Biology subjects

Hirai, H.

Publications and source records attributed to Hirai, H..

22 records · Page 2Linked to original sources

bioRxiv2021

Cortical cell ensemble control of past experience-dependent memory updating

When processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories.

neuroscience↗

bioRxiv2020

Mechanical impact on the head has an antihypertensive effect

Physical exercise is known to be beneficial for various brain functions. However, the mechanisms behind the positive effects of exercise on the brain remain to be elucidated. Here we show that passive head motion in hypertensive rats, which reproduces the mechanical accelerations generated in their heads during moderate-velocity treadmill running, decreases the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM), thereby lowering blood pressure. Passive head motion generates interstitial fluid movement that is estimated to exert shear stress with an average magnitude of <1 Pa on the cells in the rat medulla. Fluid shear stress of a sub-Pa magnitude decreases AT1R expression in cultured astrocytes. In hypertensive rats, inhibition of interstitial fluid movement following hydrogel introduction to the RVLM eliminates the antihypertensive effects of passive head motion and treadmill running. Furthermore, vertically oscillating chair riding by hypertensive adult humans, which reproduces the mechanical accelerations generated in their heads during light jogging or fast walking, lowers their blood pressure. Our findings indicate that moderate mechanical intervention can have antihypertensive effects by modulating the function of RVLM astrocytes through interstitial fluid shear stress. We anticipate that mechanical regulation is responsible for a variety of the positive effects of physical exercise on human health, particularly those related to brain functions.

bioengineering↗

bioRxiv2020

Development and optimization of a high-throughput 3D rat Purkinje neuron culture

Improved understanding of the mechanisms involved in neurodegenerative disease has been hampered by the lack of robust cellular models that faithfully replicate in vivo features. Here, we present a refined protocol for generating age-dependent, well-developed and synaptically active rat Purkinje neurons, responsive to paracrine factors and supporting a 3D cell network. Our model provides high experimental flexibility, high-throughput screening capabilities and reliability to elucidate Purkinje neuron function, communication and neurodegenerative mechanisms.

neuroscience↗

bioRxiv2018

Deletion of class II ARF causes essential tremors through Nav1.6 traffic impairment

ADP-ribosylation factors (ARFs) are a family of small monomeric GTPases consisting of three classes. In the present study, we generated class II ARF-deficient mice (ARF4+/-/ARF5-/-) and found that they exhibited severe movement-associated tremors. Treatment of the mice with propranolol and gabapentin, which alleviate symptoms in patients with essential tremors, similarly reduced the amplitude of the pathologic tremors. In vivo electrophysiological recordings of the ARF4+/-/ARF5-/- mice revealed that they exhibited reduced excitability of their cerebellar Purkinje cells. Immunohistochemical studies revealed that ARF4+/-/ARF5-/- mice exhibit a severe, selective reduction of Nav1.6 proteins that are important for maintaining repetitive action potential firing in the axon initial segments (AISs) of the Purkinje cells. This decrease in Nav1.6 protein expression and the consequent tremors were alleviated by Purkinje cell-specific expression of ARF5. These results indicate that class II ARF mediates the selective trafficking of Nav1.6 to the AISs in cerebellar Purkinje cells, and suggest that the essential tremors can be ascribed to the reduced intrinsic excitability of Purkinje cells, caused by the selective decrease of Nav1.6 proteins in the AISs.

neuroscience↗