As the European Flagship Human Brain Project (HBP) ends in September 2023, a meeting dedicated to the Partnering Projects (PPs), a collective of independent research groups that partnered with the HBP, was held on September 4–7, 2022. The purpose of this meeting was to allow these groups to present their results, reflect on their collaboration with the HBP and discuss future interactions with the European Research Infrastructure (RI) EBRAINS that has emerged from the HBP. In this report, we share the tour-de-force that the Partnering Projects that were present in the meeting have made in furthering knowledge concerning various aspects of Brain Research with the HBP. We describe briefly major achievements of the HBP Partnering Projects in terms of a systems-level understanding of the functional architecture of the brain and its possible emulation in artificial systems. We then recapitulate open discussions with EBRAINS representatives about the evolution of EBRAINS as a sustainable Research Infrastructure f...

Subjective uncertainty arises because the estimation of the timing of an event into the future is error prone. This impact of stimulus-bound uncertainty on movement preparation has often been investigated using reaction time tasks where a warning stimulus (WS) predicts the occurrence of a “go” signal. The timing of the “go” signal can be chosen from a particular probability distribution with a given variance or uncertainty. It has been repeatedly shown that reaction times covary with the shape of the used “go” signal distribution. This is interpreted as evidence for temporal preparation. Moreover, the variance of the response time should always increase with the duration of the delay between the WS and the “go” signal. This increasing variance has been interpreted as a consequence of the temporal “blurring” of future events (scalar expectancy). The present paper tested the validity of the temporal “blurring” hypothesis in humans with a simple oculomotor reaction time task where subjective and stimulus-boun...

Drug-induced taste disorders reduce quality of life, but little is known about the molecular mechanisms by which drugs induce taste disturbances. In this study, we investigated the short-term and long-term effects of the antiarrhythmic drug flecainide, which is known to cause taste dysfunction. Analyses of behavioral responses (licking tests) revealed that mice given a single intraperitoneal injection of flecainide exhibited a significant reduction in preference for a sour tastant (HCl) but not for other taste solutions (NaCl, quinine, sucrose, KCl and monopotassium glutamate) when compared with controls. Mice administered a single dose of flecainide also had significantly higher taste nerve responses to HCl but not to other taste solutions. Compared with controls, mice administered flecainide once-daily for 30 d showed a reduced preference for HCl without any changes in the behavioral responses to other taste solutions. The electrophysiological experiments using HEK293T cells transiently expressing otopet...

The spinal motor neurons are the only neural cells whose individual activity can be non-invasively identified. This is usually done using grids of surface electromyographic (EMG) electrodes and source separation algorithms; an approach called EMG decomposition. In this study, we combined computational and experimental analyses to assess how the design parameters of grids of electrodes influence the number and the properties of the identified motor units. We first computed the percentage of motor units that could be theoretically discriminated within a pool of 200 simulated motor units when decomposing EMG signals recorded with grids of various sizes and interelectrode distances (IED). Increasing the density, the number of electrodes, and the size of the grids, increased the number of motor units that our decomposition algorithm could theoretically discriminate, i.e., up to 83.5% of the simulated pool (range across conditions: 30.5-83.5%). We then identified motor units from experimental EMG signals recorde...

Understanding the neural basis of emotions is a critical step to uncover the biological substrates of neuropsychiatric disorders. To study this aspect in freely behaving mice, neuroscientists have relied on the observation of ethologically relevant bodily cues to infer the affective content of the subject, both in neutral conditions or in response to a stimulus. The best example of that is the widespread assessment of freezing in experiments testing both conditioned and unconditioned fear responses. While robust and powerful, these approaches come at a cost: they are usually confined within selected time windows, accounting for only a limited portion of the complexity of emotional fluctuation. Moreover, they often rely on visual inspection and subjective judgement, resulting in inconsistency across experiments and questionable result interpretations. To overcome these limitations, novel tools are arising, fostering a new avenue in the study of the mouse naturalistic behavior. In this work we developed a co...

While it is commonly assumed that stressful events are vividly remembered, it remains largely unknown whether all aspects of memory for a stressful episode are enhanced. In this preregistered study, we tested whether stress enhances later remembering of individual elements of a stressful episode at the cost of impaired processing of the association between these elements. Therefore, male and female participants (N=122) underwent a stressful (or control) episode during which they encoded a series of stimuli. To investigate stress effects on the memory for individual events and the links between these, we utilized temporal sequence effects in recognition memory tested 24 hours after encoding. Specifically, we tested whether stress would affect the memory enhancement for a target item if this is preceded by another item that also preceded the target during encoding (recognition priming). Our results showed that participants recalled single events encoded under stress better than those encoded under non-stress...

When a Pavlovian cue is presented separately from its associated reward, some animals will acquire a sign tracking (ST) response, approach and/or interaction with the cue, while others will acquire a goal tracking response, approach to the site of reward. We have previously shown that cue-evoked excitations in the nucleus accumbens (NAc) encode the vigor of both behaviors; in contrast, reward-related responses diverge over the course of training, possibly reflecting neurochemical differences between sign tracker and goal tracker individuals. However, a substantial subset of neurons in the NAc exhibit inhibitory, rather than excitatory, cue-evoked responses, and the evolution of their signaling during Pavlovian conditioning remains unknown. Using single-neuron recordings in behaving rats, we show that NAc neurons with cue-evoked inhibitions have distinct coding properties from neurons with cue-evoked excitations. Cue-evoked inhibitions become more numerous over the course of training and, like excitations, ...

To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Heinz et al., 2017; Jikomes et al., 2016), these tasks required different behavioral responses to each stimulus. As many brain regions involved in survival behavior process stimuli of opposite valence, we developed a paradigm in which mice perform the same response (nosepoke) to distinct auditory cues to obtain a rewarding outcome (palatable food) or avoid an aversive outcome (mild footshoock). This design allows for both within- and between-subject comparisons as animals respond to appetitive and aversive cues. The central nucleus of the amygdala (CeA) is implicated in the regulation of responses to stimuli of either valence. Considering its role in threat processing (H...

Neuropathic pain is stubborn and associated with peripheral nerve regeneration process. Nicotine has been found to reduce pain but whether it is involved in the regulation of nerve regeneration and the underlying mechanism are unknown. In this study, we examined the mechanical allodynia, thermal hyperalgesia together with the peripheral nerve regeneration after nicotine exposure in two rat neuropathic pain models. In the spinal nerve ligation (SNL) model, in which anatomical nerve regeneration can be easily observed, nicotine reduced anatomical measures of regeneration as well as expression of regeneration marker growth associated protein 43 (GAP43). In the tibial nerve crush model, nicotine treatment significantly suppressed GAP43 expression and functional reinnervation as measured by myelinated action potential and electromyography of gastrocnemius. In both models, nicotine treatment reduced macrophage density in the sensory ganglia and peripheral nerve. These effects of nicotine were reversed by the sel...

Stress alters social functioning in a complex manner. An important variable determining the final effects of stress is stressor intensity. However, the precise relationship between stressor intensity and social behavior is not well understood. Here we investigate the effects of varying acute stressor intensity exposure on social behavior using adult zebrafish. We first establish a novel test using adult zebrafish that allows distinguishing fish’s drive to approach a social cue and its ability to engage and maintain social interaction within the same behavioral paradigm. Next, we combined this test with a new method to deliver an acute stress stimulus of varying intensities. Our results show that both social approach and social maintenance are reduced in adult zebrafish upon acute stress exposure in an intensity-dependent manner. Interestingly, lower stress intensity reduces social maintenance without affecting the social approach, while a higher stress level is required to alter social approach. These resu...