The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next. Critically, mice were required to actively nose-poke in order to exploit a given site. We show that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increases the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function.

Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions.DOI: http://dx.doi.org/10.7554/eLife.20975.001

Objectives To identify differences in letters of recommendation (LORs) of applicants to a single ophthalmology residency program by gender, race, academic performance, and match outcome. Design This was a retrospective analysis of LORS for 2,523 applicants (7,569 letters) to the University of California, Irvine ophthalmology residency program from 2011 to 2018. Methods Programming scripts were employed to determine the number of times 22 key words from four thematic categories (standout words, ability, grindstone, and compassion) appeared in LORs for each applicant. A chi-square test was performed to assess for possible differences in the presence of each key word by the following characteristics: gender, underrepresented minority (URM) status, Alpha Omega Alpha (AOA) membership, the United States Medical Licensing Exam (USMLE) Step 1 score, and match outcome. Linear regressions were created to determine the frequency at which words in each thematic category appeared according to the same baseline characteristics. Results In the LORs, females were more likely to be described as “empathetic” (p = 0.002), URMs were more likely to be described as “caring” (p = 0.002), high Step 1 scorers (≥240) were more likely to be described as “outstanding” (p = 0.002), and matched students were more likely to be described as “exceptional” (p = 0.001), “outstanding” (p < 0.001), and “superb” (p = 0.001). Standout words appeared more often in the LORs of AOA members, matched candidates, and high Step 1 scorers (p < 0.001 for all comparisons). “Competent” appeared more commonly in LORs for low Step 1 scorers (p < 0.001) and unmatched applicants (p = 0.001). Conclusion This study identifies differences in LORs by gender, URM status, and achievement including successful ophthalmology residency match. Females and URMs were more likely to be described as “empathetic” and “caring,” respectively; otherwise, we detected no gender or racial disparities in key word use in LORs. Candidates with high USMLE Step 1 scores or AOA membership had a higher frequency of standout words in their LORs. Whether they were truly more qualified in various dimensions or if they benefited from a halo effect bias warrants further investigation. There was a significant difference in the number of standout words in LORs between matched and unmatched applicants, suggesting that key word frequency may be a relevant metric for LOR appraisal.

The neuromodulator serotonin (5-HT) has been implicated in a variety of functions that involve patience or impulse control. For example, activation of 5-HT neurons promotes waiting for delayed rewards. Many of these effects are consistent with a long-standing theory that 5-HT promotes behavioral inhibition, a motivational bias favoring passive over active behaviors. To further test this idea, we studied the impact of 5-HT in a probabilistic foraging task, in which mice must learn the statistics of the environment and infer when to leave a depleted foraging site for the next.Critically, mice were required to actively nose poke in order to exploit a given site. We found that optogenetic activation of 5-HT neurons in the dorsal raphe nucleus increased the willingness of mice to actively attempt to exploit a reward site before giving up. These results indicate that behavioral inhibition is not an adequate description of 5-HT function and suggest that a unified account must be based on a higher-order function.Serotonin (5-HT) is a central neuromodulator that is implicated in the regulation of many processes and is one of the most important targets of psychoactive drugs 1,2 . As a unifying concept for 5-HT's manifold effects, Soubrié 3 put forward the hypothesis that a major function of 5-HT is to promote behavioral inhibition. Building on work showing that blockade of serotonin transmission results in continued responses to stimuli that are no longer rewarding 4-7 , he argued that in situations wherein animals face a decision between active response and passivity, higher levels of 5-HT would bias the decision in favor of the latter.3 More recently, the study of 5-HT and behavioral inhibition has concentrated chiefly on impulse control 8-10 . One of the most common tasks used to study impulsive behavior is the five-choice serial reaction time task (5-CSRTT), in which rodents are required to respond to visual stimuli to obtain rewards 11 . Although this task was not specifically designed to measure impulsivity, animals sometimes respond prematurely (i.e. before stimulus presentation), a behavior indicative of impulsivity. Consistent with the idea that 5-HT promotes patience, alterations such as brain-wide 5-HT depletion increase impulsivity in this task 12 .Another line of experiments focuses on animals' ability to wait in order to obtain reward 13 .Electrophysiological recordings from the dorsal raphe nucleus (DRN; the major source of serotonin to the forebrain) in rats trained to wait for delayed rewards have found that most of these neurons increase their firing rates during waiting 14 . Moreover, pharmacological blocking of these neurons by the local application of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) locally into the DRN promotes premature leaving 14 , whereas optogenetic activation of the same neurons promotes patience 15,16 .All of these results are still broadly consistent with the Soubrié theory of behavioral inhibition. By reducing the motivation to act, increased se...

The adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain. The transplantation of embryonic interneurons has been shown to restore juvenile plasticity to the adult host visual cortex. It is unclear whether transplanted interneurons directly mediate the renewed cortical plasticity or whether these cells act indirectly by modifying the host interneuron circuitry. Here we find that the transplant-induced reorganization of mouse host circuits is specifically mediated by Neuregulin (NRG1)/ErbB4 signaling in host parvalbumin (PV) interneurons. Brief visual deprivation reduces the visual activity of host PV interneurons but has negligible effects on the responses of transplanted PV interneurons. Exogenous NRG1 both prevents the deprivation-induced reduction in the visual responses of host PV interneurons and blocks the transplant-induced reorganization of the host circuit. While deletion of ErbB4 receptors from host PV interneurons blocks cortical plasticity in the transplant recipients, deletion of the receptors from the donor PV interneurons does not. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating the function of host PV interneurons.