One major hallmark of alcohol use disorder (AUD) is the persistence of drinking despite negative consequences. Among indicators of AUD vulnerability, binge drinking has been identified as one of the strongest risk factors. Although the lifetime prevalence of both binge drinking and AUD has historically been higher in men than women, this gap has dramatically narrowed in the last decade. Additionally, sex differences in AUD and binge drinking have been found in clinical and preclinical studies. At the neurobiological level, the insular cortex plays an important role in AUD, with the anterior (aIC) and posterior (pIC) divisions supporting different functions. However, the contributions of the aIC and pIC sections in sexual dimorphism of alcohol binge drinking and the persistence of alcohol drinking despite aversion remain to be uncovered. Using the drinking in the dark model in mice, we validated that female mice have a higher binge ethanol intake compared to males. To evaluate persistent ethanol consumption despite aversion, we supplemented ethanol with the bitter compound quinine, and found a higher persistent drinking in females compared to males. Using fiber photometry recordings, we revealed that aIC activity was increased during binge and persistent ethanol consumption independently of sex, whereas pIC glutamatergic neuron activity was higher during persistent ethanol drinking, specifically in female mice. Using chemogenetics, we revealed that inhibition of aIC glutamatergic neurons reduced intake of bitter solutions independently of the solvent (ethanol or water) in both sexes. In addition, inhibition of pIC glutamatergic neurons exclusively reduced persistent ethanol drinking in females, while decreasing quinine consumption only in males. These findings suggest a sex-dependent function of the pIC in the persistence of ethanol consumption, providing a starting point in understanding sex-specific functions of the insular cortex in the neurobiology of AUD.

BACKGROUND:Noxious stimuli are conveyed to and integrated in the dorsal horn of the spinal cord before being transmitted to supraspinal centres, where pain perception is generated. Descending pathways from the brainstem dynamically modulate this integration, either facilitating or inhibiting nociceptive information based on physiological, emotional, genetic and environmental factors. Serotonergic neurones in the nucleus raphe magnus (NRM), activating different spinal 5-hydroxytryptamine (5-HT) receptors, exert bidirectional control, both facilitatory and inhibitory, but the underlying mechanisms of this control remain unclear. METHODS:Serotonergic modulation by the NRM of nociception was investigated in adult mice using imaging, behavioural, pharmacological, electrophysiological, chemogenetic and optogenetic approaches. RESULTS:The action of serotonergic neurones in the NRM on spinal nociceptive transmission depends on their activation pattern, which targets different spinal 5-HT receptors likely associated with different spinal microcircuits. Serotonergic neurones of the NRM exert a tonic analgesic effect mediated by 5-HT2c receptor. Low increases in 5-HT activity led to increased analgesia through spinal inhibitory interneurones expressing 5-HT2c and 5-HT2A receptors. Prolonged stimulation of serotonergic neurones led to hyperalgesia mediated by 5-HT3 receptors. Comparison of 5-HT receptors in spinal tissue from mice and humans shows that 5-HT2c receptors have high expression level, comparable between both species. CONCLUSIONS:These results propose a bidirectional model of action by serotonin neurones of nociceptive transmission depending on their level of activity and show that 5-HT2c receptors mediate the serotonin-induced analgesia.

Social dysfunction is common in depression and varies with stress exposure and genetic risk. The current study identifies a cell-type specific role for Fkbp5, a glucocorticoid receptor co-chaperone, in noradrenergic neurons engaged during social stress. Acute social stress upregulated Fkbp5 in the locus coeruleus (LC), whereas repeated exposure attenuated this effect. Noradrenergic Fkbp5 deletion (Fkbp5Nat) increased pro-social behavior exclusively in male mice. In the basolateral amygdala (BLA), social interaction reduced norepinephrine (NE) turnover in wild-type but not Fkbp5Nat mice. Consistently, proteomics revealed mitochondrial/energy and synapse-related remodeling in BLA neurons. Miniscope imaging showed that behavior-locked NE transients in BLA were selectively blunted in Fkbp5Nat mice during interaction with outbred CD1 conspecifics, while same-strain C57BL/6N encounters preserved NE dynamics. Together, this study indicates that Fkbp5 tunes LC-BLA output to social salience in a sex- and context-dependent manner, suggesting a circuit-specific route to normalize social salience without broadly suppressing noradrenergic function. ### Competing Interest Statement The authors have declared no competing interest. Federal Ministry of Education and Research German Research Foundation, SCHM2360-5-1 European Union

The mechanism of action of serotonergic psychedelics is increasingly explored worldwide due to their clinical benefits in various psychiatric conditions. Beyond the stimulation of serotonin 2A (5-HT2A) receptors, psychedelics may desynchronize activity between brain regions, however the involvement of the corresponding neurotransmission systems has been largely overlooked. Given that monoaminergic systems target virtually all brain regions and play a role in exploratory behavior, we hypothesized that psychedelics disrupt the coherence of monoamine systems across brain regions during forced exploratory behavior in mice. Using post-mortem tissue quantification of serotonin (5-HT), dopamine (DA), noradrenaline (NA), and their metabolites in 28 distinct brain regions, we observed a dense and highly organized pattern of correlations within and between monoamines in vehicle-treated mice. This organization was disrupted by both the psychedelic 5-HT2A receptor agonist TCB-2 (0.3, 3 and 10 mg/kg) and the antagonist MDL-100,907 (0.2 mg/kg), both of which decreased correlations between regional neurochemical concentrations. Interestingly, the combination of MDL-100,907 and TCB-2 partially restored correlations. Quantitatively, TCB-2 dose-dependently decreased 5-HT turnover (metabolite/5-HT) across all brain regions, and DA turnover (3-methoxytyramine/DA) in the striatum. TCB-2 also enhanced markers of the DA and NA systems in certain brain regions, notably including the anterior cingulate cortex. MDL-100,907, which had minimal impact on monoamine levels when administered alone, reduced TCB-2 (3 mg/kg)-induced head twitches and increased monoamine concentrations in the anterior cingulate cortex, but did not affect the TCB-2-induced decrease 5-HT turnover across the brain. These data suggest that the functional connectivity of monoaminergic systems during exploration is highly sensitive to modulation through either activation or blockade of 5-HT2A receptors.

The insular cortex (or insula), and particularly its anterior region, plays a crucial role in the control of emotional valence and anxiety (Etkin & Wager, 2007; Mendez-Ruette et al., 2019; Nicolas et al., 2023). While dopamine neurotransmission is known to modulate anxiety levels in humans (Hjorth et al., 2021) and animal models (de la Mora et al., 2010; Bananej et al., 2012; Zarrindast & Khakpai, 2015; DeGroot et al., 2020; Godino et al., 2023), its regulatory effects on the anterior insula remained unexplored. Here, using a multifaceted approach, we uncovered how dopamine shapes anterior insula function in anxiety and valence processing. First, we revealed a high density of neurons expressing type-1 dopamine receptors (D1) in the insula, particularly important in the anterior insula, and seven times greater than the density of neurons expressing type-2 dopamine receptors (D2). Few neurons co-expressed Drd1 and Drd2 mRNAs in the anterior and posterior insula, and the density of Drd1+ neurons in the anterior insula was twice higher among inhibitory neurons than excitatory neurons. Second, we found that pharmacological activation of D1 in the anterior insula is anxiogenic, suggesting a direct link between insular dopamine signaling and anxiety-related behaviors. Using fiber-photometry recordings, we identified that the amplitude of dopamine release onto D1+ neurons in the anterior insula while mice were in anxiogenic spaces or receiving mild foot shocks was both positively correlated with mice level of trait anxiety. Population dynamics and deep-learning analyses of anterior insula single-unit recordings uncovered distinct coding patterns of anxiety-provoking and safe environments, as well as tastants of positive and negative valence. Remarkably, systemic D1 activation, which heightens anxiety-related behaviors, dampens this coding dichotomy by increasing coding variability for protected spaces while increasing the coding reliability for anxiogenic spaces. Interestingly, the coding reliability of anxiogenic areas was positively correlated with mice level of trait anxiety, and we observed a trend towards a positive correlation between the coding reliability of a negative tastants, and mice level of anxiety. Altogether, our findings provide a new model of neural population coding of anxiety and emotional valence and unravel D1-dependent coding mechanisms in the mouse anterior insula. ### Competing Interest Statement The authors have declared no competing interest.

Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the regulation of water intake. However, our understanding of the topographical, circuit, and molecular mechanisms for controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid (CB1) receptors in the insular cortex cells participate in the regulation of water intake and deconstructed the circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both the anterior insula (aIC) and posterior insula (pIC) increases in response to water intake, yet only the specific removal of CB1 receptors in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we recorded the neurons of the aIC or pIC targeting the BLA (aIC-BLA and pIC-BLA) and found that they decreased their activity upon water drinking. Additionally, chemogenetic activation of pIC-BLA projection neurons decreased water intake. Finally, we uncovered CB1-dependent short-term synaptic plasticity (depolarization-induced suppression of excitation [DSE]) selectively in pIC-BLA, compared with aIC-BLA synapses. Altogether, our results support a model where CB1 receptor signaling promotes water intake by inhibiting the pIC-BLA pathway, thereby contributing to the fine top-down control of thirst responses.

ABSTRACT BACKGROUND One major hallmark of alcohol use disorder (AUD) is the persistence of alcohol drinking despite negative consequences. Among the indicators of AUD vulnerability, binge drinking is a strong risk factor. Although the lifetime prevalence of binge and AUD has been historically higher in men than women, this gap dramatically narrowed in the last decade. Additionally, sex differences in AUD and binge drinking have been shown in clinical and preclinical studies, respectively. The insular cortex plays an important role in AUD, and the anterior (aIC) and posterior (pIC) divisions have dimorphic functions. However, the contributions of the aIC and pIC sections in alcohol binge drinking and alcohol persistent drinking despite aversion, as well as the sexual dimorphism of these contributions, remained to be uncovered. METHODS First, by combining the drinking in the dark model with chemogenetics, we studied the causal role of aIC and pIC excitatory neurons in binge and persistent ethanol drinking in C57BL6/J male (n=49) and female (n=49) mice. Second, using calcium fiber photometry, we investigated pIC neuronal activity in both sexes (male n=14, female n=11) during both binge and persistent ethanol drinking. RESULTS We identified a higher binge and persistent ethanol consumption in females compared to males. Chemogenetic inhibition of aIC glutamatergic neurons reduced bitter solutions intake independently of the solvent (ethanol or water), in both sexes. In contrast, inhibition of pIC glutamatergic neurons exclusively reduced persistent ethanol drinking in female mice. Finally, using fiber photometry recordings, we uncovered that pIC glutamatergic neuron activity was selectivity increased during ethanol persistent drinking in female mice. CONCLUSIONS These findings suggest a sex-dependent function of the pIC in persistent ethanol drinking, providing a starting point in our understanding of the insular cortex function in the neurobiology of AUD in both sexes.

The study of the mechanism of action of classical psychedelics has gained significant interest due to their clinical potential in the treatment of several psychiatric conditions, including major depressive and anxiety disorders. These drugs bind 5-hydroxytryptamine receptors (5-HTR) including 5-HT1AR, 5-HT2AR, 5-HT2BR, and/or 5-HT2CR, as well as other targets. 5-HTRs regulate the activity of ascending monoaminergic neurons, a mechanism primarily involved in the action of classical antidepressant drugs, antipsychotics, and drugs of abuse. Sparse neurochemical data have been produced on the control of monoaminergic neuron activity in response to classical psychedelics. Here we review the available data in order to determine whether classical psychedelics have specific neurochemical effects on serotonergic, dopaminergic, and noradrenergic neurons. The data show that these drugs have disparate effects on each monoaminergic system, demonstrating a complex response with state-dependent and region-specific effects. For instance, several psychedelics inhibit the firing of serotonergic neurons, although this is not necessarily associated with a decrease in serotonin release in all regions. Noradrenergic neuron spontaneous activity also appears to be inhibited by psychedelics, also not necessarily associated with a decrease in noradrenaline release in all regions. Psychedelics influence on dopaminergic systems is also complex as the above-mentioned 5-HTRs may have opposing effects on dopaminergic neuron activity, in a state-dependent manner. There is an apparent lack of clear neuronal signature induced by psychedelics on monoaminergic neuron activity despite specific recurrent mechanisms. This review provides a current summary of the action of psychedelics on monoamine neuromodulators serotonin, dopamine and noradrenaline, compiling reoccurring and contradictory findings demonstrating that a monoamine signature of psychedelics, if applicable, would be state- and region-dependant.

During periods of anxiety, the brain affects the heart, but does a racing heart also talk to the brain to cause anxiety-related behaviour? Use of a light-stimulated pacemaker in mice shows that it does, and pinpoints a brain region involved.

Academic training in neuroscience is an exciting and rich experience as it exposes us to a broad spectrum of fascinating scientific questions and cutting-edge techniques. However, as years of training pass, many feel a strong sense of disillusionment with the limited opportunities to pursue a career in the field they were so passionate about. This is especially true when it comes to postdoctoral positions. Postdoctoral training was originally defined as temporary employment after obtaining a doctorate during which a person could acquire/improve research skills, carry out mentoring and teaching activities and become scientifically independent in hope of landing a faculty position. Thus, unlike doctoral studies, postdoctoral appointments are not organized around a set of training objectives leading to a degree within a specific time frame. This lack of a structured framework often leads to the perception that postdoc is an ill-defined position. Multiple reports published over the past decades have shown that the lack of employment opportunities in academia for an increasing number of postdocs has created precarious situations for these early career researchers preventing them from progressing (Andalib et al., 2018; Cyranoski et al., 2011; DePaola & Kezar, 2017; Larson et al., 2014; Powell, 2015; Sauermann & Roach, 2016; Stephan, 2013). As junior faculty members, we have witnessed the departure of many of our talented colleagues after years of postdoctoral research. As they move away from their initial career choice, these researchers often find themselves facing a job market that is different from what they had prepared for during their academic training. For postdocs who are compelled to leave their field, the situation can be even more challenging as they approach potential employers with a sense of failure and overqualification, which can significantly diminish their chances of securing a job. We believe that the burden on postdoctoral researchers could be partly avoided if academic institutions and mentors provided better exposure to the breadth of neuroscience careers that can be undertaken after graduation. In this opinion piece, we first outline our perspective on current issues related to the career development of postdocs in training. We then present testimonials from neuroscientists who have embarked on exciting and diverse career paths. Our aim is to inspire and encourage the next generation of neuroscientists to take an active and continuous approach to their career development and to provide a more nuanced and multifaceted view of the career opportunities available in the field of neuroscience. From the moment they enter an academic institution, researchers are often mentored by faculty members with an academia-centric perspective on what professional fulfilment and success are. As trainees of the academic system, becoming a professor leading a research lab is generally presented as the only successful outcome. This notion is also reinforced by the limited availability of alternative role models, which can potentially narrow the range of career options for aspiring neuroscientists. This results in a biased view of the career landscape, potentially preventing the exploration of other fulfilling and meaningful career paths. Data collected over more than two decades at a leading European research institute in Biology (EMBL) revealed that only 22% of doctoral and 32% of postdoctoral researchers in that institution become principal investigators (PIs) in academia and that this percentage is decreasing over time (Lu et al., 2022; Woolston, 2022). Importantly, this study highlights the reality of diverse career paths in life science, including neuroscience. Tracking the professional development of former members of an institution provides invaluable insight for current and future generations, allowing them to appreciate the diverse opportunities and constraints of the job market and make informed decisions about their own career paths. In recent years, a growing number of graduate programs and academic institutions have begun exposing doctoral and postdoctoral fellows to existing and emerging career models, including opportunities in industry, science communication, science policy or outreach. Although the branching tree of career paths is slowly being integrated into mentorship and career development proposals, the language used to describe these trajectories still contributes to the academic bias, potentially limiting trainees' perception of career opportunities. Exclusive or diminishing phrases such as ‘alternative career’ or ‘outside academia’ should be reconsidered in favour of more inclusive formulae praising the diversity of career paths in neuroscience and their value to society. In this opinion piece, we refer to the ‘Neuroscience career landscape’ when discussing the range of career paths available to neuroscientists (Figure 1), avoiding a dichotomy based solely on academia. Although the postdoctoral position emerged after World War I in the United States to accelerate research in physics and chemistry, it did not become widespread and fully established in neuroscience until the second half of the 20th century (Committee to Review the State of Postdoctoral Experience in Scientists and Engineers [U.S.], 2014). Today, postdocs represent a major research workforce with a variety of professional responsibilities, including directing projects, mentoring students, delivering lectures and sometimes managing labs. Their growing number far exceeds the number of faculty positions that remains constant over time (Cyranoski et al., 2011; Larson et al., 2014; Main et al., 2021; Powell, 2015). Many of these reports have pointed to the simple mathematical problem behind these trends: there simply are not enough faculty positions for postdocs if they are all aiming for an academic career. As a result, postdoc stints that were initially intended to be short have become a state of limbo for many who are waiting for opportunities to advance their careers in academia. Additionally, the lack of clear milestones and objectives for these positions can potentially lead to situations where postdocs are treated as cheap and highly efficient labour that substitutes for teaching and administrative duties with the risk of slowing down their career development (Stephan, 2013). Unlike PIs, postdocs often lack the support of a union to help them navigate potential conflicts or violations of their contract terms, further adding to the precarious nature of their situation and lack of career oversight. Despite these constraints, the allure of pursuing their passion overpowers low wages, job instability and publication pressure, which are viewed as temporary obstacles they are willing to endure to secure their dream job. But for many, the postdoc is a default option that appears stable due to a lack of forethought about career development or misinformation about the prospects of succeeding in academia (Sauermann & Roach, 2016). This is understandable since the postdoc is an exciting phase in which one can conduct pioneering research in well-established laboratories without worrying about grant applications or other administrative burdens. However, postdoc positions have an expiration date. With the exception of a few postdocs who manage to extend their contract indefinitely (as long as their PI remains active), most postdocs find themselves seeking a stable job in a different sector after several years in academia. What exacerbates the situation is that gauging success has become progressively more challenging in recent years. Growing up in neuroscience, we often heard the dreadful saying: publish or perish. Now that we sit on hiring committees, it is disheartening to witness the rejection of candidates for faculty positions despite their exceptional track record, publications in top-tier journals and an exciting research project, all because of the overwhelming number of applicants. Unfortunately, we have transitioned to an academic system where you can publish, yet still perish. This anomalous competitive environment leads to the loss of talented neuroscientists, many of whom were trained with taxpayers' money. Consequently, it is crucial to explore potential systemic solutions to prevent talent drain in search of a future in neuroscience. We must provide early career researchers with greater exposure to the vast landscape of job opportunities in neuroscience and help them discover the path that best aligns with their ambitions and competencies. Since the first reports on issues with postdoc appointments emerged more than 50 years ago, numerous approaches have been proposed to alleviate the tensions in the academic system and promote diverse career models (Committee to Review the State of Postdoctoral Experience in Scientists and Engineers [U.S.], 2014; DePaola & Kezar, 2017; McDowell et al., 2014; Powell, 2015). Unfortunately, only a handful of recommendations have been put into action so far. We will not review them here, but will briefly touch on some ideas related to possible changes in the academic system that we believe would provide better prospects for scientists in training. Many institutions have implemented a guideline to restrict the number of years that postdocs can remain in their position. However, we believe that this policy has heightened the urgency for more comprehensive solutions to improve career development opportunities. A key challenge for postdocs is the lack of sustainable funding to support their work. To address this issue, many organizations worldwide have resorted to limiting the maximum number of postdoc years to encourage postdocs to enter the job market more quickly. However, such measures can have detrimental consequences as they foster short-sighted research strategies, curb creativity and increase pressure to publish hastily. Furthermore, postdocs often face difficulties in the publication process, which can extend beyond the institution's timeframe. While some senior PIs may find ways to retain postdocs past the time limit, such ‘permadoc’ positions tied to a specific PI are not a viable long-term solution as they leave postdocs jobless when their PI retires. Therefore, it is crucial for postdocs to take proactive steps to shape their career trajectories and achieve their professional goals before the countdown ends. Early career researchers are extensively trained, they excel in their field and easily adapt to diverse employment structures and countries. However, it is difficult for these scientists to assess the chances of success of a specific career path without having access to data on previous generations of researchers who have walked the same path. We believe that research institutions have two important responsibilities in this regard. First, they should inform their members about career opportunities based on the institution's track record, and second, they should help their employees plan their career development. This requires significant investment from research institutions to systematically track the career development of alumni. Formal collaborations with digital professional networks such as LinkedIn could be leveraged to facilitate tracking and public sharing of results. To enhance the prospects of success for early career members of research institutions, it is recommended to organize meetings or career fairs that bring together professionals from various fields of the neuroscience career landscape with the current institution. Additionally, the promotion of the track records of these early career researchers should be linked to such events to provide a comprehensive overview of their accomplishments and facilitate networking opportunities with potential employers (Diggs-Andrews et al., 2021). One solution to alleviate the pressure on postdocs is to integrate staff scientists into laboratories, as it is done in some countries such as France. This would reduce the number of postdocs recruited and encourage early career researchers to explore the neuroscience career landscape before entering the postdoctoral stage. Postdoc salaries are typically covered by individual researchers based on grants, making it extremely difficult, and often impossible, to stabilize their positions. Eliminating the precariousness and time limits of research stays in labs or institutions would allow researchers to develop richer projects, acquire more leadership and expertise and maintain crucial knowledge within laboratories. Institutions play a key role in this process, as they need to structure their long-term budgets to include one or more permanent researchers in each research lab, in addition to the principal investigator. Another interesting solution would be to redefine the postdoc position from a temporary appointment to a more recognized job status, such as ‘Research Scientist’. As neuroscience projects become more extensive and intricate, some research institutions are starting to adopt industry-like employment guidelines. By doing this conversion from postdoc position into research scientist role facilitates individuals to switch between jobs, without the fear of a set expiration date. In the same way that employees can move between companies without facing penalties, research scientists could build a solid track record by gaining experience in various laboratories driven by their passion rather than the fear of unemployment. Institutions would benefit from adopting a research structure with larger, interdisciplinary projects led by fewer principal investigators and featuring more research scientists within the teams. This approach would undoubtedly improve the conditions of early-career neuroscientists in training, who should be prioritized over scientific or economic outputs. One of the central challenges in Europe is to find a solution that is adaptable to the diverse range of research institutions, each with their own regional regulations. Any new rules implemented to improve the stability of researchers within the system should be standardized across European countries and, ideally, worldwide, to enable researchers to move freely for their training without jeopardizing their chances of reintegrating the job market in their home country. Such guidelines, shared between EU countries, would allow postdocs to benefit from professional recognition and continuous training, keeping them at the forefront of their field. Realistically, any effective solution that can enhance the working conditions and career prospects of postdocs will require time and may initially result in a decline in short-term productivity as pressure eases in the academic system. However, it would ultimately lead to greater long-term productivity and enable a more supportive environment for the scientists we train. By preventing prolonged exposure to stressful work environments, such measures could also mitigate the risk of mental health issues among postdocs. In an effort to expand the career horizons of early career scientists, we reached out to 8 professionals who have developed their profiles within the neuroscience career landscape. After kindly agreeing to participate in this opinion piece, we sent them 8 questions designed to frame the story of their career development (see below). We are very grateful to them for sincerely sharing their personal experiences, which we believe illustrate the diversity of life stories, but also the strong commonalities in their thoughts and approaches. Five testimonials are from scientists from different countries who started their own companies. This might seem out of reach to many trainees; however, it is important to note that national and local governments of several European countries, as well as the EU, offer start-up funding for innovative ideas. The experience reported hereafter is also an encouragement to seek for this support. These testimonials highlight in particular the quality of the academic training and its value in all sorts of job appointment. They also clearly show how important it is to have early exposure to these career paths and to actively seek information from professionals in different sectors of the neuroscience career landscape. We hope these testimonials will inspire neuroscientists in training to open their panel of opportunities for scientific growth. Questionnaire: 1) What is your current profession and what does it involve? 2) At what point in your career development did you decide to take this path and what motivated that decision? Did you think you were taking a risk? 3) Do you feel you had enough exposure and training in this profession before you started? 4) Do you think your former academic institutions played a positive role in shaping your career path? What could have been improved? 5) Where did you find the strongest support? 6) How did you experience stepping away from an academic career path? 7) Are you satisfied with your current position? Do you think it offers enough stability and challenges? Do you ever have second thoughts about your choice to pursue this career? 8) What advice would you give to the next generation of neuroscientists to help them find their career path? I currently work at SynDiag, a company that I co-founded in 2018 together with two other scientists. We use artificial intelligence to spot ovarian cancer from ultrasound images. Our products are software that support doctors during daily examinations. I work as Chief Technology Officer which means I coordinate technology-related activities to provide a product that responds to customer needs. I also develop software parts and write code very often. Before founding SynDiag, I completed a PhD in visual neuroscience and started a postdoc because I felt that as a forced path. PIs never discussed alternative options, alumni were not invited to talk about their alternative careers, and finding a postdoc position was relatively simple. After three years, I realized I lacked the motivation to insist on papers, positions abroad and short-term fellowships. The effort was no longer compensated by the pleasure in doing research. I started looking for other opportunities, until I met my co-founders and got involved in this new project. A startup seemed as risky as pursuing another postdoc position in terms of job stability, but it gave me the opportunity to work on something with a clear start and final objective and to grow professionally. The startup offered challenges, the opportunity to keep doing research and to use state-of-the-art technology. It also gives the opportunity to fill a non-academic CV that can be then used to land on a more traditional and stable industry job. My decision was welcomed by friends and colleagues, but my family gave the greatest support by helping me through almost two years without salary. When we started the company I mainly worked on R&D projects. To me it was very similar to academia where my work required designing experiments, supervising the research activity and the students collaborating, deciding next steps according to data; all skills that could be transferred to a R&D, or data science, company job. I learnt the rest on the job. In my experience, the difficulty in transition was twofold. Academic training already provided competences that could be translated to an industry job, but I was not aware of them. I missed the jargon to express them and some skills, e.g. project management and teamwork. Industry jobs require several checkpoints and milestones to ensure that a project is worth the investment. This means working on a tight schedule and having to sacrifice promising but not sustainable projects. Teamwork also has a different approach to academia: although there's a clear lead, accountability is shared and the team is directed toward the same goal. This for me determined a completely new way to work. To other neuroscientists, I would suggest getting to know startups and companies working in similar topics. Also starting research projects in collaboration with industrial partners could benefit both sides: on the one hand, companies get access to data and can co-author patents and publications; on the other hand, research groups can better understand industry needs and share costs and resources. Interacting a lot with people from different backgrounds, sharing different points of view, being curious about other people's jobs does help getting acquainted with the difference in approach. And at least it will help build the jargon to better express what we can do and what we are looking for. I am a Research Scientist at Hoffmann-La Roche, where I have three main roles. As a Research Project Leader, I organize teams of experts with the goal of bringing potential new therapies into the clinic. As the Systems Neuroscience Section Head, I facilitate the work of four laboratories focused on understanding how drug candidates work on the brain. As a Lab Head within the Section, I coordinate research activities focused on in vivo electrophysiology to support many programs across neuroscience and rare diseases. I joined Roche after an academic path that started at the University of Barcelona and took me through the University of Edinburgh and MIT, among others. Academic colleagues and mentors taught me how to identify and address critical questions. However, towards the end of my postdoc, I knew I wanted to ‘climb a different mountain’ than the paths that academia offered. Industry and biotech appeared new and exciting with the edge of hopefully impacting the lives of patients. The risks were clear as ‘leaving academia’ is usually a one-way door. I had no training whatsoever in the inner workings of Industry. Nevertheless, the professions of scientist, critical thinker and data generator and evaluator require similar skills regardless of career. My former academic institutions played a very positive role in shaping my career path. Academic mentors and colleagues shaped me as a leader and contributor as I was fortunate to learn from and publish with the best. Later, in Industry, I had to discover some skillsets that academic institutions never taught me. The strongest support for my career transition came from my new home, Roche. There is a clear understanding in this company that developing internal talent is a priority. Since day one I have had access to training and mentorship. Previous to the ‘jump’ into Industry, I never found an organized opportunity to learn about the many worlds outside academia. I had to enquire by informally talking to others who had made that transition. I never had regrets about stepping away from an academic career, and at the same time, I felt impostor syndrome for breakfast, lunch and dinner. It took me a while to find my way as it felt like switching from playing Chess to playing Go, but I have no second thoughts about my career choice. I am lucky to experience the best of both worlds and I am becoming comfortable with the pace of change. My advice to the next generation of Neuroscientists would be to first, introspectively think about ‘what value do you bring’. Your value relates to, but is not the same as your skills, and is what one builds a career around. Be aware that value is assessed both with offer and demand factors. Every company is different: there is more diversity between startups, biotechs and companies than between academic institutions. Second, ‘decide when to switch’. The longer you wait, the harder it will be to find an opening. Also, imagine the daily and weekly routine that the forty- and fifty-year-old ‘you’ will want to live. Work backwards from that time commitment to your job into the design of career paths that take you there. I would also advise you to do internships in your local biotech or Pharma Company. Finally, networking: obviously, talk to your contacts that made the transition and invest in your digital profiles, including LinkedIn profile. I am a Technical and Commercial Manager at Scientifica Ltd, a company manufacturing electrophysiology and multiphoton imaging systems for the neuroscience community. I work closely with our global sales team to help configure and quote systems to meet our customer's varied application needs. I coordinate with our supply chain to ensure we have the best prices for our customers and the company and also with engineering to continuously improve and develop our products. During my undergraduate degree, I enjoyed the practical lab aspects of my dissertation project but couldn't see myself doing it day in and day out, and the prospect of funding application cycles just wasn't for me. At the time, I didn't know anyone else moving into a commercial business, but I am very glad I made the step. Scientifica has supported and trained me every step of the way, and I now feel like I am still involved in supporting neuroscience research but in a way that suits my own skills and personal life. My neuroscience degree from Sussex University gave me the perfect background to understand our customers' research and application needs, and the additional training for specific aspects of my role have been provided as I have needed them. Whilst most of the university career advice was aimed towards continuing a profession in research, my supervisor suggested Scientifica as a local company specializing in neuroscience and assisted me in my application. I have no second thoughts so far! My role has changed and progressed over my time at Scientifica as I have gained experience and learnt which aspects I enjoy and excel at. I value the security and support that a position in a commercial company offers, whilst enjoying the variety and different puzzles which come up day to day within my role. My advice to the next generation of neuroscientists to help them find their career path is to think about what you enjoy doing, what is important to you in a job and how this may fit with your personal life. Work experience days can be really helpful to see how a role may suit you and what it is like in practice instead of just on paper. I am the founder and director of a small company called Independent NeuroScience Services (INSS). We started in 2016, and we provide consulting services and bespoke hardware for neuroscience research labs, primarily in the field of multiphoton microscopy. I did a couple of postdoc stints and then decided to ‘leave academia’ when I realized that I wasn't cut out for it. Some people thrive in high-octane environments and the competitive pressure spurs them on to do their best work. Good on them. But this frantic lifestyle doesn't suit everyone. It just didn't seem conducive to my performance and my job satisfaction. I can work and think better when clarity and serenity prevail. Leaving academia didn't feel like a risky move at all. I didn't have a new job lined up, but I was very optimistic that some interesting opportunity would emerge eventually. I never had a problem finding a job when I needed one. To name a few, I've been a skiing instructor in the Bavarian Alps and I worked as a junior doctor in a psychiatry hospital. I've developed software and performed in a bluegrass band at festivals across Europe. All those different jobs came to me by serendipity rather than by career planning, and I was always confident that my propensity for odd-jobbing and good fortune would see me through. I had a very good grasp of multiphoton microscopy and related neuroscience techniques. But I knew nothing about project management, or accounting, or manufacturing. You can learn all of that on the job. I wouldn't say that academic institutions played a role in shaping my career path. As a student or postdoc, my horizon was mostly the lab and the people in it, plus the friends and collaborators of the lab. I was lucky to work with great colleagues and PIs, and those experiences shaped my career path. But I attribute this to the specific individuals involved, not the institutions. I have had a lot of encouragement from my academic colleagues and peers, as well as from my wife and my parents. Moving away from an academic career was basically like moving to a foreign country. It's a fun learning experience to try and orient oneself in a different culture and acclimatize to its idiosyncrasies. I'm very satisfied with my current position, and I never had any second thoughts about leaving academia. I get to travel a lot and meet very interesting and inspiring people, including many of my former colleagues and peers. And I work on technically challenging projects that are still closely related to academic research. I use an extremely simplistic algorithm: ‘Follow your nose. If it feels right, it probably is. If it doesn't feel right, cut your losses and move on.’ That worked nicely for me, but your mileage may vary. Everyone's circumstances are different, so each person has to clarify for themselves which connotations the term ‘career path’ should entail. From my personal perspective, I'd like to interpret ‘career path’ as a lifelong dance. Maybe a Lindy Hop. Or pogo. As the Governor's Director of Precision Medicine, I lead the California Initiative to Advance Precision Medicine, oversee cross-sector health policy working groups and projects and administer research grantmaking and state government interagency efforts. I regularly work with fellow government officials at the state and federal levels, academic researchers, community advocacy organizations and patient advocates, health care providers, industry and venture capital representatives and think tanks, among others. I always had a sense that science needed more ‘bridge people’ to shepherd knowledge to action, but I didn't learn about the term science policy until graduate school. Throughout my years in academia, I was heavily involved in extracurricular activities that cantered on community service. While conducting experim