150 research outputs found
Strain-dependent differences in corticolimbic processing of aversive or rewarding stimuli
Aberrations in the elaboration of both aversive and rewarding stimuli characterize
several psychopathologies including anxiety, depression and addiction. Several studies
suggest that different neurotrasmitters, within the corticolimbic system, are critically
involved in the processing of positive and negative stimuli. Individual differences in
this system, depending on genotype, have been shown to act as a liability factor for
different psychopathologies. Inbred mouse strains are commonly used in preclinical
studies of normal and pathological behaviors. In particular, C57BL/6J (C57) and DBA/2J
(DBA) strains have permitted to disclose the impact of different genetic backgrounds
over the corticolimbic system functions. Here, we summarize the main findings
collected over the years in our laboratory, showing how the genetic background
plays a critical role in modulating amminergic and GABAergic neurotransmission in
prefrontal-accumbal-amygdala system response to different rewarding and aversive
experiences, as well as to stress response. Finally, we propose a top-down model for the
response to rewarding and aversive stimuli in which amminergic transmission in prefrontal
cortex (PFC) controls accumbal and amygdala neurotransmitter response
Strain-dependent variations in stress coping behavior are mediated by a 5-HT/GABA interaction within the prefrontal corticolimbic system
Background: Serotonin and γ- Aminobutyric acid (GABA) transmission is crucial in coping strategies. Methods: Here, using mice from 2 inbred strains widely exploited in behavioral neurochemistry, we investigated whether serotonin transmission in medial prefrontal cortex and GABA in basolateral amygdala determine strain-dependent liability to stress response and differences in coping. Results: C57BL/6J mice displayed greater immobility in the forced swimming test, higher serotonin outflow in medial prefrontal cortex, higher GABA outflow in basolateral amygdala induced by stress, and higher serotonin 1A receptor levels in medial prefrontal cortex accompanied by lower GABAb receptor levels in basolateral amygdala than DBA/2J mice. In assessing whether serotonin in medial prefrontal cortex determines GABA functioning in response to stress and passive coping behavior in C57BL/6J and DBA/2J mice, we observed that selective prefrontal serotonin depletion in C57BL/6J and DBA/2J reduced stress-induced GABA outflow in basolateral amygdala and immobility in the forced swimming test. Conclusions: These results show that strain-dependent prefrontal corticolimbic serotonin/GABA regulation determines the strain differences in stress-coping behavior in the forced swimming test and point to a role of a specific neuronal system in genetic susceptibility to stress that opens up new prospects for innovative therapies for stress disorders
Cerebellar BDNF promotes exploration and seeking for novelty
Approach system considered a motivational system that activates reward-seeking behavior is associated with exploration/impulsivity, whereas avoidance system considered an attentional system that promotes inhibition of appetitive responses is associated with active overt withdrawal. Approach and avoidance dispositions are modulated by distinct neurochemical profiles and synaptic patterns. However, the precise working of neurons and trafficking of molecules in the brain activity predisposing to approach and avoidance are yet unclear
Effects of lack of microRNA-34 on the neural circuitry underlying the stress response and anxiety
Stress-related psychiatric disorders, including anxiety, are complex diseases that have genetic, and
environmental causes. Stressful experiences increase the release of prefrontal amygdala neurotransmitters,
a response that is relevant to cognitive, emotional, and behavioral coping. Moreover, exposure to
stress elicits anxiety-like behavior and dendritic remodeling in the amygdala. Members of the miR-34
family have been suggested to regulate synaptic plasticity and neurotransmission processes, which
mediate stress-related disorders. Using mice that harbored targeted deletions of all 3 members of the
miR-34-family (miR-34-TKO), we evaluated acute stress-induced basolateral amygdala (BLA)-GABAergic
and medial prefrontal cortex (mpFC) aminergic outflow by intracerebral in vivo microdialysis. Moreover,
we also examined fear conditioning/extinction, stress-induced anxiety, and dendritic remodeling in the
BLA of stress-exposed TKO mice.
We found that TKO mice showed resilience to stress-induced anxiety and facilitation in fear extinction.
Accordingly, no significant increase was evident in aminergic prefrontal or amygdala GABA release, and
no significant acute stress-induced amygdalar dendritic remodeling was observed in TKO mice. Differential
GRM7, 5-HT2C, and CRFR1 mRNA expressionwas noted in the mpFC and BLA between TKO andWT
mice. Our data demonstrate that the miR-34 has a critical function in regulating the behavioral and
neurochemical response to acute stress and in inducing stress-related amygdala neuroplasticity
Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature
Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug
use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic
events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely
limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social
experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaineseeking
after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that
this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain
microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal
abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a
possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent
individuals
Evaluation of Italian Simplified Matrix Test for Speech-Recognition Measurements in Noise
This study aimed at the evaluation of a simplified Italian matrix test (SiIMax) for speech-recognition measurements in noise for adults and children. Speech-recognition measurements with adults and children were conducted to examine the training effect and to establish reference speech-recognition thresholds of 50% (SRT50) and 80% (SRT80) correct responses. Test-list equivalency was evaluated only with adults. Twenty adults and 96 children—aged between 5 and 10 years—participated. Evaluation measurements with the adults confirmed the equivalence of the test lists, with a mean SRT50 of −8.0 dB and a standard deviation of 0.2 dB across the test lists. The test-specific slope (the average of the list-specific slopes) was 11.3%/dB, with a standard deviation of 0.6%/dB. For both adults and children, only one test list of 14 phrases needs to be presented to account for the training effect. For the adults, adaptive measurements of the SRT50 and SRT80 showed mean values of −7.0 ± 0.6 and −4.5 ± 1.1 dB, respectively. For children, a slight influence of age on the SRT was observed. The mean SRT50s were −5.6 ± 1.2, −5.8 ± 1.2 and −6.6 ± 1.3 dB for the children aged 5–6, 7–8 and 9–10 years, respectively. The corresponding SRT80s were −1.5 ± 2.7, −3.0 ± 1.7 and −3.7 ± 1.4 dB. High test–retest reliabilities of 1.0 and 1.1 dB for the SRT80 were obtained for the adults and children, respectively. This makes the test suitable for accurate and reliable speech-recognition measurements
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