Biology subjects

Murase, S.

Publications and source records attributed to Murase, S..

8 recordsLinked to original sources

bioRxiv2026

Visual deprivation in adulthood engages presynaptic plasticity of thalamocortical synapses

Synaptic plasticity between neurons in first order thalamus and layer 4 cortex is greatest during an early postnatal critical period and was thought to decrease irreversibly with age. However, here we show that robust and reversible plasticity can be induced in adult mice at synapses between dLGN axons and visual cortex layer 4 neurons by prolonged dark exposure (DE) and light reintroduction (LRx). Unexpectedly, the experience-dependent change in synaptic strength was mediated by a change in presynaptic structure, organization and function. DE/LRx declusters/clusters synaptic vesicles and reorganizes presynaptic molecular geometry. Furthermore, DE/LRx decreases/increases visually-evoked and spontaneous calcium signaling and neurotransmitter release probability in dLGN axonal boutons. The presynaptic plasticity mechanism described here has a high threshold for engagement which would allow maintenance of synapse stability across a wide activity range, and reactivation of thalamocortical plasticity in extraordinary conditions.

neuroscience↗

bioRxiv2024

Adult visual deprivation engages associative, presynaptic plasticity of thalamic input to cortex

Age constrains plasticity at inputs from first order thalamic nuclei to the cortex, endowing stability to ascending, feed-forward projections. However, here we show that prolonged visual deprivation can induce robust and reversible plasticity at thalamocortical synapses in layer 4 pyramidal neurons in the adult mouse primary visual cortex. The plasticity engaged by prolonged visual deprivation is non-homeostatic and mediated by changes in presynaptic function.

neuroscience↗

bioRxiv2022

Application of Passive Head Motion to Generate Defined Accelerations at the Heads of Rodents

Exercise is widely recognized as effective for various diseases and physical disorders, including those related to brain dysfunction. However, molecular mechanisms behind the beneficial effects of exercise are poorly understood. Many physical workouts, particularly those classified as aerobic exercises such as jogging and walking, produce impulsive forces at the time of foot contact with the ground. Therefore, it was speculated that mechanical impact might be implicated in how exercise contributes to organismal homeostasis. For testing this hypothesis on the brain, a custom-designed passive head motion (hereafter referred to as PHM) system was developed that can generate vertical accelerations with controlled and defined magnitudes and modes and reproduce mechanical stimulation that might be applied to the heads of rodents during treadmill running at moderate velocities, a typical intervention to test the effects of exercise in animals. By using this system, it was demonstrated that PHM recapitulates the serotonin (5-hydroxytryptamine, hereafter referred to as 5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) neurons of mice. This work provides detailed protocols for applying PHM and measuring its resultant mechanical accelerations at rodents heads. SUMMARYThe present protocol describes a custom-designed passive head motion system, which reproduces mechanical accelerations at rodents heads generated during their treadmill running at moderate velocities. It allows dissecting mechanical factors/elements from the beneficial effects of physical exercise.

bioengineering↗

bioRxiv2021

All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity

Disinhibition is an obligatory initial step in the remodeling of cortical circuits by sensory experience. Our investigation on disinhibitory mechanisms in the classical model of ocular dominance plasticity uncovered an unexpected novel form of experience-dependent circuit plasticity. In layer 2/3 of mouse visual cortex monocular deprivation triggers a complete, "all-or-none", elimination of connections from pyramidal cells onto nearby parvalbumin-positive interneurons (PyrPV). This circuit plasticity is unique as it is transient, local and discrete. It lasts only one day, and it does not manifest as widespread changes in synaptic strength, rather, only about half of local connections are lost and the remaining ones are not affected in strength. Mechanistically, the deprivation-induced loss of PyrPV is contingent on a reduction of the protein neuropentraxin2 (NPTX2). Functionally, the loss of PyrPV is absolutely necessary for ODP. We surmise, therefore, that this "all-or-none" loss of local PyrPV circuitry gates experience-dependent cortical plasticity.

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↗

bioRxiv2019

Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular substrates by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and degradation of ECM in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. This homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.

neuroscience↗

bioRxiv2019

Regulation of expression site and generalizability of experience-dependent plasticity in visual cortex

The experience-dependent decrease in stimulus detection thresholds that underly perceptual learning can be induced by repetitive exposure to a visual stimulus. Robust stimulus-selective potentiation of visual responses is induced in the primary mouse visual cortex by repetitive low frequency visual stimulation (LFVS). How the parameters of the repetitive visual stimulus impact the site and specificity of this experience-dependent plasticity is currently a subject of debate. Here we demonstrate that the stimulus selective response potentiation induced by repetitive low frequency (1 Hz) stimulation, which is typically limited to layer 4, shifts to superficial layers following manipulations that enhance plasticity in primary visual cortex. In contrast, repetitive high frequency (10 Hz) visual stimulation induces response potentiation that is expressed in layers 4 and 5/6, and generalizes to novel visual stimuli. Repetitive visual stimulation also induces changes in the magnitude and distribution of oscillatory activity in primary visual cortex, however changes in oscillatory power do not predict the locus or specificity of response potentiation. Instead we find that robust response potentiation is induced by visual stimulation that resets the phase of ongoing gamma oscillations. Furthermore, high frequency, but not low frequency, repetitive visual stimulation entrains oscillatory rhythms with enhanced sensitivity to phase reset, such that familiar and novel visual stimuli induce similar visual response potentiation.

neuroscience↗

bioRxiv2019

Complement- and inflammasome-mediated autoinflammation-paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by complement-mediated hemolysis and thrombosis, and bone marrow failure. Affected cells harbor somatic mutation in X-linked PIGA gene, essential for the initial step in glycosylphosphatidylinositol (GPI) biosynthesis. Loss of GPI biosynthesis results in defective cell-surface expression of GPI-anchored complement regulators CD59 and DAF. The affected stem cells generate many abnormal blood cells after clonal expansion, which occurs under bone marrow failure. Here, we report the mechanistic basis of a disease entity, autoinflammation-paroxysmal nocturnal hemoglobinuria (AIF-PNH), caused by germline mutation plus somatic loss of PIGT on chromosome 20q. A region containing maternally imprinted genes implicated in clonal expansion in 20q-myeloproliferative syndromes was lost together with normal PIGT from paternal chromosome 20. Taking these findings together with a lack of bone marrow failure, the mechanisms of clonal expansion in AIF-PNH appear to differ from those in PNH. AIF-PNH is characterized by intravascular hemolysis and recurrent autoinflammation, such as urticaria, arthralgia, fever and aseptic meningitis. Consistent with PIGTs essential role in synthesized GPIs attachment to precursor proteins, non-protein-linked free GPIs appeared on the surface of PIGT-defective cells. PIGT-defective THP-1 cells accumulated higher levels of C3 fragments and C5b-9 complexes, and secreted more IL-1{beta} than PIGA-defective cells after activation of the complement alternative pathway. IL-1{beta} secretion was dependent upon C5b-9 complexes, accounting for the effectiveness of the anti-C5 drug eculizumab for both intravascular hemolysis and autoinflammation. These results suggest that free GPIs enhance complement activation and inflammasome-mediated IL-1{beta} secretion.

immunology↗