245024 cites W2529600742 @default.
• W4386245024 cites W2530427562 @default.
• W4386245024 cites W2565764659 @default.
• W4386245024 cites W2566914081 @default.
• W4386245024 cites W2591727464 @default.
• W4386245024 cites W2604072435 @default.
• W4386245024 cites W2610785804 @default.
• W4386245024 cites W2613166160 @default.
• W4386245024 cites W2617237563 @default.
• W4386245024 cites W2648952709 @default.
• W4386245024 cites W2735735043 @default.
• W4386245024 cites W2739274933 @default.
• W4386245024 cites W2743764291 @default.
• W4386245024 cites W2743890014 @default.
• W4386245024 cites W2746239521 @default.
• W4386245024 cites W2782520840 @default.
• W4386245024 cites W2788593837 @default.
• W4386245024 cites W2792630499 @default.
• W4386245024 cites W2792702377 @default.
• W4386245024 cites W2810440784 @default.
• W4386245024 cites W2886787141 @default.
• W4386245024 cites W2895687586 @default.

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