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...

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, ...

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...

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...

Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal degeneration. This work investigates the effects of excessive TH signaling on photoreceptor function and survival in mice. C57BL/6, Thra1-/- , Thrb2-/- , Thrb-/- , and the cone dominant Nrl-/- mice received triiodothyronine (T3) treatment (5-20 µg/ml in drinking water) for 30 days, followed by evaluations of retinal function, photoreceptor survival/death, and retinal stress/damage. Treatment with T3 reduced light responses of rods and cones by 50-60%, compared with untreated controls. Outer nuclear layer thickness and cone density were reduced by about 18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-, p-γH2AX-, and 8-OHdG-...

Previous research has questioned whether motor adaptation is shaped by an optimal combination of multisensory error signals. Here, we expanded on this work by investigating how the use of visual and somatosensory error signals during online correction influences single-trial adaptation. To this end, we exposed participants to a random sequence of force-field perturbations and recorded their corrective responses as well as the after-effects exhibited during the subsequent unperturbed movement. In addition to the force perturbation we artificially decreased or increased visual errors by multiplying hand deviations by a gain smaller or larger than one. Corrective responses to the force perturbation clearly scaled with the size of the visual error, but this scaling did not transfer one-to-one to motor adaptation and we observed no consistent interaction between limb and visual errors on adaptation. However, reducing visual errors during perturbation led to a small reduction of after-effects and this residual i...

One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wildtype (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2-/- mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when compa...

When movements become inaccurate, the resultant error induces motor adaptation to improve accuracy. This error-based motor learning is regarded as a cerebellar function. However, the influence of the other brain areas on adaptation is poorly understood. During saccade adaptation, a type of error-based motor learning, the superior colliculus (SC) sends a post-saccadic error signal to the cerebellum to drive adaptation. Since the SC is directly inhibited by the substantia nigra pars reticulata (SNr), we hypothesized that the SNr might influence saccade adaptation by affecting the SC error signal. In fact, previous studies indicated that the SNr encodes motivation and motivation influences saccade adaptation. In this study, we first established that the SNr projects to the rostral SC, where small error signals are generated, in non-human primates. Then, we examined SNr activity while the animal underwent adaptation. SNr neurons paused their activity in association with the error. This pause was shallower and ...