Background Cognitive dysfunction occurs in many debilitating conditions including Alzheimer’s disease, Down syndrome, schizophrenia, and mood disorders. The dorsal hippocampus is a critical locus of cognitive processes linked to spatial and contextual learning. G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, which mediate the postsynaptic inhibitory effect of many neurotransmitters, have been implicated in hippocampal-dependent cognition. Available evidence, however, derives primarily from constitutive gain-of-function models that lack cellular specificity. Methods We used constitutive and neuron-specific gene ablation models targeting an integral subunit of neuronal GIRK channels (GIRK2) to probe the impact of GIRK channels on associative learning and memory. Results Constitutive Girk2−/− mice exhibited a striking deficit in hippocampal-dependent (contextual) and hippocampal-independent (cue) fear conditioning. Mice lacking GIRK2 in GABA neurons (GAD-Cre:Girk2flox/flox mice) exhibited a clear deficit in GIRK-dependent signaling in dorsal hippocampal GABA neurons, but no evident behavioral phenotype. Mice lacking GIRK2 in forebrain pyramidal neurons (CaMKII-Cre(+):Girk2flox/flox mice) exhibited diminished GIRK-dependent signaling in dorsal, but not ventral, hippocampal pyramidal neurons. CaMKII-Cre(+):Girk2flox/flox mice also displayed a selective impairment in contextual fear conditioning, as both cue-fear and spatial learning were intact in these mice. Finally, loss of GIRK2 in forebrain pyramidal neurons correlated with enhanced long-term depression and blunted depotentiation of long-term potentiation at the Schaffer collateral/CA1 synapse in the dorsal hippocampus. Conclusions Our data suggest that GIRK channels in dorsal hippocampal pyramidal neurons are necessary for normal learning involving aversive stimuli, and support the contention that dysregulation of GIRK-dependent signaling may underlie cognitive dysfunction in some disorders.

The inclusion of community voices in research is important. Over the years, research training programs have continued to emphasize that engagement with communities at the focus of research can promote thoughtful, sensitive designs ( Rivera et al., 2004 ). In this paper, we discuss a method for youth participation in the research process. In an attempt to move beyond “staged and superficial” participation in gathering youth perspectives, we advocate for including co-researchers in the development and modification of fundamental aspects of the research process, from data analysis to the development of additional research questions and collection methods ( Guishard & Tuck, 2013 ). In the course of a study designed to enroll middle school students in participatory co-design sessions ( Cahill, 2007 ) to aid in the development of educational technologies, it became apparent that our youth participants, as co-researchers, could also aid in the development, analysis, and coding of anonymized interview transcripts; development of themes; and creation of models for behaviors found in the transcripts ( Docan-Morgan, 2010 ; Luchtenberg et al., 2020 ). Thus, this paper presents a practical example of a co-research process that includes youth participants, with an emphasis on training in qualitative coding and the fundamentals of research design.

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