Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome.

Abstract:

:GABAergic dysfunction is implicated in hippocampal deficits of the Ts65Dn mouse model of Down syndrome (DS). Since Ts65Dn mice overexpress G-protein coupled inward-rectifying potassium (GIRK2) containing channels, we sought to evaluate whether increased GABAergic function disrupts the functioning of hippocampal circuitry. After confirming that GABA(B)/GIRK current density is significantly elevated in Ts65Dn CA1 pyramidal neurons, we compared monosynaptic inhibitory inputs in CA1 pyramidal neurons in response to proximal (stratum radiatum; SR) and distal (stratum lacunosum moleculare; SLM) stimulation of diploid and Ts65Dn acute hippocampal slices. Synaptic GABA(B) and GABA(A) mediated currents evoked by SR stimulation were generally unaffected in Ts65Dn CA1 neurons. However, the GABA(B)/GABA(A) ratios evoked by stimulation within the SLM of Ts65Dn hippocampus were significantly larger in magnitude, consistent with increased GABA(B)/GIRK currents after SLM stimulation. These results indicate that GIRK overexpression in Ts65Dn has functional consequences which affect the balance between GABA(B) and GABA(A) inhibition of CA1 pyramidal neurons, most likely in a pathway specific manner, and may contribute to cognitive deficits reported in these mice.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Best TK,Cramer NP,Chakrabarti L,Haydar TF,Galdzicki Z

doi

10.1016/j.expneurol.2011.11.033

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

749-57

issue

2

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(11)00437-7

journal_volume

233

pub_type

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