Dendritic, backpropagating action potentials (bAPs) facilitate the induction of Hebbian long-term potentiation (LTP).

A-type potassium currents are important determinants of neuronal excitability. In spinal cord dorsal horn neurons, A-type currents are modulated by extracellular signal-regulated kinases (ERKs), which mediate central sensitization during inflammatory pain. Here, we report that Kv4.2 mediates the majority of A-type current in dorsal horn neurons and is a critical site for modulation of neuronal excitability and nociceptive behaviors. Genetic elimination of Kv4.2 reduces A-type currents and increases excitability of dorsal horn neurons, resulting in enhanced sensitivity to tactile and thermal stimuli. Furthermore, ERK-mediated modulation of excitability in dorsal horn neurons and ERK-dependent forms of pain hypersensitivity are absent in Kv4.2(-/-) mice compared to wild-type littermates. Finally, mutational analysis of Kv4.2 indicates that S616 is the functionally relevant ERK phosphorylation site for modulation of Kv4.2-mediated currents in neurons. These results show that Kv4.2 is a downstream target of ERK in spinal cord and plays a crucial role in pain plasticity.

Induced pluripotent stem cells (iPSC) have revolutionized the stem cell field. iPSC are most often produced by using retroviruses. However, the resulting cells may be ill-suited for clinical applications. Many alternative strategies to make iPSC have been developed, but the non-integrating strategies tend to be inefficient, while the integrating strategies involve random integration. Here we report a facile strategy to create murine iPSC that utilizes plasmid DNA and single transfection with sequence-specific recombinases. PhiC31 integrase was used to insert the reprogramming cassette into the genome, producing iPSC. Cre recombinase was then employed for excision of the reprogramming genes. The iPSC were demonstrated to be pluripotent by in vitro and in vivo criteria, both before and after excision of the reprogramming cassette. This strategy is comparable to retroviral approaches in efficiency, but is non-hazardous for the user, simple to perform, and results in non-random integration of a reprogramming cassette that can be readily deleted. We demonstrated the efficiency of this reprogramming and excision strategy in two accessible cell types, fibroblasts and adipose stem cells. This simple strategy produces pluripotent stem cells that have the potential to be used in a clinical setting.

In this hypothesis paper, I propose a three-component set of jointly necessary and sufficient trigger criteria for all cases of involuntary laughter. The theory incorporates concepts from the theory of mind in cognitive science. I then examine the information content of the laughter signal from a game theoretic perspective. I conclude that laughter is a signal of cooperator value as it provides information on the laugher's empathy with the attributed mental states and her sympathy levels for all affected by the laugh-inducing situation. Laughter also indicates what types of mental representations children, autistic people, nonhuman primates and adults possess and can falsify.