Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Medial Preoptic Area Modulates Courtship Ultrasonic Vocalization in Adult Male Mice / 神经科学通报·英文版

Adult male mice emit highly complex ultrasonic vocalizations (USVs) in response to female conspecifics. Such USVs, thought to facilitate courtship behaviors, are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism. While the regulation of USVs by genetic factors has been extensively characterized, the neural mechanisms that control USV production remain largely unknown. Here, we report that optogenetic activation of the medial preoptic area (mPOA) elicited the production of USVs that were acoustically similar to courtship USVs in adult mice. Moreover, mPOA vesicular GABA transporter-positive (Vgat +) neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons. Furthermore, ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males. Together, these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.

Effects of the Female Estrous Cycle on the Sexual Behaviors and Ultrasonic Vocalizations of Male C57BL/6 and Autistic BTBR T+ tf/J Mice

A primary characteristic of autism, which is a neurodevelopmental disorder, is impaired social interaction and communication. Furthermore, patients with autism frequently show abnormal social recognition. In mouse models of autism, social recognition is usually assessed by examining same-sex social behavior using various tests, such as the three-chamber test. However, no studies have examined the ability of male mice with autism to recognize the estrous cycle of female partners. In this study, we investigated the sexual behaviors, especially mounting and ultrasonic vocal communication (USV), of BTBR T+ tf/J (BTBR) mice, which are used as a well-known mouse model of autism, when they encountered estrus or diestrus female mice. As expected, C57BL/6 mice mounted more female mice in the estrus stage compared with the diestrus stage. We found that BTBR mice also mounted more female mice in the estrus stage than female mice in the diestrus stage. Although the USV emission of male mice was not different between estrus and diestrus female mice in both strains, the mounting result implies that BTBR mice distinguish sexual receptivity of females.

Strain- and context-based 50 kHz ultrasonic vocalizations and anxiety behaviour in the Wistar-Kyoto rat.

Rodent ultrasonic vocalizations (USVs) are influenced by immediate, prior contexts and have emerged as important indicators that monitor an individual’s ‘state’. They also index direct reflections of inherent ‘trait’ and are suggested to constitute non-invasive read-outs of pathological conditions. Analysis of USVs emitted under particular contexts could help discern strain-specific differences and existence of individual USV profiles. USVs of the Wistar-Kyoto (WKY) strain, a putative model of depression, could indicate social communication deficits. In the cage, USV emission was significantly reduced in WKYs. An elevated plus maze exposure led to no change in USV emission in WKYs, while it significantly reduced USVs in Wistars. Re-exposure induced strain-specific differences in behaviour and total calling time. Sonographic patterns indicated that the predominant USV subtype were flat 50 kHz USVs. EPMexposure induced a reduction in peak amplitude in WKY USVs and in USV length in both strains. USV peak frequency and amplitude, genetically determined spectral features, were strain-specific, while bandwidth and temporal features such as total calling time and USV duration were context-dependent. WKY USVs demonstrated characteristic spectral structures such as increased call length and reduced peak frequency while other parameters were not quantitatively different, reflecting the shared phylogeny between Wistars and WKYs.

Quantitative and qualitative analysis of rat pup ultrasonic vocalization sounds induced by a hypothermic stimulus / 한국실험동물학회지

Ultrasonic vocalizations (USVs) are essential communicative sounds used between rodent pups and their mother. Rat pups emit USVs in stressful situations, such as when they are cold or separated from the nest. We verified the ontogenetic changes in USVs emitted by infant rats isolated from their mother during the pre-weaning period. The number of calls, and the median frequency and first peak of frequency of the calls were measured at 1, 3, 5, 7, 10, 12, and 14 days postnatal age in Wistar-Imamichi rats. Pups were placed in a cold glass beaker and USVs were recorded for 5 min. The number of calls increased to a peak on day 5 and then gradually decreased. The median frequency of calls decreased slowly during the first 12 days, and then increased slightly on day 14. Similarly, the first peak frequency of calls was the highest on day 1, and then decreased gradually by day 12. A small increase was observed on day 14. These changes in frequency were correlated with the physical development of the pups, whose body weights increased significantly with age except during postnatal days 7-10.

Ultrasound call detection in capybara / Detecção de chamados de ultrassom em capivara

The vocal repertoire of some animal species has been considered a non-invasive tool to predict distress reactivity. In rats ultrasound emissions were reported as distress indicator. Capybaras[ vocal repertoire was reported recently and seems to have ultrasound calls, but this has not yet been confirmed. Thus, in order to check if a poor state of welfare was linked to ultrasound calls in the capybara vocal repertoire, the aim of this study was to track the presence of ultrasound emissions in 11 animals under three conditions: 1) unrestrained; 2) intermediately restrained, and 3) highly restrained. The ultrasound track identified frequencies in the range of 31.8±3.5 kHz in adults and 33.2±8.5 kHz in juveniles. These ultrasound frequencies occurred only when animals were highly restrained, physically restrained or injured during handling. We concluded that these calls with ultrasound components are related to pain and restraint because they did not occur when animals were free of restraint. Thus we suggest that this vocalization may be used as an additional tool to assess capybaras[ welfare.

O repertório vocal de algumas espécies de animais tem sido considerado uma ferramenta não invasiva para predizer o distresse. Em ratos, emissões de ultrassom foram registradas como indicador de distresse. O repertório vocal de capivaras foi relatado recentemente e parece haver a presença de chamados em ultrassom que ainda não foram confirmados. Assim para associar o estado de bem-estar empobrecido em capivaras e a possibilidade de ocorrência de ultrassom em seu repertório vocal, o presente estudo teve como objetivo rastrear a presença deste tipo de vocalização em 11 animais submetidos a três condições diferentes: 1) sem contenção; 2) média contenção e 3) alta contenção. O rastreamento revelou a presença de faixas de frequência de 31,8±3,5 kHz em adultos e 33,2±8,5 kHz em filhotes. Estas emissões encontradas na faixa de ultrassom ocorreram apenas durante a alta contenção, quando contidos fisicamente ou feridos durante o manejo. Concluímos que tais emissões, com componentes de ultrassom, estão relacionadas à dor e ao distresse de contenção pois não ocorreram quando os animais estavam livres de contenção. Assim sugerimos que esta vocalização pode ser usada como uma ferramenta adicional para acessar o estado de bem-estar em capivaras.

On the relationships between ultrasonic calling and anxiety-related behavior in rats

In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala.