Inducing Partner Preference in Mice by Chemogenetic Stimulation of CA2 Hippocampal Subfield

Social recognition is fundamental for social decision making and the establishment of long-lasting affiliative behaviors in behaviorally complex social groups. It is a critical step in establishing a selective preference for a social partner or group member. C57BL/6J lab mice do not form monogamous relationships, and typically do not show prolonged social preferences for familiar mice. The CA2 hippocampal subfield plays a crucial role in social memory and optogenetic stimulation of inputs to the dorsal CA2 field during a short memory acquisition period can enhance and extend social memories in mice. Here, we show that partner preference in mice can be induced by chemogenetic selective stimulation of the monosynaptic projections from the hypothalamic paraventricular nucleus (PVN) to the CA2 during the cohabitation period. Specifically, male mice spend more time in social contact, grooming and huddling with the partner compared to a novel female. Preference was not induced by prolonging the cohabitation period and allowing more time for social interactions and males to sire pups with the familiar female. These results suggest that PVN-to-CA2 projections are part of an evolutionarily conserved neural circuitry underlying the formation of social preference and may promote behavioral changes with appropriate stimulation

Optimization and validation of the NeuroLux wireless optoelectronics system for optogenetics

Utilizing light and genetic engineering, optogenetics permits the manipulation of events within cells via light using the light-sensitive properties of single-component microbial opsins. Microbial opsins are activated by a light source, such as lasers, light-emitting diodes, and incandescent sources that deliver light to the region of interest either directly or indirectly, such as through fiberoptics. In classical in vivo optogenetics, the wiring of optic fibers necessitates tethering of animals by the optic fiber to the light source. The novel NeuroLux wireless optoelectronic system for optogenetics circumvents issues pertaining to classical optogenetics by utilizing near-field power transfer via magnetic coil antennae to power miniature, subdermal, and flexible optoelectronic implants, including an LED light sources. Furthermore, features of the NeuroLux system overcome issues posed by other wireless systems, including interference. This preliminary study sought to validate and optimize the novel NeuroLux system setup by stimulating the cornu ammonis 2 (CA2) region of the hippocampus in transgenic mice that express Cre recombinase from the vasopressin 1b receptor promoter. Following experimentation, distinct stimulation, indicated by quantified cFos expression, was noted in the CA2 region, thereby validating the use of the NeuroLux wireless optoelectronics system for future optogenetics studies

NMDA Receptor in Vasopressin 1b Neurons Is Not Required for Short-Term Social Memory, Object Memory or Aggression

This work is licensed under a Creative Commons Attribution 4.0 International License.The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including aggression, social learning and memory. Genetic removal of Avpr1b from mouse models results in deficits in aggression and short-term social recognition in adults. Avpr1b gene expression is highly enriched in the pyramidal neurons of the hippocampal cornu ammonis 2 (CA2) region. Activity of the hippocampal CA2 has been shown to be required for normal short-term social recognition and aggressive behaviors. Vasopressin acts to enhance synaptic responses of CA2 neurons through a NMDA-receptor dependent mechanism. Genetic removal of the obligatory subunit of the NMDA receptor (Grin1) within distinct hippocampal regions impairs non-social learning and memory. However, the question of a direct role for NMDA receptor activity in Avpr1b neurons to modulate social behavior remains unclear. To answer this question, we first created a novel transgenic mouse line with Cre recombinase knocked into the Avpr1b coding region to genetically target Avpr1b neurons. We confirmed this line has dense Cre expression throughout the dorsal and ventral CA2 regions of the hippocampus, along with scattered expression within the caudate-putamen and olfactory bulb (OB). Conditional removal of the NMDA receptor was achieved by crossing our line to an available floxed Grin1 line. The resulting mice were measured on a battery of social and memory behavioral tests. Surprisingly, we did not observe any differences between Avpr1b-Grin1 knockout mice and their wildtype siblings. We conclude that mice without typical NMDA receptor function in Avpr1b neurons can develop normal aggression as well as short-term social and object memory performance

Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning

<div><p></p><p>Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.</p></div