Neurons and Cognition (q-bio.NC)

Abstract: Major depressive disorder is a widespread mood disorder. One of the most debilitating symptoms patients often experience is cognitive impairment. Recent findings suggest that inflammation is associated with depression and impaired cognition. Pro-inflammatory cytokines are elevated in the blood of depressed patients and impair learning and memory processes, suggesting that an anti-inflammatory approach might be beneficial for both depression and cognition. Utilizing the learned helplessness paradigm, we first established a mouse model of depression in which learning and memory are impaired. We found that learned helplessness (LH) impaired novel object recognition (NOR) and spatial working memory. LH mice also exhibited reduced hippocampal dendritic spine density and increased microglial activation compared to non-shocked (NS) mice or mice that were subjected to the learned helpless paradigm but did not exhibit learned helplessness (non-learned helpless, or NLH). These effects were mediated by microglia, as treatment with PLX5622, which depletes microglia and macrophages, restored learning and memory and hippocampal dendritic spine density in LH mice. However, PLX5622 also impaired learning and memory and reduced hippocampal dendritic spine density in NLH mice, suggesting that microglia in NLH mice are involved in the production of molecules that promote learning and memory. We found that microglial interleukin (IL)-10 levels were reduced in LH mice and IL-10 administration was sufficient to restore NOR, spatial working memory, and hippocampal dendritic spine density in LH mice, and in NLH mice treated with PLX5622, consistent with a pro-cognitive role for IL-10. Altogether, these data demonstrate the critical role of IL-10 in promoting learning and memory after learned helplessness.

Abstract: The evolution of the human mind through natural selection mandates that our conscious experiences are causally potent in order to leave a tangible impact upon the surrounding physical world. Any attempt to construct a functional theory of the conscious mind within the framework of classical physics, however, inevitably leads to causally impotent conscious experiences in direct contradiction to evolution theory. Here, we derive several rigorous theorems that identify the origin of the latter impasse in the mathematical properties of ordinary differential equations employed in combination with the alleged functional production of the mind by the brain. Then, we demonstrate that a mind--brain theory consistent with causally potent conscious experiences is provided by modern quantum physics, in which the unobservable conscious mind is reductively identified with the quantum state of the brain and the observable brain is constructed by the physical measurement of quantum brain observables. The resulting quantum stochastic dynamics obtained from sequential quantum measurements of the brain is governed by stochastic differential equations, which permit genuine free will exercised through sequential conscious choices of future courses of action. Thus, quantum reductionism provides a solid theoretical foundation for the causal potency of consciousness, free will and cultural transmission.