Simulating the head of a TrueBeam linear particle accelerator and calculating the photoneutron spectrum on the central axis of a 10-MV photon using particle and heavy-ion transport system code.

Photon energy is higher than the (γ,n) threshold, allowing it to interact with the nuclei of materials with high z properties and liberate fast neutrons. This represents a potentially harmful source of radiation for humans and the environment. This study validated the Monte Carlo simulation, using the particle and heavy-ion transport code system (PHITS) on a TrueBeam 10-MV linear particle accelerator's head shielding model and then used this PHITS code to simulate a photo-neutron spectrum for the transport of the beam. The results showed that, when comparing the simulated to measured PDD and crosslines, 100% of the γ-indexes were <1 (γ3%/3mm) for both simulations, for both phase-space data source and a mono energy source. Neutron spectra were recorded in all parts of the TrueBeam's head, as well as photon neutron spectra at three points on the beamline.

Developing simulation-based learning application for radiation therapy students at pre-clinical stage.

INTRODUCTION: Simulation-based education has been particularly valuable as a preclinical training method that adequately prepares students for clinical practice, including simulation in educational programs enhances the quality of learning outcomes. However, relevant previous research has exhibited several crucial limitations, with most of them having focused solely on the setup procedures. This study aimed to outline the development of an educational application in radiationtherapy and emphasizes the essential factors that radiation therapist technologists(RTTs) must consider in the treatment room from the perspective of experienced RTTs. METHOD: We connected the virtual pendants to the linear accelerator components using C# programming and Unity. Customized scripts were assigned to specific linear accelerator (LINAC) functions, and the patient and RTT avatars were developed. We also included audio feedback for the realistic gantry movement sounds. RESULT: This study outlines various aspects of radiotherapy procedures duringtreatment, such as the simulation of patient positioning, treatment fields, and pendantfunctions, aimed toward enabling the effective use of virtual reality technology inradiation therapy. DISCUSSION: This study explores the potential of an avatar-based app for radiotherapy education, providing foundational data for future trials. CONCLUSION: Simulation learning is the most advantageous pre-clinical instrument for equipping students with the skills necessary for clinical practice. This study's resultsare expected to facilitate radiotherapy students' adoption of clinical replacement applications and improve collaborative partnerships and knowledge sharing. Notably, this application complements traditional learning methods, further enhancing the overall educational experience.

Adolescent social isolation disrupts developmental tuning of neuropeptide circuits in the hypothalamus to amygdala regulating social and defensive behavior.

Engaging in positive social (i.e., prosocial) interactions during adolescence acts to modulate neural circuits that determine adult adaptive behavior. While accumulating evidence indicates that a strong craving for prosocial behavior contributes to sustaining neural development, the consequences of social deprivation during adolescence on social neural circuits, including those involving oxytocin (OXT) and vasopressin (AVP), are poorly characterized. We evaluated adaptive behaviors in socially isolated mice, including anxiety-like, social, and defensive behaviors, along with OXT and AVP neural profiles in relevant brain regions. Social isolation from postnatal day (P-)22 to P-48 induced enhanced defensive and exploratory behaviors, in nonsocial and social contexts. Unlike OXT neurons, AVP+ cell density in the paraventricular nucleus of the hypothalamus increases with age in males. Social isolation also modulated gene expression in the medial amygdala (MeA), including the upregulation of OXT receptors in males and the downregulation of AVP1a receptors in both sexes. Socially isolated mice showed an enhanced defensive, anogenital approach toward a novel adult female during direct social interactions. Subsequent c-Fos mapping revealed diminished neural activity in restricted brain areas, including the MeA, lateral septum, and posterior intralaminar nucleus of the thalamus, in socially isolated mice. These data indicate that neural signals arising from daily social interactions invoke region-specific modification of neuropeptide expression that coordinates with altered defensiveness and neural responsivities, including OXT- and AVP-projecting regions. The present findings indicate an involvement of OXT and AVP circuits in adolescent neural and behavioral plasticity that is tuned by daily social interaction.

Directional vector visualization of scattered rays in mobile c-arm fluoroscopy.

Previous radiation protection-measure studies for medical staff who perform X-ray fluoroscopy have employed simulations to investigate the use of protective plates and their shielding effectiveness. Incorporating directional information enables users to gain a clearer understanding of how to position protective plates effectively. Therefore, in this study, we propose the visualization of the directional vectors of scattered rays. X-ray fluoroscopy was performed; the particle and heavy-ion transport code system was used in Monte Carlo simulations to reproduce the behavior of scattered rays in an X-ray room by reproducing a C-arm X-ray fluoroscopy system. Using the calculated results of the scattered-ray behavior, the vectors of photons scattered from the phantom were visualized in three dimensions. A model of the physician was placed on the directional vectors and dose distribution maps to confirm the direction of the scattered rays toward the physician when the protective plate was in place. Simulation accuracy was confirmed by measuring the ambient dose equivalent and comparing the measured and calculated values (agreed within 10%). The directional vectors of the scattered rays radiated outward from the phantom, confirming a large amount of backscatter radiation. The use of a protective plate between the patient and the physician's head part increased the shielding effect, thereby enhancing radiation protection for the physicians compared to cases without the protective plate. The use of directional vectors and the surrounding dose-equivalent distribution of this method can elucidate the appropriate use of radiation protection plates.

A novel approach to predict acute radiation dermatitis in patients with head and neck cancer using a model based on Bayesian probability.

PURPOSE: In this study, we aimed to establish a method for predicting the probability of each acute radiation dermatitis (ARD) grade during the head and neck Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning phase based on Bayesian probability. METHODS: The skin dose volume >50 Gy (V50), calculated using the treatment planning system, was used as a factor related to skin toxicity. The empirical distribution of each ARD grade relative to V50 was obtained from the ARD grades of 119 patients (55, 50, and 14 patients with G1, G2, and G3, respectively) determined by head and neck cancer specialists. Using Bayes' theorem, the Bayesian probabilities of G1, G2, and G3 for each value of V50 were calculated with an empirical distribution. Conversely, V50 was obtained based on the Bayesian probabilities of G1, G2, and G3. RESULTS: The empirical distribution for each graded patient group demonstrated a normal distribution. The method predicted ARD grades with 92.4 % accuracy and provided a V50 value for each grade. For example, using the graph, we could predict that V50 should be ≤24.5 cm3 to achieve G1 with 70 % probability. CONCLUSIONS: The Bayesian probability-based ARD prediction method could predict the ARD grade at the treatment planning stage using limited patient diagnostic data that demonstrated a normal distribution. If the probability of an ARD grade is high, skin care can be initiated in advance. Furthermore, the V50 value during treatment planning can provide radiation oncologists with data for strategies to reduce ARD.

Revisiting sociability: Factors facilitating approach and avoidance during the three-chamber test.

The three-chamber test, the so-called sociability test, has been widely used to assess social deficits based on impaired socially oriented investigations in rodent models. An innate motivation for investigating conspecifics is theoretically a prerequisite for gaining sociability scores in this paradigm. However, several relevant factors mediating investigatory motives, such as familiarity, attractiveness, and aggression, may affect sociability scores, which must be verified to obtain an adequate evaluation of the psychiatric phenotypes exhibited by disease-relevant rodent models. We assessed the social and non-social factors that mediate proximity preference by the three-chamber test with standard C57BL/6 J (B6) mice and low sociability BTBR+ltpr3tf/J (BTBR) mice. Strains of the opponents had no effect. Sexual cues (i.e., opposite sex) increased proximity preference in both strains of mice; in contrast, novel objects induced an approach in B6 mice but avoidance in BTBR mice. Single-housing before testing, stimulated social motive, affected BTBR mice but not B6 mice. BTBR females showed increased proximity preference across the sessions, and BTBR males showed increased preference toward a male B6 stimulus, but not a male BTBR stimulus. The male preference was restored when the male BTBR stimulus was anesthetized. In addition, self-grooming was facilitated by social and non-social novelty cues in both strains. B6 mice predominantly exhibited an investigatory approach toward social or non-social stimuli, whereas BTBR mice recognized social cues but tended to show avoidance. The three-chamber test could evaluate approach-avoidance strategies in target mouse strains that comprise innate social distance between mice.

Serotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation.

Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.

Serotonergic circuit dysregulation underlying autism-related phenotypes in BTBR mouse model of autism.

The inbred mouse strain, BTBR T+Itpr3tf/J (BTBR), possesses neuronal and circuit abnormalities that underlie atypical behavioral profiles resembling the major symptoms of human autism spectrum disorder (ASD). Forebrain serotonin (5-HT) transmission has been implicated in ASD-related behavioral alterations. In this study, we assessed 5-HT signals and the functional responsiveness in BTBR mice compared to standard C57BL/6J (B6) control mice to elucidate how 5-HT alterations contribute to behavioral abnormalities in BTBR mice. A lower number of 5-HT neurons in the median raphe, but not in the dorsal raphe, was observed in male and female BTBR mice. Acute systemic injection of buspirone, a 5-HT1A receptor agonist, induced c-Fos in several brain regions in both B6 and BTBR mice; however, blunted c-Fos induction in BTBR mice was documented in the cingulate cortex, basolateral amygdala (BLA), and ventral hippocampus (Hipp). Decreased c-Fos responses in these regions are associated with a lack of buspirone effects on anxiety-like behavior in BTBR mice. Analysis of mRNA expression following acute buspirone injection indicated that 5HTR1a gene downregulation (or upregulation) occurred in the BLA and Hipp of B6 mice, respectively, but not BTBR mice. The mRNA expression of factors associated with neurogenesis or the pro-inflammatory state was not consistently altered by acute buspirone injection. Therefore, 5-HT responsivity via 5-HT1A receptors in the BLA and Hipp are linked to anxiety-like behavior, in which circuits are disrupted in BTBR mice. Other distinct 5-HT circuits from the BLA and Hipp that regulate social behavior are restricted but preserved in BTBR mice.

Dose estimation for cone-beam computed tomography in image-guided radiation therapy for pelvic cancer using adult mesh-type reference computational phantoms.

The use of cone-beam computed tomography (CBCT) is expanding owing to its installation in linear accelerators for radiation therapy, and the imaging dose induced by this system has become the center of attention. Here, the dose to patients caused by the CBCT imager was investigated. Organ doses and effective doses for male and female mesh-type reference computational phantoms (MRCPs) and pelvis CBCT mode, routinely used for pelvic irradiation, were estimated using the Particle and Heavy Ion Transport Code System. The simulation results were confirmed based on the point-dose measurements. The estimated organ doses for male MRCPs with/without raised arms and for female MRCPs with/without raised arms were 0.00286-35.6 mGy, 0.00286-35.1 mGy, 0.00933-39.5 mGy, and 0.00931-39.0 mGy, respectively. The anticipated effective doses for male MRCPs with/without raised arms and female MRCPs with/without raised arms irradiated by pelvis CBCT mode were 4.25 mSv, 4.16 mSv, 7.66 mSv, and 7.48 mSv, respectively. The results of this study will be useful for patients who undergo image-guided radiotherapy with CBCT. However, because this study only covered one type of cancer with one type of imager, and image quality was not considered, more studies should be conducted to estimate the radiation dose from imaging devices in radiation therapy.

Oxytocin neurons in the paraventricular nucleus of the hypothalamus circuit-dependently regulates social behavior, which malfunctions in BTBR mouse model of autism.

Oxytocin (OXT) a neuropeptide synthesized in the hypothalamic nuclei has a variety of function including socio-emotional processes in mammals. While the neural circuits and signaling pathways in central OXT converge in the paraventricular nucleus of the hypothalamus (PVN), we illuminate specific function of discrete PVN OXT circuits, which connect to the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BnST) in mouse models. The OXTPVN→BnST projections are innervated from entire portions of the PVN, while those OXTPVN→MeA projections are asymmetrically innervated from the posterior portion of the PVN. Compared with OXT neurons in B6 wild type mice, BTBR mice that are recognized as a behavior-based autism model exhibited defect in the OXTPVN→BnST projection. We demonstrate that chemogenetic activation of OXTPVN→MeA circuit enhances anxiety-like behavior and facilitates social approach behavior, while activation of OXTPVN→BnST circuit suppresses anxiety-like behavior along with inhibiting social approach. This chemogenetic manipulation on the OXTPVN→BnST circuit proves ineffective in BTBR mice. Accordingly, chemogenetic activation of OXTPVN neurons that stimulate both OXT circuits induces OXT receptor expressions in both MeA and BnST as with those by social encounter in B6 mice. The induction of OXT receptor genes in the BnST was not observed in BTBR mice. These data support the hypothesis that OXT circuits serve as a regulator for OXT signaling in PVN to control socio-emotional approach/avoidance behavior, and a defect of OXTPVN→BnST circuit contributes to autism-like social phenotypes in BTBR mice.

Faded neural projection from the posterior bed nucleus of the stria terminalis to the lateral habenula contributes to social signaling deficit in male BTBR mice as a mouse model of autism.

BTBR T+ Itpr3tf/J (BTBR) mice display several behavioral characteristics, including social deficits resembling the core symptoms of human autism. Atypical social behaviors include sequential processes of assembled cognitive-behavior components, such as recognition, investigatory assessment, and signaling response. This study aimed to elucidate the neural circuits responsible for the regulation of the social signaling response, as shown by scent marking behavior in male mice. We first assessed the recognition and investigatory patterns of male BTBR mice compared to those of C57BL/6 J (B6) mice. Next, we examined their scent-marking behavior as innate social signaling responses adjusted to a confronted feature of social stimuli and situations, along with the expression of c-Fos as a marker of neuronal activity in selected brain areas involved in the regulation of social behavior. The function of the targeted brain area was confirmed by chemogenetic manipulation. We also examined the social peptides, oxytocin and vasopressin neurons of the major brain regions that are associated with the regulation of social behavior. Our data indicate that male BTBR mice are less responsive to the presentation of social stimuli and the expression of social signaling responses, which is paralleled by blunted c-Fos responsivity and vasopressin neurons morphological changes in selected brain areas, including the posterior bed nucleus of the stria terminalis (pBnST) and lateral habenula (LHb) in BTBR mice. Further investigation of LHb function revealed that chemogenetic inhibition and activation of LHb activity can induce a change in scent marking responses in both B6 and BTBR mice. Our elucidation of the downstream LHb circuits controlling scent marking behavior indicates intact function in BTBR mice. The altered morphological characteristics of oxytocin neurons in the paraventricular nucleus of the hypothalamus and vasopressin-positive neurons and axonal projections in the pBnST and LHb appear to underlie the dysfunction of scent marking responses in BTBR mice. (300/300 words).

Exocrine scent marking: Coordinative role of arginine vasopressin in the systemic regulation of social signaling behaviors.

Arginine vasopressin (AVP) is a neurohypophysial hormone that coordinatively regulates central socio-emotional behavior and peripheral control of antidiuretic fluid homeostasis. Most mammals, including rodents, utilize exocrine or urine-contained scent marking as a social signaling tool that facilitates social adaptation. The exocrine scent marking behavior is postulated to fine-tune sensory and cognitive abilities to recognize key social features via exocrine/urinary olfactory cues and subsequently control exocrine deposition or urinary marking through the mediation of osmotic fluid balance. AVP is implicated as a major player in controlling both recognition and signaling responses. This review provides constructive hypotheses on the coordinative processes of the AVP neurohypophysial circuits in the systemic regulations of fluid control and social-communicative behavior, via the expression of exocrine scent marking, and further emphasizes a potential role of AVP in a common mechanism underlying social communication in rodents.

Contrasting central and systemic effects of arginine-vasopressin on urinary marking behavior as a social signal in male mice.

Arginine-vasopressin (AVP) is a neurohypophyseal peptide that plays a critical role in the regulation of social behavior in mammals. Neuronal AVP regulates male-specific social signaling processes, such as exocrine urinary scent deposition and marking behavior in mice. In the periphery, AVP is transported to the portal bloodstream and acts as an antidiuretic hormone. These AVP dynamics imply that the central role of AVP in the stimulation of urinary marking is dissociated with the peripheral role of AVP in the retention of osmotic conditions. Using male BALB/c mice as subjects, peripheral injection of AVP decreased urinary marking and urination. In contrast, a central infusion of AVP facilitated urinary marking with no effect on urination, while an antagonist of the AVP 1a receptor inhibited marking. Centrally AVP-injected mice also exhibited typical behaviors, such as hiccough/sneeze-like reactions and flash scratching, particularly when confronted with a stimulus mouse through a wire mesh screen. Significant expression of these typical reactions in these mice resulted in the disruption of marking deposition. Further analysis of AVP synthesis illustrated that AVP levels increased in the midbrain but not in the circulation immediately after the test, particularly when confronted with a stimulus mouse. The central AVP regulates urinary marking and other typical behaviors in a dose- and situation-dependent manner. The sequential process implies that centrally synthesized AVP may be secreted into the circulation following immediate neuronal processes, and then peripheral AVP acts as an antidiuretic hormone on urinary marking behavior.

Implication of the social function of excessive self-grooming behavior in BTBR T+ltpr3tf/J mice as an idiopathic model of autism.

Autism spectrum disorder (ASD) is defined by two core behavioral characteristics, namely, restricted repetitive behaviors and impaired social-communicative functioning. BTBR T+ltpr3tf/J (BTBR) mice provide a valuable animal model for ASD to elucidate the underlying mechanisms of these two behavioral characteristics of ASD. This study examined the social function of excessive grooming behavior in BTBR mice as a phenotype of restricted repetitive behaviors. Compared to the control C57BL/6 J (B6) strain, BTBR mice showed increased self-grooming when placed alone in a test apparatus, and this behavior was even more evident when confronted with a stimulus mouse (either B6 or BTBR) in a three-chamber test apparatus. While B6 mice tended to groom their face/snout region on the empty side of the chamber, BTBR mice showed excessive grooming with frequent transitions among grooming body regions on the side of the chamber containing a social stimulus. Acute systemic injection of buspirone,a serotonin 1A receptor agonist, as an anxiolytic, facilitated approach behavior toward social stimuli in the three-chamber setting in both B6 and BTBR mice. However, this treatment did not affect grooming behavior in B6 mice and significantly enhanced self-grooming in BTBR mice. These behaviors in BTBR mice suggest a potential signaling function of grooming in response to social stimuli, in which bodywide grooming of BTBR mice expressed in the proximity of social opponents may stimulate the release of olfactory (possibly dismissive) signals. Consequently, the putative neural mechanisms underlying excessive grooming may differ from those regulating social approaches that are associated with anxiolytic mechanisms.

Chemogenetics drives paradigm change in the investigation of behavioral circuits and neural mechanisms underlying drug action.

Recent developments in chemogenetic approaches to the investigation of brain function have ushered in a paradigm change in the strategy for drug and behavior research and clinical drug-based medications. As the nature of the drug action is based on humoral regulation, it is a challenge to identify the neuronal mechanisms responsible for the expression of certain targeted behavior induced by drug application. The development of chemogenetic approaches has allowed researchers to control neural activities in targeted neurons through a toolbox, including engineered G protein-coupled receptors or ligand-gated ion channels together with exogenously inert synthetic ligands. This review provides a brief overview of the chemogenetics toolbox with an emphasis on the DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technique used in rodent models, which is applicable to the investigation of how specific neural circuits regulate behavioral processes. The use of chemogenetics has had a significant impact on basic neuroscience for a better understanding of the relationships between brain activity and the expression of behaviors with cell- and circuit-specific orders. Furthermore, chemogenetics is potentially a useful tool to deconstruct the neuropathological mechanisms of mental diseases and its regulation by drug, and provide us with transformative therapeutics with medication. We also review recent findings in the use of chemogenetic techniques to uncover functional circuit connections of serotonergic neurons in rodent models.

Wireless Optogenetic Modulation of Cortical Neurons Enabled by Radioluminescent Nanoparticles.

While offering high-precision control of neural circuits, optogenetics is hampered by the necessity to implant fiber-optic waveguides in order to deliver photons to genetically engineered light-gated neurons in the brain. Unlike laser light, X-rays freely pass biological barriers. Here we show that radioluminescent Gd2(WO4)3:Eu nanoparticles, which absorb external X-rays energy and then downconvert it into optical photons with wavelengths of ∼610 nm, can be used for the transcranial stimulation of cortical neurons expressing red-shifted, ∼590-630 nm, channelrhodopsin ReaChR, thereby promoting optogenetic neural control to the practical implementation of minimally invasive wireless deep brain stimulation.

Dynamic regulation of oxytocin neuronal circuits in the sequential processes of prosocial behavior in rodent models.

The expression of positive social (i.e., prosocial) behavior is governed by a multitude of sensory and cognitive abilities to identify and recognize key features of potential social partners, elucidate social and individual status, and maintain appropriate behaviors. Oxytocin (OT) is a neuropeptide that has been implicated as a major player in regulating prosocial behavior, and much of its role in social situations has been uncovered. As social behavior inherently comprises sequential processes related to multimodal assessments of interactive features, a comprehensive approach to understanding the functions of OT in these prosocial behavior sequences is required. Here, the author discusses recent evidence illustrating the functioning of OT neural circuits in the processing of multimodal components of social behavior, including the detection/recognition of social cues via the olfactory bulb through olfactory cortices, evaluation of social features via the circuits of the paraventricular nucleus of the hypothalamus to the medial amygdala, and maintenance of prosocial behaviors via the circuits of the ventral tegmental area to the nucleus accumbens. A review of rodent studies with an emphasis on mice and rats is also provided to investigate the effects of OT in interaction with other neurotransmitters, such as serotonin and dopamine, to characterize the neuromodulatory mechanisms that mediate the sequences of prosocial engagements. The review further highlights OT function as a temporal dynamic of specific neural circuits.

From Multisensory Assessment to Functional Interpretation of Social Behavioral Phenotype in Transgenic Mouse Models for Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a common heterogeneous disorder, defined solely by the core behavioral characteristics, including impaired social interaction and restricted and repeated behavior. Although an increasing number of studies have been performed extensively, the neurobiological mechanisms underlying the core symptoms of ASD remain largely unknown. Transgenic mouse models provide a useful tool for evaluating genetic and neuronal mechanisms underlying ASD pathology, which are prerequisites for validating behavioral phenotypes that mimic the core symptoms of human ASD. The purpose of this review is to propose a better strategy for analyzing and interpreting social investigatory behaviors in transgenic mouse models of ASD. Mice are nocturnal, and employ multimodal processing mechanisms for social communicative behaviors, including those that involve olfactory and tactile senses. Most behavioral paradigms that have been developed for measuring a particular ASD-like behavior in mouse models, such as social recognition, preference, and discrimination tests, are based on the evaluation of distance-based investigatory behavior in response to social stimuli. This investigatory behavior in mice is regulated by multimodal processing involving with two different motives: first, an olfactory-based novelty assessment, and second, tactile-based social contact, in a temporally sequential manner. Accurate interpretation of investigatory behavior exhibited by test mice can be achieved by functional analysis of these multimodal, sequential behaviors, which will lead to a better understanding of the specific features of social deficits associated with ASD in transgenic mouse models, at high temporal and spatial resolutions.

Restraint stress activates defensive behaviors in male rats depending on age and housing condition.

Restraint is a widely used experimental stress manipulation in animal models. It is still unclear, however, whether restraint is associated with physical fatigue leading to overall behavioral inhibition, or if it induces activation of defensive behaviors and strategies to protect against subsequent challenges. The aim of this study was to systematically investigate restraint effects in rats based on housing condition (isolation- vs. pair-housed) and age at the time of testing, both of which are relevant to the expression of defensive strategies. Restraint induced behavioral inhibition in male rats younger than postnatal day 65 in an open-field paradigm, while it activated defensive behaviors in adult rats, depending on their housing condition; thereby pair-housed adult rats exhibited a heightened stretch-attend postures (SAPs) and it was suppressed by restraint, while isolation-housed adult rats displayed lower SAPs but it was enhanced by restraint. Restraint also enhanced pain tolerance, but not pain sensitivity, across all ages, regardless of housing conditions. These results suggest that restraint stress activates defensive systems of male rats, including sensory defenses and exploratory strategies in a novel environment, and these expression patterns vary with age from overall inhibition to changes in defensive behavior strategies. Understanding differential changes in these models could lead to greater consistency and better standardization of rodent models commonly used to assess the impact of stress on anxiety and defensive behaviors.

Somatosensorimotor and Odor Modification, Along with Serotonergic Processes Underlying the Social Deficits in BTBR T+ Itpr3tf/J and BALB/cJ Mouse Models of Autism.

Autism is a complex spectrum of disorders characterized by core behavioral deficits in social communicative behavior, which are also required for comprehensive analysis of preclinical mouse models. As animal models of the core behavioral deficits in autism, two inbred mouse strains, BTBR T+ Itpr3tf/J (BTBR) and BALB/cJ (BALB), were compared with the standard social strain, C57BL/6J (B6), regarding a variety of behavioral factors underlying social communicative interactions, including olfactory and tactile sensory processes, social recognition abilities and behavioral expression strategies. Although both female BTBR and BALB mice can express social recognition and approach behavior depending on the stimuli they encounter, the available sensory modalities, along with modulation of the serotonergic system, differ between the two strains. BALB mice have deficits in using volatile olfactory cues and tactile information in a social context; they fail to exhibit a social approach to volatile cues and seek nonvolatile cues by exhibiting substantial sniff/contact behavior when allowed direct contact with social opponents. Systemic injection of the serotonin (5-HT1A) agonist buspirone has little effect on these social deficits, suggesting a congenitally degraded serotonergic system in BALB mice. In contrast, BTBR mice exhibit impaired body coordination and social motivation-modified olfactory signals, which are relevant to a reduced social approach. A systemic injection of the 5-HT1A agonist restored these social deficits in BTBR mice, indicating that a downregulated serotonergic system is involved in the social deficits exhibited by BTBR mice.