海马环路中的组合突触可塑性与大鼠情绪研究

海马在某些类型的学习和记忆中起着关键的作用，而突触可塑性（synaptic plasticity）为学习和记忆的模型提供了理论基础。在海马环路中，分布着各种类型的可塑性，包括突触特异的Hebbian形式的可塑性，如长时程增强（long-term potentiation，LTP）和长时程抑制（long-term depression，LTD）；稳态可塑性（homeostatic plasticity），如突触缩放（synaptic scaling）。稳态可塑性是一种整体的调控过程，它可以调节神经元甚至神经网络的平衡；而Hebbian可塑性则是突触特异的，即每个突触进行单独调控的过程。 越来越多的研究提示稳态可塑性和Hebbian可塑性之间存在着空间间隙（spatial gap），那么，如何使得神经元可以通过Hebbian可塑性的过程来维持细胞整体的兴奋性就变得尤为重要。一些报道揭示了LTP和LTD可以在同一突触通路中同时被激活，因此，我们提出组合突触可塑性的概念，即LTP和LTD的组合，它在赋予系统灵活性的同时又可以降低噪音维持系统的稳定性。基于此，本文将围绕这个问题而开展实验工作。 通过对海马CA1区锥体神经元的微小兴奋性突触后电流（miniature excitatory synaptic current, mEPSC）进行测定分析，我们发现mEPSC的幅度分布符合双峰正态分布（double-peak normal distribution）。Theta节律刺激（theta burst stimuli, TBS）诱导后，mEPSC的幅度分布发生改变，呈现右移趋势。随后，采用干扰肽Pep-A2特异地阻断LTP而不影响LTD，我们发现Pep-A2不影响基础状态下mEPSC的幅度分布。在干扰肽Pep-A2存在下，TBS诱导对基础状态下mEPSC的幅度分布也没有影响。结果为揭示LTP和LTD的组合可塑性提供了初步的证据，对进一步理解记忆的编码过程提供了一定的基础。社交隔离可以引起实验大鼠产生焦虑样和抑郁样的行为，而性经历可以改变动物的情绪状态，降低焦虑样和抑郁样的反应。然而，性经历后进行社交隔离对大鼠情绪的影响并没有报道。在这部分工作中，雄性大鼠经历一周的社交活动（male-male paired housing）或者性活动（male-female paired housing），随后进行一段时间的隔离（1天，2天或者7天）。我们发现，经历过性活动的大鼠，无论隔离与否都表现出相似的情绪反应，包括焦虑样和抑郁样行为以及超声波（ultrasonic vocalizations，USVs）发放；而未经历过性活动的大鼠，其情绪反应随着隔离时间的不同而不同。这一现象提示我们，先前的性经历可以对抗实验动物对环境应激事件，如社交隔离的反应。

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

Male mice song syntax depends on social contexts and influences female preferences.

In 2005, Holy and Guo advanced the idea that male mice produce ultrasonic vocalizations (USV) with some features similar to courtship songs of songbirds. Since then, studies showed that male mice emit USV songs in different contexts (sexual and other) and possess a multisyllabic repertoire. Debate still exists for and against plasticity in their vocalizations. But the use of a multisyllabic repertoire can increase potential flexibility and information, in how elements are organized and recombined, namely syntax. In many bird species, modulating song syntax has ethological relevance for sexual behavior and mate preferences. In this study we exposed adult male mice to different social contexts and developed a new approach of analyzing their USVs based on songbird syntax analysis. We found that male mice modify their syntax, including specific sequences, length of sequence, repertoire composition, and spectral features, according to stimulus and social context. Males emit longer and simpler syllables and sequences when singing to females, but more complex syllables and sequences in response to fresh female urine. Playback experiments show that the females prefer the complex songs over the simpler ones. We propose the complex songs are to lure females in, whereas the directed simpler sequences are used for direct courtship. These results suggest that although mice have a much more limited ability of song modification, they could still be used as animal models for understanding some vocal communication features that songbirds are used for.

An integrated multi-sensor data fusion algorithm and autopilot iImplementation in an uninhabited surface craft

Unmanned surface vehicles (USVs) are able to accomplish difficult and challenging tasks both in civilian and defence sectors without endangering human lives. Their ability to work round the clock makes them well-suited for matters that demand immediate attention. These issues include but not limited to mines countermeasures, measuring the extent of an oil spill and locating the source of a chemical discharge. A number of USV programmes have emerged in the last decade for a variety of aforementioned purposes. Springer USV is one such research project highlighted in this paper. The intention herein is to report results emanating from data acquired from experiments on the Springer vessel whilst testing its advanced navigation, guidance and control (NGC) subsystems. The algorithms developed for these systems are based on soft-computing methodologies. A novel form of data fusion navigation algorithm has been developed and integrated with a modified optimal controller. Experimental results are presented and analysed for various scenarios including single and multiple waypoints tracking and fixed and time-varying reference bearings. It is demonstrated that the proposed NGC system provides promising results despite the presence of modelling uncertainty and external disturbances.

A Review on Improving the Autonomy of Unmanned Surface Vehicles through Intelligent Collision Avoidance Manoeuvres

In recent years unmanned vehicles have grown in popularity, with an ever increasing number of applications in industry, the military and research within air, ground and marine domains. In particular, the challenges posed by unmanned marine vehicles in order to increase the level of autonomy include automatic obstacle avoidance and conformance with the Rules of the Road when navigating in the presence of other maritime traffic. The USV Master Plan which has been established for the US Navy outlines a list of objectives for improving autonomy in order to increase mission diversity and reduce the amount of supervisory intervention. This paper addresses the specific development needs based on notable research carried out to date, primarily with regard to navigation, guidance, control and motion planning. The integration of the International Regulations for Avoiding Collisions at Sea within the obstacle avoidance protocols seeks to prevent maritime accidents attributed to human error. The addition of these critical safety measures may be key to a future growth in demand for USVs, as they serve to pave the way for establishing legal policies for unmanned vessels.

Interactions between the cholinergic and dopaminergic systems during the production of ultrasonic vocalizations in rats

Rats produce ultrasonic vocalizations that can be categorized into two types of ultrasonic calls based on their sonographic structure. One group contains 22-kHz ultrasonic vocalization (USVs), characterized by relatively constant (flat) frequency with peak frequency ranging from 19 to 28-kHz, and a call duration ranging between 100 – 3000 ms. These vocalization can be induced by cholinomimetic agents injected into the ascending mesolimbic cholinergic system that terminates in the anterior hypothalamic-preoptic area (AH-MPO) and lateral septum (LS). The other group of USVs contains 50-kHz USVs, characterized by high peak frequency, ranging from 39 to 90-kHz, short duration ranging from 10-90 ms, and varying frequency and complex sonographic morphology. These vocalizations can be induced by dopaminergic agents injected into the nucleus accumbens, the target area for the mesolimbic dopaminergic system. 22-kHz USVs are emitted in situations that are highly aversive, such as proximity of a predator or anticipation of a foot shock, while 50 kHz USVs are emitted in rewarding and appetitive situations, such as juvenile play behaviour or anticipation of rewarding electrical brain stimulation. The activities of these two mesolimbic systems were postulated to be antagonistic to each other. The current thesis is focused on the interaction of these systems indexed by emission of relevant USVs. It was hypothesized that emission of 22 kHz USVs will be antagonized by prior activation of the dopaminergic system while emission of 50 kHz will be antagonized by prior activation of the cholinergic system. It was found that injection of apomorphine into the shell of the nucleus accumbens significantly decreased the number of carbachol-induced 22 kHz USVs from both AH-MPO and LS. Injection of carbachol into the LS significantly decreased the number of apomorphine-induced 50 kHz USVs from the shell of the nucleus accumbens. The results of the study supported the main hypotheses that the mesolimbic dopaminergic and cholinergic systems function in antagonism to each other.

Interactions between the cholinergic and dopaminergic system during the production of ultrasonic vocalizations in rats

Rats produce ultrasonic vocalizations that can be categorized into two types of ultrasonic calls based on their sonographic structure. One group contains 22-kHz ultrasonic vocalization (USVs), characterized by relatively constant (flat) frequency with peak frequency ranging from 19 to 28-kHz, and a call duration ranging between 100 – 3000 ms. These vocalization can be induced by cholinomimetic agents injected into the ascending mesolimbic cholinergic system that terminates in the anterior hypothalamic-preoptic area (AH-MPO) and lateral septum (LS). The other group of USVs contains 50-kHz USVs, characterized by high peak frequency, ranging from 39 to 90-kHz, short duration ranging from 10-90 ms, and varying frequency and complex sonographic morphology. These vocalizations can be induced by dopaminergic agents injected into the nucleus accumbens, the target area for the mesolimbic dopaminergic system. 22-kHz USVs are emitted in situations that are highly aversive, such as proximity of a predator or anticipation of a foot shock, while 50 kHz USVs are emitted in rewarding and appetitive situations, such as juvenile play behaviour or anticipation of rewarding electrical brain stimulation. The activities of these two mesolimbic systems were postulated to be antagonistic to each other. The current thesis is focused on the interaction of these systems indexed by emission of relevant USVs. It was hypothesized that emission of 22 kHz USVs will be antagonized by prior activation of the dopaminergic system while emission of 50 kHz will be antagonized by prior activation of the cholinergic system. It was found that injection of apomorphine into the shell of the nucleus accumbens significantly decreased the number of carbachol-induced 22 kHz USVs from both AH-MPO and LS. Injection of carbachol into the LS significantly decreased the number of apomorphine-induced 50 kHz USVs from the shell of the nucleus accumbens. The results of the study supported the main hypotheses that the mesolimbic dopaminergic and cholinergic systems function in antagonism to each other.