z-logo
Premium
Age‐dependent loss of parvalbumin‐expressing hippocampal interneurons in mice deficient in CHL 1, a mental retardation and schizophrenia susceptibility gene
Author(s) -
Schmalbach Barbara,
Lepsveridze Eka,
Djogo Nevena,
Papashvili Giorgi,
Kuang Fang,
Leshchyns'ka Iryna,
Sytnyk Vladimir,
Nikonenko Alexander G.,
Dityatev Alexander,
Jakovcevski Igor,
Schachner Melitta
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13284
Subject(s) - parvalbumin , hippocampal formation , excitatory postsynaptic potential , neuroscience , biology , inhibitory postsynaptic potential , synaptic plasticity , interneuron , hippocampus , long term potentiation , schizophrenia (object oriented programming) , endocrinology , psychology , receptor , genetics , psychiatry
In humans, deletions/mutations in the CHL 1/ CALL gene are associated with mental retardation and schizophrenia. Juvenile CHL 1‐deficient ( CHL 1 −/− ) mice have been shown to display abnormally high numbers of parvalbumin‐expressing ( PV + ) hippocampal interneurons and, as adults, display behavioral traits observed in neuropsychiatric disorders. Here, we addressed the question whether inhibitory interneurons and synaptic plasticity in the CHL 1 −/− mouse are affected during brain maturation and in adulthood. We found that hippocampal, but not neocortical, PV + interneurons were reduced with age in CHL 1 −/− mice, from a surplus of +27% at 1 month to a deficit of ‐20% in adulthood compared with wild‐type littermates. This loss occurred during brain maturation, correlating with microgliosis and enhanced interleukin‐6 expression. In parallel with the loss of PV + interneurons, the inhibitory input to adult CA 1 pyramidal cells was reduced and a deficit in short‐ and long‐term potentiation developed at CA 3– CA 1 excitatory synapses between 2 and 9 months of age in CHL 1 −/− mice. This deficit could be abrogated by a GABA A receptor agonist. We propose that region‐specific aberrant GABA ergic synaptic connectivity resulting from the mutation and a subsequently enhanced synaptic elimination during brain maturation lead to microgliosis, increase in pro‐inflammatory cytokine levels, loss of interneurons, and impaired synaptic plasticity.Close homolog of L1‐deficient ( CHL1 −/− ) mice have abnormally high numbers of parvalbumin (PV)‐expressing hippocampal interneurons in juvenile animals, but in adult animals a loss of these cells is observed. This loss correlates with an increased density of microglia (M), enhanced interleukin‐6 (IL6) production and a deficit in short‐ and long‐term potentiation at CA3–CA1 excitatory synapses. Furthermore, adult CHL1 −/− mice display behavioral traits similar to those observed in neuropsychiatric disorders of humans.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here