G-protein-gated inwardly rectifying potassium (kir3/ girk) channels govern synaptic plasticity that supports hippocampal-dependent cognitive functions in male mice

Souhail Djebari, Guillermo Iborra-Lázaro, Sara Temprano-Carazo, Irene Sánchez-Rodríguez, Mauricio O. Nava-Mesa, Alejandro Múnera, Agnès Gruart, José M. Delgado-García, Lydia Jiménez-Díaz, Juan D. Navarro-López

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The G-protein-gated inwardly rectifying potassium (Kir3/GIRK) channel is the effector of many G-protein-coupled receptors (GPCRs). Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer's and Parkinson's diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. In the hippocampus, GIRK channels decrease excitability of the cells and contribute to resting membrane potential and inhibitory neurotransmission. Here, to elucidate the role of GIRK channels activity in the maintenance of hippocampal-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined in C57BL/6 male mice. For that purpose, GIRK activity in the dorsal hippocampus CA32CA1 synapse was pharmacologically modulated by two drugs: ML297, a GIRK channel opener, and Tertiapin-Q (TQ), a GIRK channel blocker. Ex vivo, using dorsal hippocampal slices, we studied the effect of pharmacological GIRK modulation on synaptic plasticity processes induced in CA1 by Schaffer collateral stimulation. In vivo, we performed acute intracerebroventricular (i.c.v.) injections of the two GIRK modulators to study their contribution to electrophysiological properties and synaptic plasticity of dorsal hippocampal CA32CA1 synapse, and to learning and memory capabilities during hippocampal-dependent tasks. We found that pharmacological disruption of GIRK channel activity by i.c.v. injections, causing either function gain or function loss, induced learning and memory deficits by a mechanism involving neural excitability impairments and alterations in the induction and maintenance of longterm synaptic plasticity processes. These results support the contention that an accurate control of GIRK activity must take place in the hippocampus to sustain cognitive functions.

Translated title of the contributionCanales de potasio rectificadores de entrada gobierna la plasticidad sinaptica que soporta las funciones cognitivas dependientes del hipocampo en ratones macho.
Original languageEnglish (US)
Pages (from-to)7086-7102
Number of pages17
JournalJournal of Neuroscience
Issue number33
StatePublished - Aug 18 2021

All Science Journal Classification (ASJC) codes

  • General Neuroscience


Dive into the research topics of 'G-protein-gated inwardly rectifying potassium (kir3/ girk) channels govern synaptic plasticity that supports hippocampal-dependent cognitive functions in male mice'. Together they form a unique fingerprint.

Cite this