Infralimbic cortex pyramidal neuron GIRK signaling contributes to regulation of cognitive flexibility but not affect-related behavior in male mice

Anderson, Erik; Demis, Skyler; Wrucke, Benjamin; Engelhardt, Annabel; Hearing, Matthew

doi:10.1016/j.physbeh.2021.113597

Cited by 3 publications

(2 citation statements)

References 104 publications

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“…Here we demonstrate that the consequences of circadian disruption extend to the functional level, reducing information throughput of pyramidal neurons by increasing the threshold for action potential firing, which is critical for communication with other brain regions, such as the hippocampus and amygdala. GIRK channels play a demonstrated role in pyramidal neurons and interneurons throughout the infralimbic and prelimbic cortices 15, 27, 28, 63 . Dynamic changes in GIRK channels underlie stress-induced deficits in cognitive flexibility, and decreased GIRK channel function can impair fear learning, likely through altered communication between the PFC and hippocampus 28, 64 .…”

Section: Discussionmentioning

confidence: 99%

“…Our present results demonstrate that the consequences of circadian desynchronization extend to the cell function level, reducing information throughput of plPFC neurons by increasing the threshold for action potential firing, which is critical for communication with other brain regions, such as the hippocampus and amygdala. GIRK channels play a demonstrated role in pyramidal neurons and interneurons throughout the infralimbic and prelimbic cortices (21)(22)(23)51).…”

Section: Discussionmentioning

confidence: 99%

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Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Roberts

Karatsoreos

2022

Preprint

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Circadian rhythms are ubiquitous in biology, from the molecular to behavioral levels. There is growing interest in understanding the functional implications of circadian oscillations in different cells and systems, including the brain. The prefrontal cortex (PFC) is heavily involved in myriad processes, including working memory, cognition, stress responses, and fear associated behaviors. Many PFC associated behaviors are time-of-day dependent, yet how time-of-day impacts the basic function of neurons in the PFC is not known. Here we use patch-clamp electrophysiology to record from layer 2/3 pyramidal neurons in the prelimbic (pl) PFC of male and female C57BL/6J mice at 4 separate bins of zeitgeber time (ZT): 0-4, 6-10, 12-16, and 18-22. We measured changes in membrane properties, inhibitory and excitatory inputs, ion channel function, and action potential kinetics. We demonstrate that the activity of plPFC neurons, their inhibitory inputs, and action potential dynamics are regulated by time-of-day. Further, we show that in males postsynaptic K+ channels play a central role in mediating these rhythms, suggesting the potential for an intrinsic gating mechanism mediating information throughput. These key discoveries in PFC physiology demonstrate the importance of understanding how daily rhythms contribute to the mechanisms underlying the basic functions of PFC circuitry.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Roberts

Karatsoreos

2022

Preprint

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Neuronal G protein-gated K⁺ channels

Luo

Velasco

Wickman

2022

American Journal of Physiology-Cell Physiology

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G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels exert a critical inhibitory influence on neurons. Neuronal GIRK channels mediate the G protein-dependent, direct/postsynaptic inhibitory effect of many neurotransmitters including γ-aminobutyric acid (GABA), serotonin, dopamine, adenosine, somatostatin, and enkephalin. In addition to their complex regulation by G proteins, neuronal GIRK channel activity is sensitive to PIP2, phosphorylation, regulator of G protein signaling (RGS) proteins, intracellular Na+ and Ca2+, and cholesterol. The application of genetic and viral manipulations in rodent models, together with recent progress in the development of GIRK channel modulators, has increased our understanding of the physiological and behavioral impact of neuronal GIRK channels. Work in rodent models has also revealed that neuronal GIRK channel activity is modified, transiently or persistently, by various stimuli including exposure drugs of abuse, changes in neuronal activity patterns, and aversive experience. A growing body of preclinical and clinical evidence suggests that dysregulation of GIRK channel activity contributes to neurological diseases and disorders. The primary goals of this review are to highlight fundamental principles of neuronal GIRK channel biology, mechanisms of GIRK channel regulation and plasticity, the nascent landscape of GIRK channel pharmacology, and the potential relevance of GIRK channels to the pathophysiology and treatment of neurological diseases and disorders.

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Chronic Cerebral Hypoperfusion-induced Dysregulations of Hyperpolarization- activated Cyclic Nucleotide-gated, KCNQ and G Protein-coupled Inwardly Rectifying Potassium Channels Correlated with Susceptibility and Unsusceptibility to Anxiety Behaviors

Zhou

Lin

et al. 2022

CNR

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Background: Cerebrovascular lesions could induce affective disorders; however, the depression- and anxiety-related symptoms caused by chronic cerebral hypoperfusion (CCH) and the roles of different hyperpolarization-activated cyclic nucleotide-gated (HCN), KCNQ and G protein-coupled inwardly rectifying potassium (GirK) channel subunits in these pathological processes have been poorly elucidated so far. Objective: To investigate the behavioral change and the alteration of HCN, KCNQ, and GirK subunits in amygdale of rats suffered from CCH. Methods: Permanent bilateral occlusion of the common carotid arteries was used to induce CCH. Anxiety and depression levels were assessed by the elevated plus maze test, sucrose preference test and forced swimming test to classify rats as highly anxious or depressive ‘susceptibility’ vs. ‘unsusceptibility’. The expression of brain derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrKB), HCN1/2, KCNQ2/3, and GirK1/2/3 were quantified by Western blotting. Results: The mainly emotional change caused by 4 weeks of CCH is likely to be anxiety-like behavior (50%), accompanied by a down-regulation of BDNF and TrKB expression in amygdale. The increase of HCN1 and decrease of KCNQ3 expression in amygdale may be factors to blame for anxiety-like symptom caused by CCH, and the increase of KCNQ2 and Girk1 expression in amygdale may play a role in resilience to the anxiety induced by CCH. Conclusion: The different subunits of HCN, KCNQ and GirK channels in amygdale may contribute to distinct response to aversive stimuli or stress induced by CCH that evokes divergent influence on anxiety-like behavior in rats.

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Infralimbic cortex pyramidal neuron GIRK signaling contributes to regulation of cognitive flexibility but not affect-related behavior in male mice

Cited by 3 publications

References 104 publications

Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Neuronal G protein-gated K⁺ channels

Chronic Cerebral Hypoperfusion-induced Dysregulations of Hyperpolarization- activated Cyclic Nucleotide-gated, KCNQ and G Protein-coupled Inwardly Rectifying Potassium Channels Correlated with Susceptibility and Unsusceptibility to Anxiety Behaviors

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Infralimbic cortex pyramidal neuron GIRK signaling contributes to regulation of cognitive flexibility but not affect-related behavior in male mice

Cited by 3 publications

References 104 publications

Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Circadian desynchronization attenuates information throughput of prefrontal cortex pyramidal neurons in mice

Neuronal G protein-gated K+ channels

Chronic Cerebral Hypoperfusion-induced Dysregulations of Hyperpolarization- activated Cyclic Nucleotide-gated, KCNQ and G Protein-coupled Inwardly Rectifying Potassium Channels Correlated with Susceptibility and Unsusceptibility to Anxiety Behaviors

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Neuronal G protein-gated K⁺ channels