Social Behavior In Rats Research Articles

Long-term diabetic hyperglycaemia modifies social behaviour in rats

Diabetes is a known risk factor for cognitive decline and mood disorders. However, the effects of long-term diabetic hyperglycaemia on the various dimensions of social behaviours, such as play or aggression, remains to be fully elucidated. In this study, we evaluated the social behaviour in a nicotinamide-streptozotocin rat model of long-term diabetic hyperglycaemia, in the absence of glucose-lowering treatments. Five months following induction of hyperglycaemia, we scored affiliative/exploratory or aggressive social interactions between pairs of unacquainted rats in a neutral arena. Our results demonstrate alterations in the behaviour of long-term diabetic rats faced with social novelties. Specifically, diabetic hyperglycaemic rats engaged in hyper-sociable and hyper-aggressive encounters. Interestingly, social interactivity was not associated with the degree of hyperglycaemia in affiliative/exploratory or in aggressive social interactions, in our long-term diabetic rat model. Altogether, our data suggest a lack of social appropriateness in long-term diabetic hyperglycaemic rats which is independent of the degree of hyperglycaemia. These findings support the importance of a tight glycaemic control in the management of diabetes at every stage of the disease and enlighten the importance of impaired glycaemic control as a novel metabolic player impacting the neural networks of social behaviours.

R-Baclofen Treatment Corrects Autistic-like Behavioral Deficits in the RjIbm(m):FH Fawn-Hooded Rat Strain.

The Fawn-hooded rat has long been used as a model for various peripheral and central disorders and the data available indicate that the social behavior of this strain may be compromised. However, a thorough description of the Fawn-hooded rat is unavailable in this regard. The objective of the present study was to investigate various aspects of the Fawn-hooded rat's social behavior in depth. Our results show that several facets of socio-communicational behavior are impaired in the RjIbm(m):FH strain, including defective ultrasonic vocalizations in pups upon maternal deprivation, reduced social play in adolescence and impaired social novelty discrimination in adulthood. In addition, Fawn-hooded rats exhibited heightened tactile sensitivity and hyperactivity. The defects observed were comparable to those induced by prenatal valproate exposure, a widely utilized model of autism spectrum disorder. Further on, the pro-social drug R-baclofen (0.25-1 mg/kg) reversed the autistic-like defects observed in Fawn-hooded rats, specifically the deficiency in ultrasonic vocalization, tactile sensitivity and social novelty discrimination endpoints. In conclusion, the asocial, hypersensitive and hyperactive phenotype as well as the responsivity to R-baclofen indicate this variant of the Fawn-hooded rat strain may serve as a model of autism spectrum disorder and could be useful in the identification of novel drug candidates.

Study of the effect of phosphorylated carboxylic acids new derivatives on the main behavioral disorders in rats in the valproate model of autism

BACKGROUND: Due to the increasing frequency of autism in the population, the complexity of behavioral symptoms, and the need for long-term therapy, it is important to find new safe drugs for the correction of behavioral disorders.
 AIM: Studying the possibility of correcting behavioral changes characteristic of autism in rats in the valproate model of autism using new derivatives of phosphorylated carboxylic acids.
 MATERIAL AND METHODS: The possibility of correcting behavioral disorders in male and female rats in the valproate model of autism was studied with intraperitoneal administration (7 days) of new derivatives from the group of phosphorylated acetohydrazides (B2, C5) and thiosemicarbazide (T8) in doses of 1/100 LD50 on behavioral tests “Elevated Plus Maze”, “Burying Balls”, “Extended Open Field”. Statistical processing was carried out in the GraphPad prism 8.0.1 program using Student's t-test.
 RESULTS: It was found that the most pronounced anxiolytic effect on rats with autism was exerted by the compound 2-[(diphenylphosphoryl)acetyl]-N-phenylhydrazine-1-carbothioamide (T8), increasing by 4.8 times (p=0.033) in females and 4.4 times (p=0.036) in males, the time they spent in open arms in the “Elevated Plus Maze” test. The corrective effect on social behavior in rats with autism was most noted for T8 and B2 [2-ethoxy-2-oxoethanammonium salt (2-ethoxy-2-oxotyl) phenylphosphinic acid], which was characterized by an increase in the time spent with a social object (unfamiliar rat) 6.4 times (p=0.04) and 5.2 times (p=0.039), respectively, in the “Extended open field” method. When assessing the behavior of rats in the valproate model of autism in the “Burying Balls” test, it was found that the use of B2, T8 and C5 reduced the level of stereotypy, reducing the number of buried balls by 1.7 times (p=0.009), 1.5 times (p=0.046 ) and 1.7 times (p=0.011), respectively, compared to rats in the valproate model of autism without treatment.
 CONCLUSION: Derivatives of phosphorylated acetohydrazides and thiosemicarbazide have an anxiolytic effect, correct disturbances in social behavior and reduce the severity of stereotypic behavior in rats in the valproate model of autism.

Effects of ketamine on rat social behavior as analyzed by DeepLabCut and SimBA deep learning algorithms.

Traditional methods of rat social behavior assessment are extremely time-consuming and susceptible to the subjective biases. In contrast, novel digital techniques allow for rapid and objective measurements. This study sought to assess the feasibility of implementing a digital workflow to compare the effects of (R,S)-ketamine and a veterinary ketamine preparation Vetoquinol (both at 20mg/kg) on the social behaviors of rat pairs. Historical and novel videos were used to train the DeepLabCut neural network. The numerical data generated by DeepLabCut from 14 video samples, representing various body parts in time and space were subjected to the Simple Behavioral Analysis (SimBA) toolkit, to build classifiers for 12 distinct social and non-social behaviors. To validate the workflow, previously annotated by the trained observer historical videos were analyzed with SimBA classifiers, and regression analysis of the total time of social interactions yielded R 2 = 0.75, slope 1.04; p < 0.001 (N = 101). Remarkable similarities between human and computer annotations allowed for using the digital workflow to analyze 24 novel videos of rats treated with vehicle and ketamine preparations. Digital workflow revealed similarities in the reduction of social behavior by both compounds, and no substantial differences between them. However, the digital workflow also demonstrated ketamine-induced increases in self-grooming, increased transitions from social contacts to self-grooming, and no effects on adjacent lying time. This study confirms and extends the utility of deep learning in analyzing rat social behavior and highlights its efficiency and objectivity. It provides a faster and objective alternative to human workflow.

Deep learning algorithms reveal increased social activity in rats at the onset of the dark phase of the light/dark cycle.

The rapid decrease of light intensity is a potent stimulus of rats' activity. The nature of this activity, including the character of social behavior and the composition of concomitant ultrasonic vocalizations (USVs), is unknown. Using deep learning algorithms, this study aimed to examine the social life of rat pairs kept in semi-natural conditions and observed during the transitions between light and dark, as well as between dark and light periods. Over six days, animals were video- and audio-recorded during the transition sessions, each starting 10 minutes before and ending 10 minutes after light change. The videos were used to train and apply the DeepLabCut neural network examining animals' movement in space and time. DeepLabCut data were subjected to the Simple Behavioral Analysis (SimBA) toolkit to build models of 11 distinct social and non-social behaviors. DeepSqueak toolkit was used to examine USVs. Deep learning algorithms revealed lights-off-induced increases in fighting, mounting, crawling, and rearing behaviors, as well as 22-kHz alarm calls and 50-kHz flat and short, but not frequency-modulated calls. In contrast, the lights-on stimulus increased general activity, adjacent lying (huddling), anogenital sniffing, and rearing behaviors. The animals adapted to the housing conditions by showing decreased ultrasonic calls as well as grooming and rearing behaviors, but not fighting. The present study shows a lights-off-induced increase in aggressive behavior but fails to demonstrate an increase in a positive affect defined by hedonic USVs. We further confirm and extend the utility of deep learning algorithms in analyzing rat social behavior and ultrasonic vocalizations.

The Role of Corticotropin-Releasing Factor (CRF) and CRF-Related Peptides in the Social Behavior of Rodents.

Since the corticotropin-releasing factor (CRF) was isolated from an ovine brain, a growing family of CRF-related peptides has been discovered. Today, the mammalian CRF system consists of four ligands (CRF, urocortin 1 (Ucn1), urocortin 2 (Ucn2), and urocortin 3 (Ucn3)); two receptors (CRF receptor type 1 (CRF1) and CRF receptor type 2 (CRF2)); and a CRF-binding protein (CRF-BP). Besides the regulation of the neuroendocrine, autonomic, and behavioral responses to stress, CRF and CRF-related peptides are also involved in different aspects of social behavior. In the present study, we review the experiments that investigated the role of CRF and the urocortins involved in the social behavior of rats, mice, and voles, with a special focus on sociability and preference for social novelty, as well as the ability for social recognition, discrimination, and memory. In general, these experiments demonstrate that CRF, Ucn1, Ucn2, and Ucn3 play important, but distinct roles in the social behavior of rodents, and that they are mediated by CRF1 and/or CRF2. In addition, we suggest the possible brain regions and pathways that express CRF and CRF-related peptides and that might be involved in social interactions. Furthermore, we also emphasize the differences between the species, strains, and sexes that make translation of these roles from rodents to humans difficult.

High-Resolution Descriptions of Social Behavior in Rats and Their Deficits in Genetic Models of ASD

High-Resolution Descriptions of Social Behavior in Rats and Their Deficits in Genetic Models of ASD

Brief postnatal exposure to bisphenol A affects apoptosis and gene expression in the medial prefrontal cortex and social behavior in rats with sex specificity

Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure. Because an increased number of neurons in the PFC is a characteristic of a subtype of autism spectrum disorder, we tested social preference following brief BPA exposure and also expression of a small group of genes. Males and females were exposed to BPA from postnatal days (P) 6 through 8 or from P10 through 12. Both exposures significantly decreased indicators of cell death in the developing medial prefrontal cortex in male subjects only. Additionally, males exposed to BPA from P6 – 8 showed decreased social preference and decreased cortical expression of Shank3 and Homer1, two synaptic scaffolding genes that have been implicated in social deficits. There were no significant effects of BPA in the female subjects. These results draw attention to the negative consequences following brief exposure to BPA during early development.

Tryptophan Hydroxylase 2 Knockout Male Rats Exhibit a Strengthened Oxytocin System, Are Aggressive, and Are Less Anxious.

The central serotoninergic system is critical for stress responsivity and social behavior, and its dysregulations have been centrally implicated in virtually all neuropsychiatric disorders. Genetic serotonin depletion animal models could provide a tool to elucidate the causes and mechanisms of diseases and to develop new treatment approaches. Previously, mice lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing altered behaviors and neurotransmission. However, the effect of congenital serotonin deficiency on emotional and social behavior in rats is still largely unknown, as are the underlying mechanisms. In this study, we used a Tph2 knockout (Tph2–/–) male rat model to study how the lack of serotonin in the rat brain affects anxiety-like and social behaviors. Since oxytocin is centrally implicated in these behaviors, we furthermore explored whether the effects of Tph2 knockout on behavior would relate to changes in the oxytocin system. We show that Tph2–/– rats display reduced anxiety-like behavior and a high level of aggression in social interactions. In addition, oxytocin receptor expression was increased in the infralimbic and prelimbic cortices, paraventricular nucleus, dorsal raphe nucleus, and some subregions of the hippocampus, which was paralleled by increased levels of oxytocin in the medial frontal cortex and paraventricular nucleus but not the dorsal raphe nucleus, central amygdala, and hippocampus. In conclusion, our study demonstrated reduced anxiety but exaggerated aggression in Tph2–/– male rats and reveals for the first time a potential involvement of altered oxytocin system function. Meanwhile, the research of oxytocin could be distinguished in almost any psychiatric disorder including anxiety and mental disorders. This research potentially proposes a new target for the treatment of such disorders, from a genetic serotonin deficiency aspect.

Effects of Treadmill Exercise on Social Behavior in Rats Exposed to Thimerosal with Respect to the Hippocampal Level of GluN1, GluN2A, and GluN2B.

Thimerosal (THIM) kills brain neurons via induction of apoptosis and necrosis and induces the pathological features of autism spectrum disorder (ASD) in rats. THIM also affects the function of glutamatergic receptors. On the other hand, exercise induces both improvement and impairment effects on memory, depending on intensity, type, and duration. Treadmill exercise can also alter the expression of glutamatergic receptors. In this study, we aimed to investigate the effect of THIM and three protocols of treadmill exercise on social interaction memory and hippocampal expression of GluN1, GluN2A, and GluN2B in rats. THIM was injected intramuscularly at the dose of 300µg/kg. The three-chamber apparatus was used to evaluate social interaction memory, and western blotting was used to assess protein expression. The results showed that THIM impaired social memory. Exercise 1 impaired social affiliation in controls. Social memory was impaired in all exercise groups of controls. Exercise 1 + 2 impaired social affiliation in THIM rats. Social memory was impaired in all groups of THIM rats. Exercises 2 and 1 + 2 decreased the expression of GluN1, and exercise 1 increased the expression of GluN2A and GluN2B in controls. THIM increased the expression of GluN2B, while exercise 1 reversed this effect. All exercise protocols increased the expression of GluN2A, and exercises 2 and 1 + 2 increased the expression of GluN1 in THIM rats. In conclusion, both THIM and exercise impaired social memory. Of note, the results did not show a separate and influential role for glutamatergic subunits in modulating memory processes following THIM injection or exercise.

Infant ultrasonic vocalizations predict adolescent social behavior in rats: Effects of early life adversity.

Early life adversity (ELA) increases risk for psychopathologies that often manifest during adolescence and involve disrupted social functioning. ELA affects development of the prefrontal cortex (PFC), which plays a role in social behavior. PFC oxytocin and vasopressin are important regulators of, first, mother-infant attachment, and, later, social behavior, and are implicated in psychiatric disorders. Here, we tested whether infant social communication is predictive of PFC development and adolescent social behavior. We used the limited bedding (LB) ELA model in rats during postnatal days (P)2-14, and measured isolation-induced ultrasonic vocalizations (USVs) at P10 to characterize differences in an early social response. Rats were tested for dyadic social interaction in adolescence (P34). Adolescent oxytocin receptor (Oxtr) and arginine-vasopressin receptor 1a mRNA were measured in the PFC. Relationships between infant USVs, adolescent behavior, and gene expression were assessed. LB-reared rats exhibited fewer USVs at P10. While social behaviors were not robustly affected by rearing, fewer total and complex-type infant USVs predicted fewer interactions in adolescence. LB increased Oxtr in both sexes but Oxtr was not directly predicted by USVs. Findings support the use of USVs as indicators of differential early life experience in rodents, toward further characterization of early factors associated with vulnerability.

Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning.

All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors based on evidence of their vulnerability to direct or ancestral exposures, together with their importance in reproduction and survival of a species. Using a novel “two hits, three generations apart” experimental rat model, we investigated interactions of two classes of EDCs across six generations. PCBs (a weakly estrogenic mixture Aroclor 1221, 1 mg/kg), Vinclozolin (antiandrogenic, 1 mg/kg) or vehicle (6% DMSO in sesame oil) were administered to pregnant rat dams (F0) to directly expose the F1 generation, with subsequent breeding through paternal or maternal lines. A second EDC hit was given to F3 dams, thereby exposing the F4 generation, with breeding through the F6 generation. Approximately 1200 male and female rats from F1, F3, F4 and F6 generations were run through tests of sociability and social novelty as indices of social preference. We leveraged machine learning using DeepLabCut to analyze nuanced social behaviors such as nose touching with accuracy similar to a human scorer. Surprisingly, social behaviors were affected in ancestrally exposed but not directly exposed individuals, particularly females from a paternally exposed breeding lineage. Effects varied by EDC: Vinclozolin affected aspects of behavior in the F3 generation while PCBs affected both the F3 and F6 generations. Taken together, our data suggest that specific aspects of behavior are particularly vulnerable to heritable ancestral exposure of EDC contamination, that there are sex differences, and that lineage is a key factor in transgenerational outcomes.

P.0044 Memantine improves social behavior in rats exposed prenatally to valproic acid

When brachytherapy doses are reported or added, biologically effective dose (BED) minimum dose covering 90% of the volume (D90) is used as if dose is delivered uniformly to the target. Unlike BED(D90), equivalent uniform BED (EUBED) and generalized biologically equivalent uniform dose (gBEUD) are quantities that integrate dose inhomogeneity. Here we compared BED(D90) and equivalent uniform BED (EUBED)/gBEUD in 3 settings: (1) 2 sites using tandem and ovoid (T&O) but different styles of implants; (2) 2 sites using different devices—T&O and tandem and ring (T&R)—and different styles; and (3) the same site using T&O and T&R with the same style.EUBED and gBEUD were calculated for 260 fractions from 3 institutions using BED(α/β = 10 Gy). EUBED uses an extra parameter α with smaller values associated with radioresistant tumors. Similarly, gBEUD uses a, which places variable emphasis on hot/cold spots. Distributions were compared using the Kolmogorov-Smirnoff test at 5% significance.For the 2 sites using T&O, the distribution of EUBED-BED(D90) was not different for values of α = 0.5 to 0.3 Gy−1 but was statistically different for values of α = 0.15 to 0.05 Gy−1 (P=.01, .002). The mean percentage differences between EUBED and BED(D90) ranged from 20% to 100% for α = 0.5 Gy−1 to 0.05 Gy−1. Using gBEUD-BED(D90), the P values indicate the distributions to be similar for a = −10 but to be significantly different for other values of a (−5, −1, 1). Between sites and at the same site using T&O versus T&R, the distributions were statistically different with EUBED/gBEUD irrespective of parameter values at which these quantities were computed. These differences indicate that EUBED/gBEUD capture differences between the techniques and applicators that are not detected by the BED(D90).BED(D90) is unable to distinguish between plans created by different devices or optimized differently. EUBED/gBEUD distinguish between dose distributions created by different devices and styles of implant and planning. This discrepancy is particularly important with the increased use of magnetic resonance imaging and hybrid devices, whereby one has the ability to create dose distributions that are significant departures from the classic pear.

Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala

Social interaction deficits seen in psychiatric disorders emerge in early-life and are most closely linked to aberrant neural circuit function. Due to technical limitations, we have limited understanding of how typical versus pathological social behavior circuits develop. Using a suite of invasive procedures in awake, behaving infant rats, including optogenetics, microdialysis, and microinfusions, we dissected the circuits controlling the gradual increase in social behavior deficits following two complementary procedures-naturalistic harsh maternal care and repeated shock alone or with an anesthetized mother. Whether the mother was the source of the adversity (naturalistic Scarcity-Adversity) or merely present during the adversity (repeated shock with mom), both conditions elevated basolateral amygdala (BLA) dopamine, which was necessary and sufficient in initiating social behavior pathology. This did not occur when pups experienced adversity alone. These data highlight the unique impact of social adversity as causal in producing mesolimbic dopamine circuit dysfunction and aberrant social behavior.

A mixture of diethylhexyl, diisononyl and dibutyl phthalate decreased anogenital distance, postnatal testosterone levels, and changed social behavior in Wistar rats.

Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

Ketamine anesthesia enhances fear memory consolidation via noradrenergic activation in the basolateral amygdala

Trauma patients treated with ketamine during emergency care present aggravated early post- traumatic stress reaction which is highly predictive of post-traumatic stress disorder (PTSD) development and severity. The use of ketamine in the acute trauma phase may directly or indirectly interfere with neural processes of memory consolidation of the traumatic event, thus leading to the formation of maladaptive memories, a hallmark symptom of PTSD. We have recently shown that ketamine anesthesia, immediately after a traumatic event, enhances memory consolidation and leads to long-lasting alterations of social behavior in rats. Based on the evidence that ketamine induces a robust central and peripheral adrenergic/noradrenergic potentiation and that activation of this system is essential for the formation of memory for stressful events, we explored the possibility that the strong sympathomimetic action of ketamine might underlie its memory enhancing effects. We found that rats given immediate, but not delayed, post-training ketamine anesthesia (125 mg/kg) presented enhanced 48-h memory retention in an inhibitory avoidance task and that these effects were blocked by adrenal medullectomy, lesions of the locus coeruleus, systemic or intra-basolateral amygdala ß-adrenergic receptor antagonism. Thus, the memory enhancing effects of ketamine anesthesia are time-dependent and mediated by a combined peripheral-central sympathomimetic action. We elucidated a mechanism by which ketamine exacerbates acute post-traumatic reaction, possibly leading to development of PTSD symptomatology later in life. These findings will help guide for a better management of sedation/anesthesia in emergency care to promote the prophylaxis and reduce the risk of developing trauma-related disorders in trauma victims.

Social deprivation substantially changes multi-structural neurotransmitter signature of social interaction: Glutamate concentration in amygdala and VTA as a key factor in social encounter-induced 50-kHz ultrasonic vocalization

Ultrasonic vocalizations are important for coordinating social behavior in rats. Examination of the neurochemical mechanisms that govern social behavior and ultrasonic vocalization emission is crucial for understanding the social impairments that occur in many neuropsychiatric disorders. To elucidate neurochemical changes in the brain structures related to social behavior and their mutual relationships, we conducted three-phase experiment. Neurochemicals were measured in the following behavioral situations: without social encounter, with short social encounter, with long social encounter in isolated and non-isolated rats. The aims of this study were to: (1) extract the most important neurotransmitters and their metabolites that are involved in social encounter-induced emission of 50 kHz calls; (2) to elucidate mutual relationships among the neurochemical changes in the selected, six brain structures, and analyze compound relationships by step analysis; (3) create a model of all-to-all neurotransmitter correlations; (4) find the neurochemical basis of 50-kHz USVs emission during social encounter. Our behavioral and neurochemical analysis indicated that social encounter was a triggering factor of the glutamatergic neurotransmission in the ventral tegmental area (VTA), hippocampus, and amygdala; serotonergic neurotransmission in the NAcc, CPu, and amygdala; the dopaminergic neurotransmission in the caudate putamen (CPu) and hippocampus; GABAergic neurotransmission in the hippocampus and VTA. Social encounter-induced 50-kHz USVs were bound up with changes in glutamate in amygdala and VTA, glycine in the amygdala, VTA, hippocampus, nucleus accumbens and CPu, and dopamine metabolites in VTA and CPu.

Gap junctions and expression of Cx36, Cx43 and Cx45 in the posterodorsal medial amygdala of adult rats.

The posterodorsal medial amygdala (MePD) has an adapted synaptic organization that dynamically modulates reproduction and other social behaviors in rats. Discrete gap junctions between glial cells were previously reported in the MePD neuropil. Connexins (Cx) are components of gap junctions and indicative of cellular electrical coupling. Here, we report the ultrastructural occurrence of gap junctions between neurons in the MePD and demonstrate the expression and immunofluorescent labeling of Cx36, Cx43 and Cx45 in this subcortical area of adult male rats. Few neuronal gap junctions were found in the MePD and, when identified, occurred between dendrites. On the other hand, there is a diffuse presence and distribution of punctate labelling for the tested Cxs. Puncta were visualized isolated or forming clusters in the same focal plane of cell bodies or along the MePD neuropil. The Cx36 puncta were found in neurons, Cx43 in astrocytes and Cx45 in both neurons and astrocytes. Our data indicate the presence of few gap junctions and different Cxs composition in the MePD. Because Cxs can assemble, form hemichannel units and/or serve as transcriptional regulator, it is likely that additional modulation of intercellular communication can occur besides the chemical transmission in the MePD of adult rats.

The development of synaptic transmission is time-locked to early social behaviors in rats

The development of functional synapses is a sequential process preserved across many brain areas. Here, we show that glutamatergic postsynaptic currents anticipated GABAergic currents in Layer II/III of the rat neocortex, in contrast to the pattern described for other brain areas. The frequencies of both glutamatergic and GABAergic currents increased abruptly at the beginning of the second postnatal week, supported by a serotonin upsurge. Integrative behaviors arose on postnatal day (P)9, while most motor and sensory behaviors, which are fundamental for pup survival, were already in place at approximately P7. A reduction in serotonin reuptake accelerated the development of functional synapses and integrative huddling behavior, while sparing motor and sensory function development. A decrease in synaptic transmission in Layer II/III induced by a chemogenetic approach only inhibited huddling. Thus, precise developmental sequences mediate early, socially directed behaviors for which neurotransmission and its modulation in supragranular cortical layers play key roles.

Comparing vasopressin and oxytocin fiber and receptor density patterns in the social behavior neural network: Implications for cross-system signaling.

Vasopressin (AVP) and oxytocin (OXT) regulate social behavior by binding to their canonical receptors, the vasopressin V1a receptor (V1aR) and oxytocin receptor (OTR), respectively. Recent studies suggest that these neuropeptides may also signal via each other's receptors. The extent to which such cross-system signaling occurs likely depends on anatomical overlap between AVP/OXT fibers and V1aR/OTR expression. By comparing AVP/OXT fiber densities with V1aR/OTR binding densities throughout the rat social behavior neural network (SBNN), we propose the potential for cross-system signaling in four regions: the medial amygdala (MeA), bed nucleus of the stria terminalis (BNSTp), medial preoptic area, and periaqueductal grey. We also discuss possible implications of corresponding sex (higher in males versus females) and age (higher in adults versus juveniles) differences in AVP fiber and OTR binding densities in the MeA and BNSTp. Overall, this review reveals the need to unravel the consequences of potential cross-system signaling between AVP and OXT systems in the SBNN for the regulation of social behavior.