57 research outputs found
Deciphering the behavioral dynamics and neural circuit mechanisms for conflicting memories in D. melanogaster olfactory learning
No full textAnimals constantly face choices between competing outcomes – whether to approach a reward or avoid a threat. Understanding how the brain integrates conflicting information to make such decisions is a fundamental question in neuroscience. Drosophila melanogaster is the ideal model for this question based on the recently published connectome and robust genetic tools that allows for specific neuron targeting. The mushroom body in Drosophila integrates sensory stimuli with reinforcement signals to assign valence to odors, but how flies resolve conflicting memories remains unclear. To address the neural basis of choice behavior, we are establishing a novel behavioral framework using a fly-on-a-ball treadmill paradigm that enables precise pairing of sensory stimuli with both appetitive and aversive cues. This setup lays the foundation for future physiological studies by allowing brain activities in tethered, behaving flies to be imaged during memory-guided decision-making. The first portion of the project includes optogenetic activation of reward-signaling dopaminergic neurons and sugar sensory neurons. Behavioral assays revealed a significant increase in the speed of locomotion evoked by an odor paired with activation of the dopaminergic neurons, while a control unpaired odor evoked no significant change. On the other hand, we could not observe an obvious effect of pairing with sugar sensory neurons. The second portion of the project was dedicated to optimizing a method to deliver electric shocks to tethered flies without impeding locomotion, enabling future studies on aversive learning and conflict resolution. By developing a precise and repeatable paradigm for creating and testing conflicting memories, this project establishes the groundwork for future imaging-based experiments on how flies make decisions when faced with competing internal drives.Bachelor of Scienc
Learning: The Good, the Bad, and the Fly
No full textOlfactory memories can be very good—your mother’s baking—or very bad—your father’s cooking. We go through life forming these different associations with the smells we encounter. But what makes one association pleasant and another repulsive? Work in deep areas of the Drosophila brain has revealed the beginnings of an answer, as reported in this issue of Neuron by Owald et al. (2015)
シンケイ ステロイド ニ ヨル シナプス ゾウキョウ キコウ ノ ケンキュウ
No full text京都大学0048新制・課程博士博士(理学)甲第13653号理博第3311号新制||理||1487(附属図書館)UT51-2008-C571京都大学大学院理学研究科生物科学専攻(主査)教授 藤吉 好則, 教授 平野 丈夫, 教授 阿形 清和学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDA
Neural circuits underlying sensory integration in secondary auditory cortex
No full textOur sensory systems are constantly inundated with information from the external world, which is converted into neural representations that guide our behavior. Much of this processing occurs in the cerebral cortex, which consists of numerous functionally-specialized areas that form hierarchically organized streams to support diverse sensory computations. Dissecting the discrete roles of these brain regions is therefore crucial for our understanding of the neural circuits of sensory processing in neurotypical brains, as well as how they are altered to cause atypical responses to sensory information in neurodevelopmental disorders. Determining the roles of discrete areas requires functional parcellation of brain structures and their precise targeting for manipulation. In Chapter 2, we evaluated the accuracy of brain area delineation in standardized brain atlases by mapping functionally-identified auditory cortical areas onto bregma-based stereotaxic coordinates. We found that auditory areas in the brain atlas correlate poorly with the true complexity of functional area boundaries, indicating the necessity of functional mapping in individual animals to dissect cortical area-specific roles with high precision. We took advantage of the precision of functional mapping in Chapter 3, to dissect the role of secondary auditory cortex (A2) in the integration of multi-frequency harmonic sounds, which is critical for recognizing syllables in speech. The “feature binding” of harmonic components relies on the precise synchrony of each component’s onset timing, but little is known regarding its neural correlates. We found that coincident harmonic sounds preferentially activate A2, whose response deteriorates with shifts in component onset timings. We propose A2 as a locus for multi-frequency integration, which may form the circuit basis for vocal processing. Finally, in Chapter 4, we aimed to understand how changes in global connectivity between hierarchically-organized brain areas contribute to altered sensory processing in neurodevelopmental disorders. Using a mouse model for Angelman syndrome, we investigate the circuit-level consequences of top-down modulatory inputs from A2 while performing electrophysiological recordings in primary auditory cortex (A1) as mice engage in a task for sustained attention. Overall, this work will expand our knowledge of how functionally-discrete brain regions encode sensory information in both neurotypical and neurodivergent brains.Doctor of Philosoph
Roles of feedback and feed-forward networks of dopamine subsystems: insights from Drosophila studies
No full textAcross animal species, dopamine-operated memory systems comprise anatomically segregated, functionally diverse subsystems. Although individual subsystems could operate independently to support distinct types of memory, the logical interplay between subsystems is expected to enable more complex memory processing by allowing existing memory to influence future learning. Recent comprehensive ultrastructural analysis of the Drosophila mushroom body revealed intricate networks interconnecting the dopamine subsystems-the mushroom body compartments. Here, we review the functions of some of these connections that are beginning to be understood. Memory consolidation is mediated by two different forms of network: A recurrent feedback loop within a compartment maintains sustained dopamine activity required for consolidation, whereas feed-forward connections across compartments allow short-term memory formation in one compartment to open the gate for long-term memory formation in another compartment. Extinction and reversal of aversive memory rely on a similar feed-forward circuit motif that signals omission of punishment as a reward, which triggers plasticity that counteracts the original aversive memory trace. Finally, indirect feed-forward connections from a long-term memory compartment to short-term memory compartments mediate higher-order conditioning. Collectively, these emerging studies indicate that feedback control and hierarchical connectivity allow the dopamine subsystems to work cooperatively to support diverse and complex forms of learning
Cyclic nucleotide‐induced bidirectional long‐term synaptic plasticity in Drosophila mushroom body
No full textActivation of the cAMP pathway is one of the common mechanisms underlying long-term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour-coding Kenyon cells (KCs) and reinforcement-coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long-term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short-term and long-term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP-protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin-induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second-messenger pathways predicted by behavioural study. Finally, KC subtype-specific interrogation of synapses revealed that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. KEY POINTS: Although presynaptic cAMP increase generally facilitates synapses, olfactory associative learning in Drosophila, which depends on dopamine and cAMP signalling genes, induces long-term depression (LTD) at the mushroom body output synapses. By combining electrophysiology, pharmacology and optogenetics, we directly demonstrate that these synapses are an exception where activation of the cAMP-protein kinase A pathway leads to presynaptic LTD. Dopamine- or forskolin-induced cAMP increase alone is not sufficient for LTD induction; neuronal activity, which has been believed to trigger cAMP synthesis in synergy with dopamine input, is required in the downstream pathway of cAMP. In contrast to cAMP, activation of the cGMP pathway paired with neuronal activity induces presynaptic long-term potentiation, which explains behaviourally observed opposing actions of transmitters co-released by dopaminergic neurons. Our work not only revises the role of cAMP in synaptic plasticity, but also provides essential methods to address physiological mechanisms of synaptic plasticity in this important model system
Influence of amino acid residues near the active site of cytochrome P450 from Bacillus megaterium on the selectivity of n-octane oxidation to octanol regioisomers
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<Articles>A Study on Bandobon (坂東本) of Kyogyoshinsho (教行信證) (Studies on the History of Ideas)
No full text教行信証についての最近の研究は、信巻別撰説をめぐる構成の面と、元仁元年を中心とする著述年次の面に、関心を集中しているが、双方とも論は坂東本に関係しており、その実態についての研究が要望されている。この論文は、著者がこの二年間、坂東本について直接調査した結果を纒めたものであり、書誌学的研究に属するが、それから導き出される結論は、教行信証の構成や著述年次についての論議に関係するので、思想史特集のうちに含めて発表することにした。論文の重点を要約して云えば、坂東本のうちには、当初に書写されたままの個所と、後に書直された部分があり、いままでの研究ではこれを区別せずに同じに取扱ってきたが、原本についてその区別を明らかにし、それによって教行信証の研究に新しい面を開こうとするものである。Resent studies of Kyogyoshinsho by Shinran (親鸞) have been centered on how the volume of Shinkan (信卷) was inserted later and, chronologically, how the prodedure of description was taken, though certainly it occurred around the first year of Gannin(元仁). Discussions in both ways are based on Bandobon, i. e. the original copy. This article results from the author's two-year-long direct investigation of that copy. The article, though primarily bibliographical, is believed to take part in the above discussions. In short, the Bandobon contains two parts, original and additional. So far historians have not distinguish these parts when they treat them as historical sources. Here the author has made clear the differences and intends to open a new way for the study of Kyogysohinsho
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