Kaoru Takakusaki’s research while affiliated with Asahikawa Medical University and other places

The evolution of brain-expressed genes is notably slower than that of genes expressed in other tissues, a phenomenon likely due to high-level functional constraints. One such constraint might be the integration of information by neuron assemblies, enhancing environmental adaptability. This study explores the physiological mechanisms of information integration in neurons through three types of synchronization: chemical, electromagnetic, and quantum. Chemical synchronization involves the diffuse release of neurotransmitters like dopamine and acetylcholine, causing transmission delays of several milliseconds. Electromagnetic synchronization encompasses action potentials, electrical gap junctions, and ephaptic coupling. Electrical gap junctions enable rapid synchronization within cortical GABAergic networks, while ephaptic coupling allows structures like axon bundles to synchronize through extracellular electromagnetic fields, surpassing the speed of chemical processes. Quantum synchronization is hypothesized to involve ion coherence during ion channel passage and the entanglement of photons within the myelin sheath. Unlike the finite-time synchronization seen in chemical and electromagnetic processes, quantum entanglement provides instantaneous non-local coherence states. Neurons might have evolved from slower chemical diffusion to rapid temporal synchronization, with ion passage through gap junctions within cortical GABAergic networks potentially facilitating both fast gamma band synchronization and quantum coherence. This mini-review compiles literature on these three synchronization types, offering new insights into the physiological mechanisms that address the binding problem in neuron assemblies.

The Earth’s abundance of iron has played a crucial role in both generating its geomagnetic field and contributing to the development of early life. In ancient oceans, iron ions, particularly around deep-sea hydrothermal vents, might have catalyzed the formation of macromolecules, leading to the emergence of life and the Last Universal Common Ancestor. Iron continued to influence catalysis, metabolism, and molecular evolution, resulting in the creation of magnetosome gene clusters in magnetotactic bacteria, which enabled these unicellular organisms to detect geomagnetic field. Although humans lack a clearly identified organ for geomagnetic sensing, many life forms have adapted to geomagnetic field—even in deep-sea environments—through mechanisms beyond the conventional five senses. Research indicates that zebrafish hindbrains are sensitive to magnetic fields, the semicircular canals of pigeons respond to weak potential changes through electromagnetic induction, and human brainwaves respond to magnetic fields in darkness. This suggests that the trigeminal brainstem nucleus and vestibular nuclei, which integrate multimodal magnetic information, might play a role in geomagnetic processing. From iron-based metabolic systems to magnetic sensing in neurons, the evolution of life reflects ongoing adaptation to geomagnetic field. However, since magnetite-activated, torque-based ion channels within cell membranes have not yet been identified, specialized sensory structures like the semicircular canals might still be necessary for detecting geomagnetic orientation. This mini-review explores the evolution of life from Earth’s formation to light-independent human magnetoreception, examining both the magnetite hypothesis and the electromagnetic induction hypothesis as potential mechanisms for human geomagnetic detection.

Background An impaired intestinal barrier with the activation of corticotropin‐releasing factor (CRF), Toll‐like receptor 4 (TLR4), and proinflammatory cytokine signaling, resulting in visceral hypersensitivity, is a crucial aspect of irritable bowel syndrome (IBS). The gut exhibits abundant expression of neurotensin; however, its role in the pathophysiology of IBS remains uncertain. This study aimed to clarify the effects of PD149163, a specific agonist for neurotensin receptor 1 (NTR1), on visceral sensation and gut barrier in rat IBS models. Methods The visceral pain threshold in response to colonic balloon distention was electrophysiologically determined by monitoring abdominal muscle contractions, while colonic permeability was measured by quantifying absorbed Evans blue in colonic tissue in vivo in adult male Sprague–Dawley rats. We employed the rat IBS models, i.e., lipopolysaccharide (LPS)‐ and CRF‐induced visceral hypersensitivity and colonic hyperpermeability, and explored the effects of PD149163. Key Results Intraperitoneal PD149163 (160, 240, 320 μg kg⁻¹) prevented LPS (1 mg kg⁻¹, subcutaneously)‐induced visceral hypersensitivity and colonic hyperpermeability dose‐dependently. It also prevented the gastrointestinal changes induced by CRF (50 μg kg⁻¹, intraperitoneally). Peripheral atropine, bicuculline (a GABAA receptor antagonist), sulpiride (a dopamine D2 receptor antagonist), astressin2‐B (a CRF receptor subtype 2 [CRF2] antagonist), and intracisternal SB‐334867 (an orexin 1 receptor antagonist) reversed these effects of PD149163 in the LPS model. Conclusions and Inferences PD149163 demonstrated an improvement in visceral hypersensitivity and colonic hyperpermeability in rat IBS models through the dopamine D2, GABAA, orexin, CRF2, and cholinergic pathways. Activation of NTR1 may modulate these gastrointestinal changes, helping to alleviate IBS symptoms.

Bipedal gait involves moving the body while maintaining an upright posture under gravity. Throughout vertebrate evolution and postnatal development, humans acquired antigravity functions that allow one to achieve biped gait. While walking, our attention is focused on purposeful, intentional movements such as dexterous arm-hand finger movements or searching for the target. On the other hand, postural control comes to our awareness only when we need to alter gait patterns, such as facing demanding conditions. Nonetheless, our body and brain control gait so as not to fall by anticipatorily adjusting posture that optimally achieves multi-tasks consisting of purposeful movements and walking. Accordingly, we have developed the working hypothesis that postural control is achieved by plans and programs that accomplish purposeful actions. Key questions to verify this hypothesis are (1) how higher brain functions brought about by evolution enabled us to acquire a bipedal standing posture that resists gravity and (2) how the frontal cortex, the most developed neocortical area, enabled us to acquire multi-tasks consisting of gait and intentional movements. We postulate that the frontoparietal networks that contribute to planning and programming based on cognitive information and corticofugal pathways that issue command signals to the subcortical structures, particularly the brainstem and spinal cord in which core systems of posture and gait control exist, play central roles in solving these questions. These mechanisms may be declined in older adults and impaired in patients with degenerative neurological disorders, resulting in posture-gait disturbance such as freezing of gait (FOG) and falling.