PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain

<p>Abstract</p> <p>Background</p> <p>Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC), PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH) mediating persistent pain.</p> <p>Results</p> <p>Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP), at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI) of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs.</p> <p>Conclusions</p> <p>These results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.</p

Tradeoffs between the strength of conformity and number of conformists in variable environments

Organisms often respond to environmental change phenotypically, through learning strategies that enhance fitness in variable and changing conditions. But which strategies should we expect in population exposed to those conditions? We address this question by developing a mathematical model that specifies the consequences of different mixtures of individual and social learning strategies on the frequencies of different cultural variants in temporally and spatially changing environments. Assuming that alternative cultural variants are differently well-adapted to diverse environmental conditions, we are able to evaluate which mixture of learning strategies maximises the mean fitness of the population. We find that, even in rapidly changing environments, a high proportion of the population will always engage in social learning. In those environments, the highest adaptation levels are achieved through relatively high fractions of individual learning and a strong conformist bias. We establish a negative relationship between the proportion of the population learning socially and the strength of conformity operating in a population: strong conformity requires fewer conformists (i.e. larger proportion of individual learning), while many conformists can only be found when conformist transmission is weak. Investigations of cultural diversity show that in frequently changing environments high levels of adaptation require high level of cultural diversity. Finally, we demonstrate how the developed mathematical framework can be applied to time series of usage or occurrence data of cultural traits. Using Approximate Bayesian Computation we are able to infer information about the underlying learning processes that could have produced observed patterns of variation in the dataset

The views are not necessarily those of the Bank of England or the interim Financial Policy Committee.

Peter Zimmerman for comments and contributions. All speeches are available online at www.bankofengland.co.uk/publications/speeches2 1

Planetary health: young academics ask universities to act

International audienc

Planetary health: young academics ask universities to act.

The COVID-19 pandemic has deeply affected societies worldwide, demanding communities to rapidly respond to the health and socioeconomic impacts of the disease. Higher education institutions are uniquely placed to lead a coordinated scientific and educational movement to shape a future that supports recovery from the pandemic and that can lead to improved opportunities in research, education and socio-environmental outcomes. In this commentary, Planetary Health Alliance Campus Ambassadors, a collective of individuals from diverse academic backgrounds representing universities across the world, call upon universities to commit to 5 actions to protect human and planetary health, now and in the future.</div