scholarly journals Sex-dependent effects of traumatic stress on social behavior and neuronal activation in the prefrontal cortex and amygdala

2021 ◽  
Author(s):  
Mariia Dorofeikova ◽  
Chandrashekhar D Borkar ◽  
Katherine Weissmuller ◽  
Lydia Smith-Osborne ◽  
Samhita Basavanhalli ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Interaction ◽  
Social Behavior ◽  
Acute Stress ◽  
Negative Impact ◽  
Early Gene ◽  
Central Nucleus ◽  
Dependent Manner ◽  
Neuronal Activation ◽  
Footshock Stress

Social behavior is complex and fundamental, and deficits in social behavior are common pathological features for a variety of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Acute stress has a negative impact on social behavior, and these effects may vary based on sex. The aim of this study was to explore the effect of footshock stress on the sociability of male and female C57Bl/6J mice. Animals were divided into two main groups of footshock exposure or context exposure control. Each group had mice that were treated with either the benzodiazepine alprazolam, or vehicle. Neuronal activation during social interaction was assessed using immunohistochemistry against the immediate early gene product cFos. Footshock stress induced a significantly increased latency to approach a social interaction counterpart in both sexes. Stress-induced increases in defensive tail-rattling behavior elicited during the sociability test were sex-dependent and alleviated by alprazolam. Alprazolam also lowered social exploration and neuronal activation in the infralimbic medial prefrontal cortex. Social interaction induced sex-dependent differences in cFos activation in the lateral subdivision of the central nucleus of the amygdala and ventromedial intercalated cell clusters. Overall, our results suggest that acute footshock stress induces alterations in sociability and patterns of cFos activation in a sex-dependent manner.

scholarly journals Early maturational emergence of adult-like emotional reactivity and anxiety after brief exposure to an obesogenic diet

2020 ◽  
Author(s):  
Julio D. Vega-Torres ◽  
Matine Azadian ◽  
Raul Rios-Orsini ◽  
Arsenio L. Reyes-Rivera ◽  
Perla Ontiveros-Angel ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Emotional Reactivity ◽  
Fear Extinction ◽  
Mrna Levels ◽  
Neuronal Activation ◽  
Short Term ◽  
Footshock Stress ◽  
Obesogenic Diet ◽  
Adolescent Rats ◽  
Fear Potentiated Startle

ABSTRACTBackgroundEmerging evidence demonstrates that diet-induced obesity disrupts corticolimbic circuits underlying emotional regulation. Studies directed at understanding how obesity alters brain and behavior are easily confounded by a myriad of complications related to obesity. This study investigated the early neurobiological stress response triggered by an obesogenic diet. Furthermore, this study directly determined the combined impact of a short-term obesogenic diet and adolescence on critical behavioral and molecular substrates implicated in emotion regulation and stress.MethodsAdolescent (postnatal day 31) or adult (postnatal day 81) Lewis rats were fed for one week with an experimental Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). We used the acoustic fear-potentiated startle (FPS) paradigm to determine the effects of the WD on cued fear conditioning and fear extinction. We used c-Fos mapping to determine the functional influence of the diet and stress on corticolimbic circuits.ResultsWe report that one-week WD consumption was sufficient to induce fear extinction deficits in adolescent rats, but not in adult rats. We identify fear-induced alterations in corticolimbic neuronal activation and demonstrate increased prefrontal cortex CRHR1 mRNA levels in the rats that consumed the WD.ConclusionsOur findings demonstrate that short-term consumption of an obesogenic diet during adolescence heightens behavioral and molecular vulnerabilities associated with risk for anxiety and stress-related disorders. Given that fear extinction promotes resilience, and that fear extinction principles are the foundation of psychological treatments for PTSD, understanding how obesogenic environments interact with the adolescent period to affect the acquisition and expression of fear extinction memories is of tremendous clinical relevance.HIGHLIGHTSShort-term WD consumption during adolescence impairs cued fear extinction memory retention in a fear-potentiated startle paradigm.Short-term WD consumption during adolescence attenuates neuronal activation to electric footshock stress in the basomedial nuclei of the amygdala.Short-term WD consumption increases CRHR1 mRNA levels in the medial prefrontal cortex.Adult LEW rats exhibit increased basal HPA axis tone and heightened emotional reactivity to footshock stress relative to adolescent rats.

scholarly journals Angiotensin II AT1Receptors Are Involved in Neuronal Activation Induced by Amphetamine in a Two-Injection Protocol

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Constanza Paz ◽  
Natalia Andrea Marchese ◽  
Liliana M. Cancela ◽  
Claudia Bregonzio
Keyword(s):  
Prefrontal Cortex ◽  
Early Gene ◽  
Receptor Blocker ◽  
Prelimbic Cortex ◽  
Ang Ii ◽  
Neuronal Activation ◽  
Single Exposure ◽  
Injection Protocol ◽  
Fos Expression ◽  
Amphetamine Sensitization

It was already found that Ang II AT1receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine, and such changes are related to the development of behavioral and neurochemical sensitization. The induction of the immediately early gene c-fos has been used to define brain activated areas by amphetamine. Our aim was to evaluate the participation of AT1receptors in the neuronal activation induced by amphetamine sensitization. The study examined the c-fos expression in mesocorticolimbic areas induced by amphetamine challenge (0.5 mg/kg i.p) in animals pretreated with candesartan, a selective AT1receptor blocker (3 mg/kg p.o × 5 days), and amphetamine (5 mg/kg i.p) 3 weeks before the challenge. Increased c-fos immunoreactivity was found in response to the amphetamine challenge in the dorsomedial caudate-putamen and nucleus accumbens, and both responses were blunted by the AT1receptor blocker pretreatment. In the infralimbic prefrontal cortex, increased c-fos immunoreactivity was found in response to amphetamine and saline challenge, and both were prevented by the AT1receptor blocker. No differences were found neither in ventral tegmental area nor prelimbic cortex between groups. Our results indicate an important role for brain Ang II in the behavioral and neuronal sensitization induced by amphetamine.

scholarly journals Increased expression of schizophrenia-associated gene C4 leads to hypoconnectivity of prefrontal cortex and reduced social interaction

2019 ◽  
Author(s):  
Ashley L. Comer ◽  
Tushare Jinadasa ◽  
Lisa N. Kretsge ◽  
Thanh P.H. Nguyen ◽  
Jungjoon Lee ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Interaction ◽  
Social Behavior ◽  
Social Interactions ◽  
Confocal Imaging ◽  
Immune Gene ◽  
Causative Role ◽  
Severe Mental Disorder ◽  
Brain Disorder ◽  
Spine Development

ABSTRACTSchizophrenia is a severe mental disorder with an unclear pathophysiology. Increased expression of the immune gene C4 has been linked to a greater risk of developing schizophrenia; however, it is unknown whether C4 plays a causative role in this brain disorder. Using confocal imaging and whole-cell electrophysiology, we demonstrate that overexpression of C4 in mouse prefrontal cortex neurons leads to perturbations in dendritic spine development and hypoconnectivity, which mirror neuropathologies found in schizophrenia. We find evidence that microglia-neuron interactions and microglia-mediated synaptic engulfment are enhanced with increased expression of C4. We also show that C4-dependent circuit dysfunction in the frontal cortex leads to decreased social interactions in juvenile mice. These results demonstrate that increased expression of the schizophrenia-associated gene C4 causes aberrant circuit wiring in the developing prefrontal cortex and leads to deficits in early social behavior, suggesting that altered C4 expression contributes directly to schizophrenia pathogenesis.

scholarly journals Prefrontal-amygdalar oscillations related to social interaction behavior in mice

2021 ◽  
Author(s):  
Takuya Sasaki ◽  
Nahoko Kuga ◽  
Reimi Abe ◽  
Kotomi Takano ◽  
Yuji Ikegaya
Keyword(s):  
Prefrontal Cortex ◽  
Social Interaction ◽  
Social Behavior ◽  
Basolateral Amygdala ◽  
Neuronal Population ◽  
Social Avoidance ◽  
Wild Type ◽  
Interaction Behavior ◽  
Neurophysiological Mechanisms ◽  
Medial Pfc

The medial prefrontal cortex and amygdala are involved in the regulation of social behavior and associated with psychiatric diseases but their detailed neurophysiological mechanisms at a network level remain unclear. We recorded local field potentials (LFPs) from the dorsal medial PFC (dmPFC) and basolateral amygdala (BLA) while mice engaged on social behavior. We found that in wild-type mice, both the dmPFC and BLA increased 4–7 Hz oscillation power and decreased 30–60 Hz power when they needed to attend to another target mouse. In mouse models with reduced social interactions, dmPFC 4–7 Hz power further increased especially when they exhibited social avoidance behavior. In contrast, dmPFC and BLA decreased 4–7 Hz power when wild-type mice socially approached a target mouse. Frequency-specific optogenetic manipulations of replicating social approach-related LFP patterns restored social interaction behavior in socially deficient mice. These results demonstrate a neurophysiological substrate of the prefrontal cortex and amygdala related to social behavior and provide a unified pathophysiological understanding of neuronal population dynamics underlying social behavioral deficits.

A new model as an early life manipulation: Fake mother

2017 ◽  
Vol 41 (S1) ◽  
pp. S346-S346
Author(s):  
M. Kucukkarapinar ◽  
A. Dönmez ◽  
S. Candansayar ◽  
A. Bozkurt ◽  
E. Akçay
Keyword(s):  
Prefrontal Cortex ◽  
Social Interaction ◽  
Social Behavior ◽  
Aggressive Behavior ◽  
Early Life ◽  
Social Interaction Test ◽  
Protein Levels ◽  
Maternal Odor ◽  
Interaction Test

IntroductionEarly life stressful events cause long-term neural changes that are associated with psychiatric disorders.ObjectiveEarly life manipulations focus on commonly the impact of remaining separate from the mother in a specific period of time. The maternal odor is required for pups to approach the mother for nursing. What happens when there is a mother that smell like a real mother but does not take care her own pups?AimTo investigate the fake mother effects on adult rat's behavioral changes, NMDR2B protein level changes in prefrontal cortex and hippocampus.MethodsWistar rats were used. Fake mother (n:13), early handling (n:12), maternal separation (n:14) and control (n:12) were the study groups. A fake mother is an object that smells like a real dam. When the real mother is separated from own pups fake mother stays with the pups for an hour. Manipulations were made during the postnatal first 14 days. Behavioral tests (social interaction test, elevated plus maze, novel object recognition test) were made between postnatal 62 and 78 days. NMDAR2B protein levels in prefrontal cortex and hippocampus were evaluated by using ELISA at postnatal 78 days.ResultsIn social interaction test, fake mother group exhibited less social behavior and more aggressive behavior than the other groups. Their long-term memory functions were the lowest. NMDAR2B protein levels in the hippocampus increased in rats that exposed to early stressful life events.ConclusionThese results support that being raised by fake mother increases aggressive behavior and decrease social behavior in adulthood.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals APOE4 genotype exacerbates the depression-like behavior of mice during aging through ATP decline

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenting Fang ◽  
Naian Xiao ◽  
Guirong Zeng ◽  
Daode Bi ◽  
Xiaoman Dai ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Acute Stress ◽  
Temporal Cortex ◽  
Underlying Mechanism ◽  
Population Based ◽  
Dependent Manner ◽  
Late Life Depression ◽  
Positron Emission ◽  
Cultured Astrocytes ◽  
Mitochondrial Functions

AbstractPopulation-based studies reveal that apolipoprotein E (APOE) ε4 gene allele is closely associated with late-life depression (LLD). However, its exact role and underlying mechanism remain obscure. The current study found that aged apoE4-targeted replacement (TR) mice displayed obvious depression-like behavior when compared with age-matched apoE3-TR mice. Furthermore, apoE4 increased stress-induced depression-like behaviors, accompanied by declines in the hippocampal 5-HT (1A) radioligand [18F] MPPF uptake evidenced by positron emission tomography (PET). In [18F]-fluorodeoxyglucose PET ([18F]-FDG PET) analyses, the FDG uptake in the prefrontal cortex, temporal cortex and hippocampus of apoE4-TR mice significantly declined when compared with that of apoE3-TR mice after acute stress. Further biochemical analysis revealed that ATP levels in the prefrontal cortex of apoE4-TR mice decreased during aging or stress process and ATP supplementation effectively rescued the depression-like behaviors of elderly apoE4-TR mice. In primary cultured astrocytes from the cortex of apoE-TR mice, apoE4, when compared with apoE3, obviously decreased the mitochondrial membrane potential, mitochondrial respiration, and glycolysis in a culture time-dependent manner. Our findings highlight that apoE4 is a potential risk factor of depression in elderly population by impairing the glucose metabolism, reducing ATP level, and damaging mitochondrial functions in astrocytes, which indicates that in clinical settings ATP supplementation may be effective for elderly depression patients with apoE4 carrier.

Nerve Injury Alters Restraint-induced Activation of the Basolateral Amygdala in Male Rats

2021 ◽  
Author(s):  
James Kang ◽  
David Mor ◽  
Kevin A Keay
Keyword(s):  
Prefrontal Cortex ◽  
Nerve Injury ◽  
Restraint Stress ◽  
Basolateral Amygdala ◽  
Acute Stress ◽  
Male Rats ◽  
Neuronal Activation ◽  
Acute Restraint Stress ◽  
The Right ◽  
Psychological Stressor

Abstract The amygdala is critical for the production of appropriate responses towards emotional or stressful stimuli. It has a characteristic neuronal activation pattern to acute stressors. Chronic pain and acute stress have each been shown to independently modulate the activity of the amygdala. Few studies have investigated the effect of pain or injury, on amygdala activation to acute stress. This study investigated the effects of a neuropathic injury on the activation response of the amygdala to an acute restraint stress. Chronic constriction injury of the right sciatic nerve (CCI) was used to create neuropathic injury and a single brief 15-minute acute restraint was used as an emotional/psychological stressor. All rats received cholera toxin B (CTB) retrograde tracer injections into the medial prefrontal cortex (mPFC) to assess if the amygdala to mPFC pathway was specifically regulated by the combination of neuropathic injury and acute stress. To assess differential patterns of activity in amygdala subregions, cFos expression was used as a marker for “acute”, restraint triggered neuronal activation, and FosB/DFosB expression was used to reveal prolonged neuronal activation / sensitisation triggered by CCI. Restraint resulted in a characteristic increase in cFos expression in the medial amygdala, which was not altered by CCI. Rats with a CCI showed increased cFos expression in the basolateral amygdala (BLA), in response to an acute restraint stress, but not in neurons projecting to the prefrontal cortex. Further, CCI rats showed an increase in FosB/ΔFosB expression which was exclusive to the BLA. This increase likely reflects sensitisation of the BLA as a consequence of nerve injury which may contribute to heightened sensitivity of BLA neurons to acute emotional/ psychological stressors.

scholarly journals Social Interactions of DAT-HET Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

2021 ◽  
Author(s):  
Anna Brancato ◽  
Sara Lo Russo ◽  
Anna Sara Liberati ◽  
Cristiana Carbone ◽  
Silvia Zelli ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Interaction ◽  
Social Behavior ◽  
Social Preference ◽  
Male Rats ◽  
Preclinical Model ◽  
Genetic Trait ◽  
Knock Out ◽  
Noradrenaline Transporter ◽  
Comparable Control

Social interaction is essential for life and is impaired in many psychiatric disorders like schizophrenia, au-tism, depression and major anxiety disorder. Monoamine transmission plays a key role in social behavior and both genetic and epigenetic modifications of dopamine and noradrenaline neurotransmission-related genes can affect the levels of social interaction. Since heterozygous individuals for a specific genetic trait possess only one mutant allele of that trait, in order to better evaluate the role of the interaction between genetics and epigenetics in unmasking latent genetically-determined predispositions, our interest has focused on studying the interplay between genetics and epigenetics influences on social behavior in male rats obtained by two different breeding schemes: a first group by breeding of knock-out (KO) male rats with wild-type (WT) female dams (homogeneous heterozygous offspring, termed MAT-HET), and a second group of heterozygous DAT male offspring by breeding of KO male and DAT-heterozygous female subjects (to obtain comparable control pups, termed MIX-HET). Their social behavior was then assessed by partner preference, social preference and elicited preference tests. In the first test MIX-HET and MAT-HET male mice had choice between two WT females one in estrous and the other not in estrous. In the second test they met either a MIX-HET or a WT male rodent. Also, the expression of the noradrenaline transporter (NET) was assessed in the prefrontal cortex, hippocampus and hypothalamus of MAT, MIX and WTs by immunofluorescence in order to estimate its involvement in the expression of social behavior. Our results show that MIX-HET focal rodents tend to have an asocial behavior when in contact with a female in estrous, and their behavior is similar to when the stimulus is a MIX-HET male. MAT-HET male rodents, instead, tend to be very attracted by the female in estrous, but they ignore the MIX-HET stimulus. MIX-HET progeny showed a lower expression of noradrenaline transporter in both hypothalamus and hippocampus with respect to MAT-HET rats, whereas MAT-HET rats displayed increased noradrenaline transporter immunofluorescence in the hypothalamus and in the hippocampus with respect to WT rats, while no difference was observed in the prefrontal cortex. Therefore we can hypothesize that the differences observed between the two heterozygous groups may be attributable to an epigenetic factor: the different maternal care received. These data can open new perspectives towards increased the preclinical knowledge about autism and bipolar disorder.

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