Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.

Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion of Shank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

Ventromedial prefrontal neurons represent self-states shaped by vicarious fear in male mice.

Perception of fear induced by others in danger elicits complex vicarious fear responses and behavioral outputs. In rodents, observing a conspecific receive aversive stimuli leads to escape and freezing behavior. It remains unclear how these behavioral self-states in response to others in fear are neurophysiologically represented. Here, we assess such representations in the ventromedial prefrontal cortex (vmPFC), an essential site for empathy, in an observational fear (OF) paradigm in male mice. We classify the observer mouse's stereotypic behaviors during OF using a machine-learning approach. Optogenetic inhibition of the vmPFC specifically disrupts OF-induced escape behavior. In vivo Ca2+ imaging reveals that vmPFC neural populations represent intermingled information of other- and self-states. Distinct subpopulations are activated and suppressed by others' fear responses, simultaneously representing self-freezing states. This mixed selectivity requires inputs from the anterior cingulate cortex and the basolateral amygdala to regulate OF-induced escape behavior.

Disrupted social memory ensembles in the ventral hippocampus underlie social amnesia in autism-associated Shank3 mutant mice.

The ability to remember conspecifics is critical for adaptive cognitive functioning and social communication, and impairments of this ability are hallmarks of autism spectrum disorders (ASDs). Although hippocampal ventral CA1 (vCA1) neurons are known to store social memories, how their activities are coordinated remains unclear. Here we show that vCA1 social memory neurons, characterized by enhanced activity in response to memorized individuals, were preferentially reactivated during sharp-wave ripples (SPW-Rs). Spike sequences of these social replays reflected the temporal orders of neuronal activities within theta cycles during social experiences. In ASD model Shank3 knockout mice, the proportion of social memory neurons was reduced, and neuronal ensemble spike sequences during SPW-Rs were disrupted, which correlated with impaired discriminatory social behavior. These results suggest that SPW-R-mediated sequential reactivation of neuronal ensembles is a canonical mechanism for coordinating hippocampus-dependent social memories and its disruption underlie the pathophysiology of social memory defects associated with ASD.

Distinct functions of ventral CA1 and dorsal CA2 in social memory.

PURPOSE OF REVIEW: For animals that live in social groups, the ability to recognize conspecifics is essential. Recent studies of both human patients and animal models have vigorously sought to discern the precise mechanisms by which hippocampal neurons and neural circuits contribute to the encoding, consolidation, storage, and retrieval of social memory. In particular, optogenetic manipulation enables us to investigate the presence of memory engrams. RECENT FINDINGS: We recently revealed the presence of social memory engrams in hippocampal ventral CA1 neurons, using optogenetic manipulation and calcium (Ca2+) imaging. SUMMARY: In the present manuscript, we discuss the current viewpoints on two hippocampal subregions in regards to social memory representation, namely dorsal CA2 for information processing and ventral CA1 for the storage of social memory, specifically from the perspectives of behavioral neuroscience and neurophysiology.

Diverse sensory cues for individual recognition.

To be social, the ability to recognize and discriminate conspecific individuals is indispensable in social animals, including primates, rodents, birds, fish, and social insects which live in societies or groups. Recent studies using molecular biology, genetics, in vivo and in vitro physiology, and behavioral neuroscientific approaches have provided detailed insights into how animals process and recognize the information of individuals. Here, we review the most distinct sensory modalities for individual recognition in animals, namely, olfaction and vision. In the case of rodents, two polymorphic gene complexes have been identified in their urine as the key and essential pheromonal components for individual recognition: the major histocompatibility complex (MHC) and the major urinary protein (MUP). Animals flexibly utilize MHC and/or MUP, which are detected by the main olfactory epithelium (MOE) and/or the vomeronasal organ (VNO) for various types of social recognition, such as strain recognition, kin recognition, and individual recognition. In contrast, primates, including humans, primarily use facial appearance to identify others. Face recognition in humans and other animals is naturally unique from genetic, cognitive, developmental, and functional points of view. Importantly note that nurture effects during growth phase such as social experience and environment can also shape and tune this special cognitive ability, in order to distinguish subtle differences between individuals. In this review, we address such unique nature and nurture mechanisms for individual recognition.

Bumblebees Express Consistent, but Flexible, Speed-Accuracy Tactics Under Different Levels of Predation Threat.

A speed-accuracy trade-off (SAT) in behavioural decisions is known to occur in a wide range of vertebrate and invertebrate taxa. Accurate decisions often take longer for a given condition, while fast decisions can be inaccurate in some tasks. Speed-accuracy tactics are known to vary consistently among individuals, and show a degree of flexibility during colour discrimination tasks in bees. Such individual flexibility in speed-accuracy tactics is likely to be advantageous for animals exposed to fluctuating environments, such as changes in predation threat. We therefore test whether individual speed-accuracy tactics are fixed or flexible under different levels of predation threat in a model invertebrate, the bumblebee Bombus terrestris. The flexibility of speed-accuracy tactics in a foraging context was tested in the laboratory using a "meadow" of artificial flowers harbouring "robotic" crab spider predators. We found that while the ranking of bees along the speed and accuracy continuums was consistent across two levels of predation threat, there was some flexibility in the tactics used by individual bees - most bees became less accurate at colour discrimination when exposed to predation threat when flower types were rewarding. The relationship between decision speed and accuracy was influenced by predator detectability and the risk associated with making incorrect choices during the colour discrimination task. Predator crypsis resulted in a breakdown in the relationship between speed and accuracy, especially when making an incorrect floral choice incurred a distasteful quinine punishment. No single speed-accuracy tactic was found to be optimal in terms of foraging efficiency under either predation threat situation. However, bees that made faster decisions achieved higher nectar collection rates in predator free situations, while accurate bees achieved higher foraging rates under predation threat. Our findings show that while individual bees remain relatively consistent in terms of whether they place greater emphasis on speed or accuracy under predation threat, they can respond flexibly to the additional time costs of detecting predators.

Individual recognition and the 'face inversion effect' in medaka fish (Oryzias latipes).

Individual recognition (IR) is essential for maintaining various social interactions in a group, and face recognition is one of the most specialised cognitive abilities in IR. We used both a mating preference system and an electric shock conditioning experiment to test IR ability in medaka, and found that signals near the face are important. Medaka required more time to discriminate vertically inverted faces, but not horizontally shifted faces or inverted non-face objects. The ability may be comparable to the classic 'face inversion effect' in humans and some other mammals. Extra patterns added to the face also did not influence the IR. These findings suggest the possibility that the process of face recognition may differ from that used for other objects. The complex form of recognition may promote specific processing adaptations, although the mechanisms and neurological bases might differ in mammals and medaka. The ability to recognise other individuals is important for shaping animal societies.

[The design and implementation of video processing system for medical electronic endoscopy].

This paper presents a medical electronic endoscopy real-time image acquisition and control system which consists of video codec chip, flash memory and FPGA. The hardware scheme and circuit design of the system is figured out, and the principle of ping-pong operation and the implementation of FPGA program is introduced. Experimental tests show that the designed system performs steadily, is easy to maintain, and reduces the cost greatly. The higher performance price ratio makes it have good application prospect in medical endoscopy.