Dorsal raphe dopamine neurons represent the experience of social isolation

The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area dopamine (VTA DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic a ctivation of DRN DA neurons increases social preference, but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank , together supporting a role for DRN dopamine neurons in mediating a loneliness-like state

Listening to mental health crisis needs at scale: using Natural Language Processing to understand and evaluate a mental health crisis text messaging service

The current mental health crisis is a growing public health issue requiring a large-scale response that cannot be met with traditional services alone. Digital support tools are proliferating, yet most are not systematically evaluated, and we know little about their users and their needs. Shout is a free mental health text messaging service run by the charity Mental Health Innovations, which provides support for individuals in the UK experiencing mental or emotional distress and seeking help. Here we study a large data set of anonymised text message conversations and post-conversation surveys compiled through Shout. This data provides an opportunity to hear at scale from those experiencing distress; to better understand mental health needs for people not using traditional mental health services; and to evaluate the impact of a novel form of crisis support. We use natural language processing (NLP) to assess the adherence of volunteers to conversation techniques and formats, and to gain insight into demographic user groups and their behavioural expressions of distress. Our textual analyses achieve accurate classification of conversation stages (weighted accuracy = 88%), behaviours (1-hamming loss = 95%) and texter demographics (weighted accuracy = 96%), exemplifying how the application of NLP to frontline mental health data sets can aid with post-hoc analysis and evaluation of quality of service provision in digital mental health services

nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta

GABA neurons in the VTA and SNc play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several target regions including the nucleus accumbens. It is not clear whether some of these GABA neurons are dedicated local interneurons or if they all collateralize and send projections externally as well as making local synaptic connections. Testing between these possibilities has been challenging in the absence of interneuron-specific molecular markers. We hypothesized that one potential candidate might be neuronal nitric oxide synthase (nNOS), a common interneuronal marker in other brain regions. To test this, we used a combination of immunolabelling (including antibodies for nNOS that we validated in tissue from nNOS-deficient mice) and cell type-specific virus-based anterograde tracing in mice. We found that nNOS-expressing neurons, in the parabrachial pigmented (PBP) part of the VTA and the SNc were GABAergic and did not make detectable projections, suggesting they may be interneurons. In contrast, nNOS-expressing neurons in the rostral linear nucleus (RLi) were mostly glutamatergic and projected to a number of regions, including the lateral hypothalamus (LH), the ventral pallidum (VP), and the median raphe (MnR) nucleus. Taken together, these findings indicate that nNOS is expressed by neurochemically- and anatomically-distinct neuronal sub-groups in a sub-region-specific manner in the VTA and SNc