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Selective expression of a constitutively active erythropoietin receptor in GABA ergic neurons alters hippocampal network properties without affecting cognition
Author(s) -
Wüstefeld Liane,
Winkler Daniela,
Janc Oliwia A.,
Hassouna Imam,
Ronnenberg Anja,
Ostmeier Katrin,
Müller Michael,
Brose Nils,
Ehrenreich Hannelore,
Wojcik Sonja M.
Publication year - 2016
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.13445
Subject(s) - glutamatergic , neuroscience , hippocampal formation , gabaergic , erythropoietin , long term potentiation , hippocampus , biology , cognition , inhibitory postsynaptic potential , receptor , glutamate receptor , endocrinology , biochemistry
We have previously shown that treatment with erythropoietin ( EPO ) improves cognition in patients with neuropsychiatric disorders as well as in healthy mice, and that transgenic expression of a constitutively active form of the EPO receptor ( cEPOR ) in glutamatergic neurons boosts higher cognitive functions in mice. In the present work, we examined whether selective activation of EPOR signaling in GABA ergic neurons would also modulate cognitive performance. We generated transgenic mice that express cEPOR under the control of the vesicular inhibitory amino acid transporter (Viaat) promoter and subjected them to comprehensive behavioral, cognitive, and electrophysiological analyses. We demonstrate that transgenic expression of cEPOR in GABA ergic neurons alters hippocampal gamma‐oscillations and enhances long‐term potentiation but neither impairs nor improves cognition. To conclude, constitutively active EPOR in GABA ergic neurons changes hippocampal network properties without affecting cognition, which suggests that the effect of EPO on cognition is dominated by its effect on the glutamatergic system.Treatment with EPO improves cognitive performance. We previously demonstrated that this effect is replicated by constitutive autoactivation of cEPOR in glutamatergic neurons. By contrast, cEPOR in GABAergic neurons changes hippocampal network properties but neither impairs nor enhances cognition. Thus, EPO modulates neuronal plasticity, and the cognitive benefits may be mainly attributable to its effect on the glutamatergic system.