Application Of Serotonin Research Articles

Exogenous application of serotonin, with the modulation of redox homeostasis and photosynthetic characteristics, enhances the drought resistance of the saffron plant

Water stress is one of the most significant abiotic stresses that disrupts the osmotic balance of plants and consequently reduces their growth and performance. In recent years, it has been found that serotonin, as a signaling and regulatory molecule, can play important roles in the growth and development of plants and enhance their tolerance to abiotic stresses. Saffron is a plant known for its medicinal and culinary properties. Its distinct flavor, aroma, and vibrant color make it a sought-after ingredient in various cuisines and traditional medicines. The aim of this study is to investigate the possible effect of serotonin growth regulator on some morphophysiological and biochemical characteristics of saffron plant under water stress conditions. Water stress was applied using polyethylene glycol 6000 at a level of 30%, w/v. Serotonin was also applied exogenously at a concentration of 100 µM in both foliar and root applications. The experimental findings demonstrated that water stress had a detrimental impact on various growth and photosynthetic parameters including FW, DW, SH, RWC, photosynthetic pigments content, Pn, Fv/Fm, C and Ci. Under these conditions, H2O2 content and ion leakage increased. The increase in the content of proline and sugars also confirmed that the saffron plant was placed in unfavorable growth conditions. Serotonin application in both foliar and root applications and especially root treatment under stressful conditions improved plant growth by activating enzymatic and non-enzymatic antioxidant systems. Overall, the exogenous application of serotonin increased the resistance of saffron plants to water stress.

Ablation of CD44 Attenuates Adipogenesis in White Adipocytes via the Tryptophan 5-Hydroxylase 2/5-Hydroxytryptamine Axis to Protect Mice from High-Fat Diet–Induced Obesity

CD44 is a transmembrane protein that plays an essential role in transducing extracellular stimuli into intracellular signaling cascades especially in cancer cells. Recent studies have shown that CD44 contributes to metabolic regulation. However, the effect of CD44 on adipogenesis in white adipose tissue (WAT) remains unclear. Here, the results showed that the expression of CD44 was largely increased in the inguinal and epididymal WAT of obese mice. Ablation or neutralization of CD44 inhibits adipogenesis in cultured adipocytes. CD44 deficient mice are resistant to high-fat diet (HFD) induced obesity and metabolic dysfunction. RNA-seq, together with functional studies, revealed that reduced expression of tryptophan 5-hydroxylase 2 (Tph2) in WAT is responsible for the repressed adipogenesis in the absence of CD44. The application of 5-hydroxytryptamine (5-HT), a product of TPH2, rescues the repressed adipogenesis induced by CD44 neutralization. Moreover, the inhibition of TPH2 by p-chlorophenylalanine (pCPA) recapitulates the beneficial phenotypes observed in CD44 deficient mice. Taken together, these data indicate that CD44 plays a pivotal role in adipogenesis in WAT. In this regard, CD44 and its downstream target TPH2 may hold great therapeutic potential for treating excessive adiposity-related metabolic disorders such as obesity, insulin resistance, and type 2 diabetes.

Serotonin application to Guizotia abyssinica improves growth, physiological functions, antioxidant system and alleviates the deleterious effects induced by salt stress

Serotonin is a well-known animal hormone and ubiquitous monoamine. In recent years, its presence in plants has attracted the attention of many researchers. In plants, serotonin as signaling hormone plays a pivotal role in hormonal crosstalk, regulating antioxidant metabolism and developmental processes under abiotic stresses. Among abiotic stresses, salt stress considerably influences Guizotia abyssinica growth and physio-chemical functions. The effect of exogenous serotonin was assessed to ameliorate the harmful effect of salinity stress at different levels. All the growth parameters, chlorophyll pigments, gas exchange indicators, and nitrate reductase activity were decreased under all salinity levels while 2-thiobarbituric acid reactive substances (TBARS), proline, and antioxidant activities were increased. Serotonin improved the length of roots and shoots, basal diameter, leaf number, area, width and length, root dry matter, stem dry matter, leaves dry matter, chlorophyll a, chlorophyll b, chlorophyll fluorescence, transpiration rate, stomatal conductance, photosynthetic rate, relative water content, water use efficiency, and nitrate reductase under salt stress condition. Moreover, the upregulation of antioxidant enzymes evoked by the salt stress was further enhanced. Taken together, salt stress inhibited the growth and performance of G. abyssinica, however, exogenous application of serotonin fortified its tolerance by mitigating membrane damage and improving assimilatory functions, plant water status and plant defense metabolism, thereby lowering the adverse effects of salt stress on various plant growth performance and physio-biochemical functions.

Correlation between Neurotransmitters (Dopamine, Epinephrine, Norepinephrine, Serotonin), Prognostic Nutritional Index, Glasgow Prognostic Score, Systemic Inflammatory Response Markers, and TNM Staging in a Cohort of Colorectal Neuroendocrine Tumor Patients.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Spontaneous intersibling polymorphism in the development of dopaminergic neuroendocrine cells in sea urchin larvae: impacts on the expansion of marine benthic species.

The plasticity of the nervous system plays a crucial role in shaping adaptive neural circuits and corresponding animal behaviors. Understanding the mechanisms underlying neural plasticity during development and its implications for animal adaptation constitutes an intriguing area of research. Sea urchin larvae offer a fascinating subject for investigation due to their remarkable evolutionary and ecological diversity, as well as their diverse developmental forms and behavioral patterns. We conducted immunochemical and histochemical analyses of serotonin-containing (5-HT-neurons) and dopamine-containing (DA-positive) neurons to study their developmental dynamics in two sea urchin species: Mesocentrotus nudus and Paracentrotus lividus. Our approach involved detailed visualization of 5-HT- and DA-positive neurons at gastrula-pluteus stages, coupled with behavioral assays to assess larval upward and downward swimming in the water column, with a focus on correlating cell numbers with larval swimming ability. The study reveals a heterochronic polymorphism in the appearance of post-oral DA-positive neuroendocrine cells and confirms the stable differentiation pattern of apical 5-HT neurons in larvae of both species. Notably, larvae of the same age exhibit a two- to four-fold difference in DA neurons. An increased number of DA neurons and application of dopamine positively correlate with larval downward swimming, whereas 5-HT-neurons and serotonin application induce upward swimming. The ratio of 5-HT/DA neurons determines the stage-dependent vertical distribution of larvae within the water column. Consequently, larvae from the same generation with a higher number of DA-positive neurons tend to remain at the bottom compared to those with fewer DA-positive neurons. The proportion of 5-HT and DA neurons within larvae of the same age underlies the different potentials of individuals for upward and downward swimming. A proposed model illustrates how coordination in humoral regulation, based on heterochrony in DA-positive neuroendocrine cell differentiation, influences larval behavior, mitigates competition between siblings, and ensures optimal population expansion. The study explores the evolutionary and ecological implications of these neuroendocrine adaptations in marine species.

Serotonin excites medial olivocochlear neurons of the auditory efferent pathway

Medial olivocochlear (MOC) efferent neurons are located in the superior olive of the brainstem and form a sound evoked feedback loop that inhibits cochlear amplification via suppression of outer hair cell (OHC) electromotility. MOC neurons putatively receive a diverse range of synaptic input from various auditory and non-auditory brain regions. Given the proposed role of these neurons in context dependent tasks such as selective attention, we are interested in investigating the non-auditory modulation of MOC activity by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). We used the ChAT-IRES-Cre;tdTomato mouse model to identify cholinergic MOC neurons in the brainstem. Immunohistochemical data have validated serotonergic terminals in apposition to both retrogradely labeled and genetically identified MOC neurons in mouse. During patch-clamp recordings from MOC neurons, exogenous application of serotonin increased neuron excitability by increasing action potential (AP) firing rate and decreasing both rheobase and AP threshold. Additionally, serotonin reduced the stimulation required to evoke a given AP firing rate in MOC neurons. These data will aid in our understanding of central auditory processing and how factors such as mood and attention are involved in modulating MOC responses in complex listening situations such as in the presence of background noise.

Differences in responses of premotor interneurons to serotonin and 5-hydroxytryptophan, a precursor for serotonin synthesis, in naive and trained snails

This study investigated the responses of premotor interneurons LPa3 and RPa3 of the snails to applications of serotonin and 5-hydroxytryptophan (5-HTP), a precursor for serotonin synthesis, as ingredients of the broth that bathes the central nervous system of naive snails and snails after the formation of long-term sensitization. Measurements of the electrical characteristics have shown that a membrane potential of interneurons LPa3 and RPa3 in naive snails was significantly depolarized (3.7 mV) in the presence of serotonin, while the threshold potential was increased (unsupported hypothesis). The similar pattern was observed in the presence of 5-hydroxytryptophan: true depolarization to 3.1 mV occurred in interneurons until reaching the unreliable rise in the threshold potential inducing an action potential. It was found that application of serotonin causes a significant decrease in the membrane potential of interneurons LPa3 and RPa3 of trained snails (depolarization to 4.6 mV) and the unreliable increase in the threshold potential of premotor interneurons (0.9 mV). In contrast, application of 5-hydroxytryptophan causes an unreliable increase (2.5 mV) of the membrane potential and also an unreliable increase (0.8 mV) in the threshold potential.

Exogenous serotonin improves drought and salt tolerance in tomato seedlings

Serotonin and melatonin, which are indolamines present in every biological kingdom, show strong bioregulator activity in plant tissues under various stress conditions. Although numerous studies have reported the stress mitigating effects of melatonin, the effect of serotonin on plant stress physiology has rarely been studied in the current literature. In this study, the effects of exogenous serotonin application on tomato seedlings under severe salt and drought stresses were investigated by examining various morphological and physiological plant stress indicators, including tissue length and mass, relative water content (RWC), ion leakage, malonedialdehyde (MDA) and proline content, as well as some oxidative stress related gene activities, ascorbate peroxidase (APX1), superoxide dismutase (FeSOD), catalase (CAT2), glutathione reductase (GR1), delta 1-pyrroline-5-carboxylate synthase (P5CS) and 1-aminocyclopropane-1-carboxylic acid synthase 2 (ACS2). Our results showed that the tissue MDA contents decreased by 29% and 18%, the ion leakage levels decreased by 39% and 34%, whereas the relative water contents increased by 22% and 18%, respectively, under salt and drought stresses upon serotonin application. Serotonin also decreased ACS2 gene expression by 28% and 70%, while increasing FeSOD by 69 and 17%, CAT2 by 145 and 110% and GR1 gene expression by 67 and 22%, respectively, under salt and drought stresses. Also, the transcript level of P5CS increased 48% under serotonin salt coapplication. Our findings showed that similar to its close chemical relative melatonin, serotonin also exhibits stress mitigation effects and boosts the antioxidant capacity of tomato plants under most common abiotic stress conditions.

Serotonergic modulation of local network processing in V1 mirrors previously reported signatures of local network modulation by spatial attention.

Sensory processing is influenced by neuromodulators such as serotonin, thought to relay behavioural state. Recent work has shown that the modulatory effect of serotonin itself differs with the animal's behavioural state. In primates, including humans, the serotonin system is anatomically important in the primary visual cortex (V1). We previously reported that in awake fixating macaques, serotonin reduces the spiking activity by decreasing response gain in V1. But the effect of serotonin on the local network is unknown. Here, we simultaneously recorded single-unit activity and local field potentials (LFPs) while iontophoretically applying serotonin in V1 of alert monkeys fixating on a video screen for juice rewards. The reduction in spiking response we observed previously is the opposite of the known increase of spiking activity with spatial attention. Conversely, in the local network (LFP), the application of serotonin resulted in changes mirroring the local network effects of previous reports in macaques directing spatial attention to the receptive field. It reduced the LFP power and the spike-field coherence, and the LFP became less predictive of spiking activity, consistent with reduced functional connectivity. We speculate that together, these effects may reflect the sensory side of a serotonergic contribution to quiet vigilance: The lower gain reduces the salience of stimuli to suppress an orienting reflex to novel stimuli, whereas at the network level, visual processing is in a state comparable to that of spatial attention.

Characterizing the Mechanism of Serotonin Alleviates Rice Resistance to Brown Planthopper Nilaparvata lugens (Homoptera: Delphacidae) Nymphs

Serotonin is a well-known secondary metabolite that plays an important role in many growth and developmental processes, as well as biotic and abiotic stress responses of plants. Yet, whether serotonin biosynthesis regulates the resistance of rice to the brown planthopper (BPH) Nilaparvata lugens and its underling mechanisms have not been entirely investigated. In this study, we found that expression levels of four serotonin biosynthesis gene, OsTDC1, OsTDC2, OsTDC3, and OsT5H, and the serotonin content were significantly induced by BPH nymph infestation. The rice seedlings pretreated with serotonin were more attractive to BPH nymphs and promoted their feeding behavior as indicated by increased honeydew excretion. In addition, serotonin application to artificial diets increased the survival rates of BPH nymphs in a dose-dependent manner compared to the controls. Moreover, the exogenous serotonin application to rice seedlings increased the average injury scale and functional plant loss indices caused by BPH nymph infestation. Moreover, supplemented serotonin enhanced soluble sugar and free amino acid contents, as well as the activities of SOD, POD, and PPO, but repressed the production of flavonoids. Our findings illustrated that serotonin plays a negative role in the regulation of rice resistance to BPH nymphs probably by modulating contents of soluble sugars, free amino acids, and flavonoids.

Contribution of histone acetylation to the serotonin-mediated long-term synaptic plasticity in terrestrial snails.

Serotonin plays a decisive role in long-term synaptic plasticity and long-term memory in mollusks. Previously, we demonstrated that histone acetylation is a regulatory mechanism of long-term memory in terrestrial snail. At the behavioral level, many studies were done in Helix to elucidate the role of histone acetylation and serotonin. However, the impact of histone acetylation on long-term potentiation of synaptic efficiency in electrophysiological studies in Helix has been studied only in one paper. Here we investigated effects of serotonin, histone deacetylases inhibitors sodium butyrate and trichostatin A, and a serotonergic receptor inhibitor methiothepin on long-term potentiation of synaptic responses in vitro. We demonstrated that methiothepin drastically declined the EPSPs amplitudes when long-term potentiation was induced, while co-application either of histone deacetylase inhibitors sodium butyrate or trichostatin A with methiothepin prevented the weakening of potentiation. We showed that single serotonin application in combination with histone deacetylase blockade could mimic the effect of repeated serotonin applications and be enough for sustained long-lasting synaptic changes. The data obtained demonstrated that histone deacetylases blockade ameliorated deficits in synaptic plasticity induced by different paradigms (methiothepin treatment, the weak training protocol with single application of serotonin), suggesting that histone acetylation contributes to the serotonin-mediated synaptic plasticity.

Chronic-Exposure Low-Frequency Magnetic Fields (Magnetotherapy and Magnetic Stimulation) Influence Serum Serotonin Concentrations in Patients with Low Back Pain-Clinical Observation Study.

(1) Background: The influence of serotonin on many regulatory mechanisms has not been sufficiently studied. The use of a physical method, assuming the possibility of its action on increasing the concentration of serotonin, may be the direction of therapy limiting the number of antidepressants used. The aim of the research was to study the effects of low-frequency magnetic fields of different characteristics on the circadian profile of serotonin in men with low back pain. (2) Methods: 16 men with back pain syndrome participated in the study. The patients were divided into two groups. In group 1, magnetotherapy (2.9 mT, 40 Hz, square wave, bipolar) was applied at 10.00 a.m. In group 2, the M2P2 magnetic stimulation program of the Viofor JPS device was used. Treatments in each group lasted 3 weeks, 5 days each, with breaks for Saturday and Sunday. The daily serotonin profile was determined the day before the exposure and the day after the last treatment. Blood samples (at night with red light) were collected at 8:00, 12:00, 16:00, 24:00, and 4:00. The patients did not suffer from any chronic or acute disease and were not taking any medications. (3) Results: In group 1, a significant increase in serotonin concentration was observed after 15 treatments at 4:00. In group 2, a significant increase in serotonin concentration was observed at 8:00 after the end of the treatments. In comparison between magnetotherapy and magnetic stimulation, the time points at which differences appeared after the application of serotonin occurred due to the increase in its concentrations after the application of magnetic stimulation. (4) Conclusions: Magnetotherapy and magnetic stimulation, acting in a similar way, increase the concentration of serotonin. Weak magnetic fields work similarly to the stronger ones used in TMS. It is possible to use them in the treatment of mental disorders or other diseases with low serotonin concentrations.

Alleviation of the Germination Inhibitory Effect of Salt Stress in Pepper (Capsicum annuum L.) Seeds by Serotonin

Salinity stress is one of the important factors affecting all growth processes, from seed germination to seedling development, plant growth, yield and quality. In this study, the effects of serotonin treatments on the germination of pepper seeds (Capsicum annum L.) under salt stress were investigated. Different doses of salt (0, 75 and 150 mM NaCl) and serotonin (S0:0 µM, S1:5 µM, S2:10 µM, S3:15 µM, S4: 20 µM) were used. The applied seeds were placed between the papers in petri dishes, watered with the prepared salt solutions and left to germinate at 25 °C. In the study, parameters related to germination percentage, germination speed, mean germination time, daily mean germination time, peak value and germination value were investigated. As a result of the research, it was determined that the germination of pepper seeds decreased in parallel with increasing salt concentrations, and this negative effect of salt stress decreased with serotonin applications. Although it changes depending on the serotonin doses, it has been observed that significant effects occur on the measured germination parameters, and the best germination was observed at S1 and S2 doses. It is thought that the application of serotonin will have positive effects on the germination of pepper seeds under salt stress, and these effects may also occur during the plant growth period.

Role of serotonin in modulating the development and function of adult-born neurons in the olfactory bulb.

Role of serotonin in modulating the development and function of adult-born neurons in the olfactory bulb.

Analyses of the Mode of Action of an Alpha-Adrenoceptor Blocker in Substantia Gelatinosa Neurons in Rats.

To elucidate why naftopidil increases the frequency of spontaneous synaptic currents in only some substantia gelatinosa (SG) neurons, post-hoc analyses were performed. Blind patch-clamp recording was performed using slice preparations of SG neurons from the spinal cords of adult rats. Spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs, respectively) were recorded. The ratios of the frequency and amplitude of the sIPSCs and sEPSCs following the introduction of naftopidil compared with baseline, and after the application of naftopidil, serotonin (5-HT), and prazosin, compared with noradrenaline (NA) were evaluated. First, the sIPSC analysis indicated that SG neurons reached their full response ratio for NA at 50 μM. Second, they responded to 5-HT (50 μM) with a response ratio similar to that for NA, but prazosin (10 μM) did not change the sEPSCs and sIPSCs. Third, the highest concentration of naftopidil (100 μM) led to two types of response in the SG neurons, which corresponded with the reactions to 5-HT and prazosin. These results indicate that not all neurons were necessarily activated by naftopidil, and that the micturition reflex may be regulated in a sophisticated manner by inhibitory mechanisms in these interneurons.

Antidromic Spike Propagation and Dissimilar Expression of P2X, 5-HT, and TRPV1 Channels in Peripheral vs. Central Sensory Axons in Meninges.

Background: The terminal branches of the trigeminal nerve in meninges are supposed to be the origin site of migraine pain. The main function of these peripheral sensory axons is the initiation and propagation of spikes in the orthodromic direction to the second order neurons in the brainstem. The stimulation of the trigeminal ganglion induces the release of the neuropeptide CGRP in meninges suggesting the antidromic propagation of excitation in these fibers. However, the direct evidence on antidromic spike traveling in meningeal afferents is missing.Methods: By recording of spikes from peripheral or central parts of the trigeminal nerve in rat meninges, we explored their functional activity and tested the expression of ATP-, serotonin-, and capsaicin-gated receptors in the distal vs. proximal parts of these nerves.Results: We show the significant antidromic propagation of spontaneous spikes in meningeal nerves which was, however, less intense than the orthodromic nociceptive traffic due to higher number of active fibers in the latter. Application of ATP, serotonin and capsaicin induced a high frequency nociceptive firing in peripheral processes while, in central parts, only ATP and capsaicin were effective. Disconnection of nerve from trigeminal ganglion dramatically reduced the tonic antidromic activity and attenuated the excitatory action of ATP.Conclusion: Our data indicate the bidirectional nociceptive traffic and dissimilar expression of P2X, 5-HT and TRPV1 receptors in proximal vs. distal parts of meningeal afferents, which is important for understanding the peripheral mechanisms of migraine pain.

Ингибитор гистондеацитилаз усиливает долговременную синаптическую потенциацию в нейронах виноградной улитки

Recently, substantial amount of data was accumulated in the literature suggesting an important role of epigenetics in formation of long-term synaptic plasticity - the main cellular mechanism of learning and memory. In this work, we studied the effect of inhibition of histone deacetylases, one of the types of epigenetic modifications, on the formation of long-term potentiation of synaptic responses in premotor (command) neurons of the avoidance behavior of the grape snail. Potentiation of synaptic inputs in these neurons underlies aversive memory in this animal. We showed that histone deacetylase inhibitor sodium butyrate increases the amplitude of long-term potentiation caused by five tetanizations of the sensory nerve, combined with application of serotonin. We also found that application of sodium butyrate by itself caused an increase in EPSP amplitude 4 hours after application. However, this increase cannot underlie the observed effect of long-term potentiation, which was observed throughout the experiment. Thus, in our work, we have demonstrated the role of histone modifications in long-term changes in synaptic plasticity.

Layer-specific serotonergic induction of long-term depression in the prefrontal cortex of rats.

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 μM) induced activity-dependent long-term depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT2 receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca2+ chelation. The 5-HT2 receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor-dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

Serotonergic Modulation of Sensory Neuron Activity and Behavior in Apteronotus albifrons.

Organisms must constantly adapt to changes in their environment to survive. It is thought that neuromodulators such as serotonin enable sensory neurons to better process input encountered during different behavioral contexts. Here, we investigated how serotonergic innervation affects neural and behavioral responses to behaviorally relevant envelope stimuli in the weakly electric fish species Apteronotus albifrons. Under baseline conditions, we found that exogenous serotonin application within the electrosensory lateral line lobe increased sensory neuron excitability, thereby promoting burst firing. We found that serotonin enhanced the responses to envelope stimuli of pyramidal cells within the lateral segment of the electrosensory lateral line lobe (ELL) by increasing sensitivity, with the increase more pronounced for stimuli with higher temporal frequencies (i.e., >0.2 Hz). Such increases in neural sensitivity were due to increased burst firing. At the organismal level, bilateral serotonin application within the ELL lateral segment enhanced behavioral responses to sensory input through increases in sensitivity. Similar to what was observed for neural responses, increases in behavioral sensitivity were more pronounced for higher (i.e., >0.2 Hz) temporal frequencies. Surprisingly, a comparison between our results and previous ones obtained in the closely related species A. leptorhynchus revealed that, while serotonin application gave rise to similar effects on neural excitability and responses to sensory input, serotonin application also gave rise to marked differences in behavior. Specifically, behavioral responses in A. leptorhynchus were increased primarily for lower (i.e., ≤0.2 Hz) rather than for higher temporal frequencies. Thus, our results strongly suggest that there are marked differences in how sensory neural responses are processed downstream to give rise to behavior across both species. This is even though previous results have shown that the behavioral responses of both species to envelope stimuli were identical when serotonin is not applied.

Serotonin modulates optimized coding of natural stimuli through increased neural and behavioural responses via enhanced burst firing.

The function of serotonergic fibres onto sensory areas remains poorly understood We show that serotonin application enhances sensory neural and behavioural responses to second order stimuli Enhanced neural responses most likely occurred because of increased burst firing Changes in neural sensitivity due to burst firing were the best predictor of changes in behavioural sensitivity Our results suggest that serotonin optimizes coding of stimuli encountered during aggression. Understanding how the processing of sensory information leads to behavioural responses remains a central problem in systems neuroscience. Here, we investigated how the neuromodulator serotonin affects neural and behavioural responses to second-order envelope stimuli within the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We found that serotonin application increased neuronal excitability through greater tendency for burst firing. We found that increased excitability led to overall higher neural sensitivities to higher envelope frequencies. Separating the spike train into bursts and isolated spike train components revealed that this was due to significant increases in neural sensitivity for the former but not the latter. We next investigated the consequences of such changes in sensitivity towards optimized coding of stimuli with specific statistics. Our results show that serotonin application compromised optimal coding of stimuli with statistics seen under naturalistic conditions due to changes in burst, but not isolated spike firing. Finally, we found that serotonin application increased behavioural sensitivity to envelope stimuli. Interestingly, changes in neural sensitivity due to bursts were a far better predictor of changes in behavioural sensitivity, suggesting that burst firing is decoded by downstream brain areas. Overall, our results suggest that serotonin modulates neural responses to optimize coding and perception of stimuli during behavioural contexts associated with encountering dominant conspecifics.