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 used temporal sequence effects in recognition memory tested 24 h 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 nonstressful c...

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 d, 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 ∼18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-positive, p-γH2AX-positive, an...

Rapid saccadic eye movements are used by animals to sample different parts of the visual scene. Previous work has investigated neural correlates of these saccades in visual cortical areas such as V1; however, how saccade-responsive neurons are distributed across visual areas, cell types, and cortical layers has remained unknown. Through analyzing 818 1 h experimental sessions from the Allen Brain Observatory, we present a large-scale analysis of saccadic behaviors in head-fixed mice and their neural correlates. We find that saccade-responsive neurons are present across visual cortex, but their distribution varies considerably by transgenically defined cell type, cortical area, and cortical layer. We also find that saccade-responsive neurons do not exhibit distinct visual response properties from the broader neural population, suggesting that the saccadic responses of these neurons are likely not predominantly visually driven. These results provide insight into the roles played by different cell types withi...

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...