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Hamada, H. T.

Publications and source records attributed to Hamada, H. T..

3 recordsLinked to original sources

Neural correlates of phenomenological attitude toward perceptual experience

Phenomenology is one of the most promising approaches to study conscious experience. It holds that a rigorous study of conscious experience requires a transition in the subject from the "natural attitude" (NA) to the "phenomenological attitude" (PA). NA describes our ordinary stance, in which our attention is directed at external objects and events. PA is a distinctive, reflective stance in which our attention is directed at our conscious experience itself. Despite its theoretical importance in philosophy and science of consciousness, the neural mechanisms underlying PA remain unknown. To clarify this point, we developed a novel behavioral task in which participants alternate between NA and PA in relation to their stimulus-evoked subjective experiences. Participants are presented with two sentences and requested to identify the one that best captures their experience. These sentences are designed to induce either NA or PA. We found that participants had lower error rates but slower reaction times in the PA condition compared to the NA condition, suggesting a difference beyond task difficulty. Using fMRI, we also found that multivoxel activation patterns in the premotor cortex, posterior parietal cortex, supplementary motor area, and cerebellum successfully classified the task conditions. Furthermore, the activation strength in these regions was lower in the PA condition, indicating that PA depends on neural processes that suppress action-related information. These findings provide the first evidence for the neural signature of PA, contributing to a better understanding of phenomenological method and its underlying neural mechanisms. Significance statementPhenomenology is one of the most promising approaches to study conscious experience. A key step is a transition from the natural attitude (NA)--where our attention is directed at external objects and events--to the phenomenological attitude (PA)--where our attention is directed toward our conscious experience itself. However, the neural processes underlying PA remain unclear. This study aimed to clarify this point by analyzing fMRI signals measured during a cognitive task that forced participants to repeatedly alternate between NA and PA. We observed that multiple action-related brain regions exhibited different activation patterns between NA and PA. Our findings provide the first neuroscientific evidence that illuminates the core process of the phenomenological method.

neuroscience↗

Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward network

Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.

neuroscience↗

TOB is an effector of the hippocampus-mediated acute stress response

Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, (TOB1) is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in the brains stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study suggests that TOB serves as an important modulator in hippocampal stress signaling machinery. In summary, we show a molecular pathway and neural circuit mechanism by which TOB deletion contributes to expression of pathological stress-related behavior.

neuroscience↗