156 research outputs found
Fluoxetine treatment rewires vestibular circuitry and corrects deficits in egocentric navigation of adult mice
No full textAs egocentric navigation relies on vestibular input, neonatal exposure of the medial vestibular nucleus (MVN) to GABAA receptor antagonist bicuculline (BIC) produced navigation impairment in adult mice. Fluoxetine (FLX), a selective serotonin (5-HT) reuptake inhibitor, is known to reinstate exclusive plasticity in mature neural circuitry. Co-treatment of FLX and wobble vestibular stimulation (WOB) in these mice at postnatal day (P) 21-28 was shown to correct such navigation deficits in adulthood. This study hypothesizes that FLX+WOB treatment resets the deranged vestibular circuitry for egocentric navigation.
Since the transplantation of immature neuron can reinstate plasticity in mature circuitry, it was examined whether FLX treatment induces neurogenesis in the MVN, thereby abolishing navigation deficits. Prominin1 (PROM1)-expressing stem cells in the (sub-)ependymal layer of the fourth ventricle were hypothesized to provide the neighboring MVN neuron progenitors which proliferate with FLX induction. Both in vivo genetic lineage tracing and in vitro neurosphere assay found no neurons differentiated from PROM1 progeny in the MVN and (sub-)ependymal layer. FLX, or 5-HT mimicking its effect in vitro, did not promote proliferation of cells in the MVN. These results illustrate that the mechanism underlying FLX+WOB treatment might be independent of cell proliferation.
To ascertain whether FLX+WOB treatment alters the connectivity of GABAergic parvalbumin (PV)-expressing MVN neurons, thereby abolishing navigation deficits, various virus tracing tools were used to elucidate the central vestibular circuitry. Through anterograde monosynaptic tracing, postsynaptic targets of these PV neurons were found in relays of the circuitry for egocentric navigation, including the nucleus prepositus hypoglossi (NPH), dorsal paragigantocellular reticular nucleus (PGRNd), supragenual nucleus (SGN), and dorsal tegmental nucleus (DTN). In this ascending vestibular circuitry, SGN processes direct input from the MVN for generating head direction signals. Projection to the SGN from the MVN was mainly ipsilateral, with over 30% of SGN-projecting MVN neurons expressing PV. Retrograde monosynaptic tracing further demonstrated that neonatal BIC exposure and subsequent FLX+WOB treatment had no effect on input from the aforementioned relays onto SGN-projecting MVN neurons.
Viral retrograde tracing revealed that neonatal BIC exposure increased the projection of PV-expressing MVN neurons to the contralateral SGN but reduced such projection to the bilateral DTN. The deranged projection of PV neurons in this ascending circuitry may be responsible for the BIC-induced deficits in egocentric navigation.
Compared with mice with BIC treatment only, anterograde monosynaptic tracing revealed that BIC and subsequent FLX+WOB treatments reduced the number of ipsilateral NPH neurons postsynaptic to PV-expressing MVN neurons. This provided evidence that FLX+WOB treatment rewired the ascending vestibular circuitry, thereby contributing to the correction of BIC-induced deficits in egocentric navigation.
To conclude, neonatal BIC produced derangement in vestibular circuitry and caused deficits in egocentric navigation of adult mice. FLX+WOB treatment induced re-establishment of the circuitry and corrected the navigation deficits. These results shed light on how miswiring of vestibular circuitry for navigation may occur and offer a therapeutic approach for restoring egocentric navigation in adults through harnessing the plasticity of vestibular circuitry.published_or_final_versionBiomedical SciencesDoctoralDoctor of Philosoph
Effects of environmental enrichment on cortical synaptic plasticity in mouse models of schizophrenia : involvement of parvalbumin interneurons
No full textN-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin-expressing interneuron (PV interneuron) deficit are both implicated in the pathogenesis of schizophrenia. Pharmacological NMDAR antagonism has been widely used as an animal model for studying the pathogenesis of schizophrenia. However, the effects of NMDAR antagonism on the structural plasticity of excitatory and inhibitory synapses during development remain unexplored.
Using in vivo two-photon microscopy, the dynamic plasticity of the dendritic spine of pyramidal neurons and en passant axonal bouton of PV interneurons (PV axonal bouton) in mouse frontal association cortex (FrA) was examined in an NMDAR antagonism model. It was found that repeated exposure to the NMDAR antagonist dizocilpine maleate (MK801) during adolescence induced schizophrenic-related behaviors and significant reduction of dendritic spine formation of layer 5 pyramidal neurons in a dose-dependent manner. Simultaneous longitudinal imaging of dendritic spine of layer 5 pyramidal neurons and en passant axonal bouton of layer 2/3 PV interneurons showed that MK801 disrupted the normal developmental balance of excitatory and inhibitory (E/I) synaptic structures by enhancing the elimination of PV axonal boutons and reducing the formation of dendritic spines and PV axonal boutons. This MK801-induced structural E/I imbalance was ameliorated by environmental enrichment (EE), and the structural E/I value significantly correlated with animal working memory in novel object recognition. Besides, selective chemogenetic activation of PV interneurons in the FrA mimicked the effects of EE on both the dendritic spine and PV axonal bouton dynamics and animal behaviors, while selective inhibition of PV interneurons abolished the beneficial effects of EE.
In addition, the dynamic plasticity of the dendritic spine of layer 2/3 pyramidal neurons was also studied in the NMDAR antagonism model. It was found that repeated exposure to MK801 during adolescence caused not only a reduction in the rate of spine formation but also an enhancement in the rate of spine elimination. Furthermore, EE exerted a delayed beneficial effect on dendritic spine plasticity of layer 2/3 pyramidal neurons when compared to layer 5, while selective activation of PV interneurons in the FrA showed no such delay in repeated exposure of MK801. On the other hand, selective inhibition of PV interneurons abolished the beneficial effects of EE on layer 2/3 dendritic spine plasticity.
Next, I asked whether the involvement of PV interneurons in the beneficial action of EE on synapses and behavior can also apply to the genetic model of schizophrenia. Here a PV-Cre; ErbB4fl/fl conditional knockout (cKO) mouse, where ErbB4 was selectively ablated in PV interneurons, was used. It was found that the cKO mice displayed schizophrenia-like behaviors and both dendritic spine and PV axonal bouton deficits during adolescence, while these behavioral and synaptic deficits were rescued by activating frontal PV interneurons.
Collectively, these findings suggest that the PV interneuron activity in the FrA is crucial for excitatory and inhibitory synaptic structural dynamics and animal behavior in NMDAR hypofunction and PV interneuron deficits schizophrenia animal models, which demonstrate the crucial roles of PV interneuron activity and provide a potential therapeutic target for the treatment of schizophrenia.published_or_final_versionBiomedical SciencesDoctoralDoctor of Philosoph
Distinct vestibular neuron subtypes contribute to navigation and motor coordination
No full textThe vestibular system, referred to as the sixth sense, plays a vital role in spatial navigation and motor coordination, with the central vestibular nucleus as the first processing center. However, there is still much that remains unknown regarding the specific contributions from neuronal subtypes in the medial vestibular nucleus (MVN), particularly the parvalbumin-expressing (PV) and somatostatin-expressing (SST) neurons.
First, this study identified in mice an uncharted long-range projection of excitatory PVMVN neurons that directly innervate the midbrain dorsal tegmental nucleus (DTN) monosynaptically. It is further proved that this PVMVN→DTN projection is imperative for efficient navigational function. Moreover, both decreased number and diminished drive of PVMVN→DTN synapses were pinpointed as hallmarks of age-related navigational deficits. Notably, chemogenetic activation of this pathway ameliorated navigational decline in aged mice, as evidenced by increased accuracy in heading direction and effective switching of navigational strategies. In sum, these results demonstrated for the first time how a newly identified excitatory PV pathway from the brainstem participates in navigational circuits and changes along aging, suggesting a viable cellular candidate for targeted therapies that mitigate navigational impairments.
Second, this study also found that SST neurons within the MVN are essential for motor coordination. SST neurons contribute to the integration of sensory signals and modulation of downstream motor pathways, ensuring smooth and coordinated movements.
In summary, the segregated roles of PV and SST neurons in the MVN contribute to navigation and motor coordination, respectively. The PVMVN→DTN pathway is crucial for efficient navigation, and its dysregulation during aging underscores its potential as a cellular target for therapeutic interventions. Investigations into the roles of SST neurons further enhance our understanding of motor coordination mechanisms. These findings open exciting avenues for developing targeted therapies to address navigation and motor coordination impairments in various neurological conditions.published_or_final_versionBiomedical SciencesDoctoralDoctor of Philosoph
Impact of neuromodulators on the maturation and rewiring of neural circuitry for vestibular-dependent behaviors
No full textExperience-dependent plasticity during early postnatal development of the nervous system enables hardwiring of neural circuits to sensory experiences. Disruptions in neurodevelopment within this time window result in deficits that persist into adulthood. γ-aminobutyric acid (GABA) and endocannabinoid (eCB) are crucial for the control of postnatal synaptic plasticity. Findings from our laboratory revealed that neonatal blockade of GABAergic transmission in the brainstem vestibular nucleus (VN) of rats led to an over-activation of neurons in the anterodorsal thalamic nucleus (ADN), a key station in the ascending vestibular pathway for spatial cognition. This was accompanied by deficits in spatial navigation observed in adulthood. Similar behavioural deficits were also observed with over-activation of eCB receptors in VN at the neonatal stage.
In this study, we aimed at rescuing behavioural deficits by reinstating experience-dependent plasticity in adult rats that had received neonatal perturbation of either GABA or eCB receptors in the VN. Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is well known to re-activate neuroplasticity in several sensory systems of adult animals. We hypothesized that concurrent treatment of FLX with counter-clockwise wobble rotation (WOB) in adult rats can reinstate the plasticity of early-deranged vestibular circuitries and provide the necessary vestibular-specific sensory input to reshape the vestibular circuitry for executing normal spatial navigation.
To demonstrate experience-dependent rewiring in the vestibular circuit during this period of plasticity, we examined the level of activation among vestibular-related neurons in the ADN. Combined treatment of FLX+WOB in rats with neonatal vestibular derangement restored vestibular-related activity in the ADN, as indicated by the number of functionally activated Fos-immunoreactive neurons. In addition, rats that suffered from neonatal vestibular derangement showed a recovery in spatial navigation ability. Nevertheless, sole treatment of FLX or WOB alone did not result in such recovery at both the cellular and behavioural level.
Given that enhanced VN activity to the thalamus led to derangement of spatial navigation, we probed the possible role of inhibitory VN neurons in spatial navigation. With the use of chemogenetic tools, we modulated the activity of two major types of inhibitory interneurons in the VN, i.e. parvalbumin (PV+) and somatostatin (SST+) interneurons. We found that these interneurons did not play a significant role in spatial navigation, though there were indications that these interneurons were indeed involved in vestibulospinal reflexes for maintenance of posture and balance.
Altogether, we demonstrate the possibility of engaging neuromodulators in reshaping deranged neural circuitries in the adult VN by experience-dependent rewiring during a period of FLX-induced plasticity. This forms the basis for the design and refinement of therapeutic strategies for neurorehabilitation. In addition, the results provide insights towards the role of inhibitory interneurons in the central vestibular system.published_or_final_versionBiomedical SciencesMasterMaster of Philosoph
Coding with side information
No full textSource coding and channel coding are two important problems in communications. Although side information exists in everyday scenario, the effect of side information is not taken into account in the conventional setups. In this thesis, we focus on the practical designs of two interesting coding problems with side information: Wyner-Ziv coding (source coding with side information at the decoder) and Gel??fand-Pinsker coding (channel coding with side information at the encoder).
For WZC, we split the design problem into the two cases when the distortion of the reconstructed source is zero and when it is not. We review that the first case, which is commonly called Slepian-Wolf coding (SWC), can be implemented using conventional channel coding. Then, we detail the SWC design using the low-density parity-check (LDPC) code. To facilitate SWC design, we justify a necessary requirement that the SWC performance should be independent of the input source. We show that a sufficient condition of this requirement is that the hypothetical channel between the source and the side information satisfies a symmetry condition dubbed dual symmetry. Furthermore, under that dual symmetry condition, SWC design problem can be simply treated as LDPC coding design over the hypothetical channel.
When the distortion of the reconstructed source is non-zero, we propose a practical WZC paradigm called Slepian-Wolf coded quantization (SWCQ) by combining SWC and nested lattice quantization. We point out an interesting analogy between SWCQ and entropy coded quantization in classic source coding. Furthermore, a practical scheme of SWCQ using 1-D nested lattice quantization and LDPC is implemented.
For GPC, since the actual design procedure relies on the more precise setting of the problem, we choose to investigate the design of GPC as the form of a digital watermarking problem as digital watermarking is the precise dual of WZC. We then introduce an enhanced version of the well-known spread spectrum watermarking technique. Two applications related to digital watermarking are presented
Long-term observation of the Soya Warm Current using HF ocean radars: relationship between the Soya Warm Current variability and the sea level anomalies in the Soya/La Perouse Strait
No full textThree high-frequency (HF) ocean radars were installed at the Soya/La Perouse Strait to monitor the surface current fields of the Soya Warm Current (SWC), which flows through the strait from the Sea of Japan to the Sea of Okhotsk. These ocean radars were operated for 19 years, from August 2003 to March 2022. In this paper, seasonal to interannual variations in the SWC were investigated using surface current fields obtained by the HF ocean radars combined with coastal tide gauge records and sea level anomaly from satellite altimetry. The HF ocean radars clearly captured the seasonal and interannual variations in the SWC. The alongshore surface velocity of SWC showed a high correlation with the alongshore sea level difference (SLD) between the Sea of Japan and the Sea of Okhotsk if seasonal variations were included. However, anomalies of the SLD and SWC alongshore velocity exhibited a lower correlation, especially in summer. This suggests that different mechanisms may be involved in summer and winter. The alongshore SLD between Wakkanai and Abashiri, which has been utilized in previous studies as an indicator of SWC intensity, may not be appropriate for representing interannual variations in the SWC intensity in summer, when the SWC reaches the maximum current velocity. Instead, it was demonstrated that the offshore SLD anomaly estimated using satellite altimetry with the coastal tide gauge record at Wakkanai could be a better index for representing the interannual variations throughout the year
The indirect approach
No full textAid and conditionalities are the"carrots and sticks"of the conventional, direct approach to fostering economic development. The economic theory of agency is the most sophisticated treatment of the direct carrots-and-sticks approach to influencing human behavior. Considering the outcomes of the conventional approach, it might be worthwhile to explore alternative indirect approaches that focus on enabling clients to act more autonomously, rather than try for fuller control of clients'actions (or"agents"behaviors) with improved carrots and sticks. Are there inherent limitations in the direct approach that will not be addressed with better crafted"agency contracts"or closer monitoring of the agents? The author traces the intellectual history of indirect approaches from Socrates to modern thinkers, such as Wittgenstein, Gandhi, and McGregor. One theme of his survey is that constructivist and active-learning pedagogies constitute an indirect approach in which the teacher does not directly transmit knowledge to the learner, through training, and instruction. These pedagogies - translated into social and economic development as learning writ large - from the basis for an alternative indirect approach to fostering development. Actions have motives, just as beliefs have grounds, concludes the author. In the wide spectrum of human endeavor, there is only a fairly small"bandwidth"in which motives can be supplied by the carrots, and sticks of the direct approach (including agency theory, and market-driven activities as special cases of the direct approach to affecting behavior). Outside that spectrum, trying to use direct methods in a controlling manner, contradicts the motives for actions (and the grounds for beliefs) - like trying to"buy love."For higher activities, motives must come from within. Helpers can at best use an indirect approach to bring doers to the threshold; the doers have to do the rest, which makes the results their own.Public Health Promotion,Teaching and Learning,Curriculum&Instruction,Health Monitoring&Evaluation,Educational Sciences,Educational Sciences,Teaching and Learning,Health Monitoring&Evaluation,General Technology,Curriculum&Instruction
Further validation of the Chinese version of the Level of Expressed Emotion Scale for research and clinical use
No full text2009-2010 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishedGreen (AAM
Bolstering Measures for Combating the Challenges of Safe Working Cycle Implementation in Hong Kong’s Construction Industry
No full textTo heighten the safety performance of construction projects, multitudinous safety initiatives or measures have been promulgated in Hong Kong over the past three decades. These initiatives have led to the drastic reduction in construction site accidents. However, implementing these safety initiatives, such as the Safe Working Cycle (SWC), does not go without facing challenges. This paper illustrates the survey findings from an evaluation of the challenges encountered with the execution of SWC in construction projects in Hong Kong and proffers possible bolstering improvement measures for its successful implementation. The study was quantitative in nature and data were gathered from construction participants involved in projects adopting SWC. The data gathered were analysed using diverse descriptive, inferential and first-generation multivariate analyses. The study findings revealed that the effective implementation of SWC is still deterred by several major challenges that can be grouped into: (1) tight project schedule and limited site space; and (2) lack of promotions and support for SWC implementation. To address these profound challenges, the study recommended some essential improvement measures including: (1) adequate budget allocation and reasonable project schedule; (2) establishment of a reward system towards construction workers; and (3) development of a tailor-made SWC system for each specific construction site. The study has provided useful guidelines and insightful recommendations for both the client organisations and construction firms and their site management staff in developing their site safety policies and adopting SWC for improving the existing site safety performance of various construction projects
A method for predicting the occurrence of paralytic shellfish poisoning along the coast of Hokkaido in the Okhotsk Sea in summer
No full textTo design a method for predicting outbreaks of paralytic shellfish poisoning (PSP) in scallop fishing grounds, the relationship between the distribution of the toxic dinoflagellate Alexandrium tamarense and the dynamics of the Soya Warm Current (SWC) was examined in the Okhotsk Sea off Hokkaido. Surveys were conducted from May to June to clarify the transportation mechanism of A. tamarense from the oceanic area to the coastal area. The sea-level difference (SLD) between Wakkanai and Abashiri was monitored as an index of the strength of the SWC southeastward flow in an alongshore belt to examine the possible occurrence of A. tamarense in the coastal area during temporal weakening of the SWC. A bottom-mounted ADCP was used for direct observations of the SWC. The results indicated that PSP occurred when low salinity water contaminated with A. tamarense extended to the coast during the temporal weakening of the SWC due to a decrease of the SLD. Our results strongly indicate that predictions can be realized by monitoring the decrease of SLD as an index of temporal weakening of the SWC after surveys of the distribution of A. tamarense in the oceanic area before the period of PSP occurrence
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