Transient potassium current channels (I A channels), which are expressed in most brain areas, have a central role in modulating feedforward and feedback inhibition along the dendroaxonic axis. Loss of the modulatory channels is tightly associated with a number of brain diseases such as Alzheimer’s disease, epilepsy, fragile X syndrome (FXS), Parkinson’s disease, chronic pain, tinnitus, and ataxia. However, the functional significance of I A channels in these diseases has so far been underestimated. In this review, we discuss the distribution and function of I A channels. Particularly, we posit that downregulation of I A channels results in neuronal (mostly dendritic) hyperexcitability accompanied by the imbalanced excitation and inhibition ratio in the brain’s networks, eventually causing the brain diseases. Finally, we propose a potential therapeutic target: the enhanced action of I A channels to counteract Ca 2+ -permeable channels including NMDA receptors could be harnessed to restore dendritic excitability, leading to a balanced neuronal state.

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The hippocampus is regarded as a cognition hub, particularly for learning and memory. Previously, neuronal mechanisms underlying various cognitive functions are delineated with the lamellar hippocampal circuitry, dentate gyrus-CA3 or CA2-CA1, within the transverse plane. More recently, interlamellar (often referred to as longitudinal) projections have received intensive attention to help understand signal convergence and divergence in cognition and behavior. Signal propagation along the longitudinal axis is evidenced by axonal arborization patterns and synaptic responses to electro-and photo-stimulation, further demonstrating that information flow is more enriched in the longitudinal plane than the transverse plane. Here, we review the significance of longitudinal connections for cognition, discuss a putative circuit mechanism of place coding, and suggest the reconceptualization of the hippocampal circuitry.

Declining global DNA methylation and cognitive impairment are reported to occur in the normal aging process. It is not known if DNA methylation plays a role in the efficacy of memory-enhancing therapies. In this study, aged animals were administered prelimbic cortical deep brain stimulation (PrL DBS) and/or Lmethionine (MET) treatment. We found that PrL DBS and MET (MET-PrL DBS) co-administration resulted in hippocampal-dependent spatial memory enhancements in aged animals. Molecular data suggested MET-PrL DBS induced DNA methyltransferase DNMT3a-dependent methylation, robust synergistic upregulation of neuroplasticity-related genes, and simultaneous inhibition of the memory-suppressing gene calcineurin in the hippocampus. We further found that MET-PrL DBS also activated the PKA-CaMKIIα-BDNF pathway, increased hippocampal neurogenesis, and enhanced dopaminergic and serotonergic neurotransmission. We next inhibited the activity of DNA methyltransferase (DNMT) by RG108 infusion in the hippocampus of young animals to establish a causal relationship between DNMT activity and the effects of PrL DBS. Hippocampal DNMT inhibition in young animals was sufficient to recapitulate the behavioral deficits observed in aged animals and abolished the memory-enhancing and molecular effects of PrL DBS. Our findings implicate hippocampal DNMT as a therapeutic target for PrL DBS and pave way for the potential use of non-invasive neuromodulation modalities against dementia.

This paper reports, for the first time, the results of a systematic experimental investigation of solder paste viscosity on the porosity and mechanical properties of surface mount solder joints. By means of X-ray radiography, it is generally observed that solder joints have greater porosity area fraction for higher solder paste viscosity. With increasing viscosity from 35.3-213 Pa.s, the porosity area fraction varies from 3.0-9.9%, respectively. Thermogravitational analyses on these solder pastes were performed to explain the observed phenomena. It is found that the solder paste with lower viscosity range has a larger evaporation rate of organics than those with higher viscosity range before metal alloys melting, but a smaller rate after metal alloys melting. Shear test results demonstrate that solder joints fabricated with lower viscosity solder paste have higher shear strength by up to 30% (increased from 35.3-46.3 MPa for viscosity change from 213-35.2 Pa.s, respectively).