Masato Tsuji

Heartbeat and behavior are tightly coordinated during defensive states, yet the neuronal mechanisms linking threat processing to cardiac modulation—and the potential contribution of cardiac dynamics to behavioral output—remain poorly understood. Here, using simultaneous recordings of heartbeat and behavior in tethered Drosophila , we show that mechanical threat triggers locomotion together with rapid cardiac deceleration. We identify two pairs of dopaminergic neurons, termed DA-WED neurons, that mediate this cardiac response. Silencing these neurons markedly attenuates threat-induced cardiac deceleration, whereas optogenetic activation induces cardiac deceleration in the absence of threat. Two-photon calcium imaging further shows that DA-WED neurons are activated by mechanical threat, and manipulating their activity bidirectionally modulates threat-induced locomotion. Linking cardiac dynamics to behavior, direct optogenetic manipulation of cardiomyocytes that quantitatively reproduces threat-evoked cardiac deceleration is accompanied by increased locomotion. Together, these results identify a dopaminergic descending pathway that links threat processing to cardiac modulation and suggest that cardiac dynamics may contribute to shaping defensive behavior.

Heartbeat and behavior are tightly coordinated during defensive states, yet the neuronal mechanisms linking threat processing to cardiac modulation—and the potential contribution of cardiac dynamics to behavioral output—remain poorly understood. Here we show in Drosophila that mechanical threat triggers locomotion together with cardiac deceleration. We identify two pairs of dopaminergic neurons, termed DA-WED neurons, that mediate this cardiac response: silencing these neurons markedly attenuates threat-induced cardiac deceleration, whereas optogenetic activation induces cardiac deceleration in the absence of threat. Calcium imaging further shows that DA-WED neurons are activated by mechanical threat. Linking cardiac dynamics to behavior, direct optogenetic manipulation of cardiomyocytes that quantitatively reproduces threat-evoked cardiac deceleration is accompanied by increased locomotion. Together, these results identify a dopaminergic descending pathway that links threat processing to cardiac modulation and suggest that cardiac dynamics may contribute to shaping defensive behavior.

Heartbeat and behavior are tightly coordinated during defensive states, yet the neuronal mechanisms linking threat processing to cardiac modulation—and the potential contribution of cardiac dynamics to behavioral output—remain poorly understood. Here we show in Drosophila that mechanical threat triggers locomotion together with cardiac deceleration. We identify two dopaminergic neurons, termed DA-WED neurons, that mediate this cardiac response: silencing these neurons markedly attenuates threat-induced cardiac deceleration, whereas optogenetic activation induces cardiac deceleration in the absence of threat. Calcium imaging further shows that DA-WED neurons are activated by mechanical threat. Linking cardiac dynamics to behavior, direct optogenetic manipulation of cardiomyocytes that quantitatively reproduces threat-evoked cardiac deceleration is accompanied by increased locomotion. Together, these results identify a dopaminergic descending pathway that links threat processing to cardiac modulation and suggest that cardiac dynamics may contribute to shaping defensive behavior.

Heartbeat and behavior are tightly coordinated during defensive states, yet the neuronal mechanisms linking threat processing to cardiac modulation—and the potential contribution of cardiac dynamics to behavioral output—remain poorly understood. Here we show in Drosophila that mechanical threat triggers locomotion together with cardiac deceleration. We identify two dopaminergic neurons, termed DA-WED neurons, that mediate this cardiac response: silencing these neurons markedly attenuates threat-induced cardiac deceleration, whereas optogenetic activation induces cardiac deceleration in the absence of threat. Calcium imaging further shows that DA-WED neurons are activated by mechanical threat. Linking cardiac dynamics to behavior, direct optogenetic manipulation of cardiomyocytes that quantitatively reproduces threat-evoked cardiac deceleration is accompanied by increased locomotion. Together, these results identify a dopaminergic descending pathway that links threat processing to cardiac modulation and suggest that cardiac dynamics may contribute to shaping defensive behavior.

Stress caused by external stressors, such as painful stimulation, can elicit a drastic set of behavioral responses. Such stress responses normally decay soon after the stressor disappears, but can become persistent when the stressor becomes longer and/or repeated. The neuronal mechanism underlying the persistence of stress responses, however, remains elusive. Here, we discovered that repeated electric shocks persistently suppress male Drosophila’s courtship behavior. We comprehensively evaluated the physiological changes in the genetically defined courtship circuitry, and found that a courtship-triggering node of the circuitry, called P1 neurons, is preferentially and persistently suppressed following electric shocks. Our data uncovers in a comprehensively defined courtship circuitry that repeated stress persistently suppresses a critical node of the circuitry in a targeted fashion to alter behavior.

Inactivation of the ubiquitin ligase Ube3a causes the developmental disorder Angelman syndrome, whereas increased Ube3a dosage is associated with autism spectrum disorders. Despite the enriched localization of Ube3a in the axon terminals including presynapses, little is known about the presynaptic function of Ube3a and mechanisms underlying its presynaptic localization. We show that developmental synapse elimination requires presynaptic Ube3a activity in Drosophila neurons. We further identified the domain of Ube3a that is required for its interaction with the kinesin motor. Angelman syndrome–associated missense mutations in the interaction domain attenuate presynaptic targeting of Ube3a and prevent synapse elimination. Conversely, increased Ube3a activity in presynapses leads to precocious synapse elimination and impairs synaptic transmission. Our findings reveal the physiological role of Ube3a and suggest potential pathogenic mechanisms associated with Ube3a dysregulation.

To remodel functional neuronal connectivity, neurons often alter dendrite arbors through elimination and subsequent regeneration of dendritic branches. However, the intrinsic mechanisms underlying this developmentally programmed dendrite regeneration and whether it shares common machinery with injury-induced regeneration remain largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons regenerate adult-specific dendrites after eliminating larval dendrites during metamorphosis. Here we show that the microRNA miR-87 is a critical regulator of dendrite regeneration in Drosophila. miR-87 knockout impairs dendrite regeneration after developmentally-programmed pruning, whereas miR-87 overexpression in C4da neurons leads to precocious initiation of dendrite regeneration. Genetic analyses indicate that the transcriptional repressor Tramtrack69 (Ttk69) is a functional target for miR-87-mediated repression as ttk69 expression is increased in miR-87 knockout neurons and reducing ttk69 expression restores dendrite regeneration to mutants lacking miR-87 function. We further show that miR-87 is required for dendrite regeneration after acute injury in the larval stage, providing a mechanistic link between developmentally programmed and injury-induced dendrite regeneration. These findings thus indicate that miR-87 promotes dendrite regrowth during regeneration at least in part through suppressing Ttk69 in Drosophila sensory neurons and suggest that developmental and injury-induced dendrite regeneration share a common intrinsic mechanism to reactivate dendrite growth. Dendrites are the primary sites for synaptic and sensory inputs. To remodel or repair neuronal connectivity, dendrites often exhibit large-scale structural changes that can be triggered by developmental signals, alterations in sensory inputs, or injury. Despite the importance of dendritic remodeling to nervous system function, the molecular basis for this remodeling is largely unknown. Here we used an unbiased genetic screen and in vivo imaging in Drosophila sensory neurons to demonstrate that the microRNA miR-87 is a critical factor required in neurons to reactivate dendritic growth both in developmental remodeling and following injury. Our work supports the model that miR-87 promotes dendrite regeneration by blocking expression of the transcriptional repressor Tramtrack69 in neurons. This study thus establishes a role for miRNAs in temporal control of dendrite regeneration.

Sexual dimorphisms are well recognized in various cardiac diseases such as ischemic cardiomyopathy (ICM), hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thorough understanding of the underlying genetic programs is crucial to optimize treatment strategies specified for each gender. By performing meta-analysis and microarray analysis, we sought to comprehensively characterize the sexual dimorphisms in the healthy and diseased heart at the level of both mRNA and miRNA transcriptome. Existing mRNA microarray data of both mouse and human heart were integrated, identifying dozens/ hundreds of sexually dimorphic genes in healthy heart, ICM, HCM, and DCM. These sexually dimorphic genes overrepresented gene ontologies (GOs) important for cardiac homeostasis. Further, microarray of miRNA, isolated from mouse sham left ventricle (LV) (n = 6 & n = 5 for male & female) and chronic MI LV (n = 19 & n = 19) and from human normal LV (n = 6 & n = 6) and ICM LV (n = 4 & n = 5), was conducted. This revealed that 13 mouse miRNAs are sexually dimorphic in MI and 6 in normal heart. In human, 3 miRNAs were sexually dimorphic in ICM and 15 in normal heart. These data revealed miRNA-mRNA networks that operate in a sexually-biased fashion. mRNA and miRNA transcriptome of normal and disease heart show significant sex differences, which might impact the cardiac homeostasis. Together this study provides the first comprehensive picture of the genome-wide program underlying the heart sexual dimorphisms, laying the foundation for gender specific treatment strategies.

We propose here a new idea to design filters which consist of low permittivity dielectric resonators placed in the two paths which are realized by a partial H-plane bifurcation in a rectangular waveguide. This type of filters is regarded as the parallel connection of two evanescent - mode waveguide filters. This paper will try to design such a filter with the Chebyshev's passband response and also with the stopband response with attenuation poles at desired frequencies, and practical performance aspects of this type of filters will be discussed from the view points of both analytical methods and experiments in the X-band.