Unanticipated stressful and rewarding experiences engage the same prefrontal cortex and ventral tegmental area neuronal populations

© 2020 Del Arco et al. Brain networks that mediate motivated behavior in the context of aversive and rewarding experiences involve the prefrontal cortex (PFC) and ventral tegmental area (VTA). Neurons in both regions are activated by stress and reward, and by learned cues that predict aversive or appetitive outcomes. Recent studies have proposed that separate neuronal populations and circuits in these regions encode learned aversive versus appetitive contexts. But how about the actual experience? Do the same or different PFC and VTA neurons encode unanticipated aversive and appetitive experiences? To address this, we recorded unit activity and local field poten-tials (LFPs) in the dorsomedial PFC (dmPFC) and VTA of male rats as they were exposed, in the same recording session, to reward (sucrose) or stress (tail pinch) spaced 1 h apart. As expected, experience-specific neuronal responses were observed. Approximately 15–25% of single units in each region responded by excitation or inhibition to either stress or reward, and only stress increased LFP theta oscillation power in both regions and coherence between regions. But the largest number of responses (29% dmPFC and 30% VTA units) involved dual-valence neurons that responded to both stress and reward exposure. Moreover, the temporal profile of neuronal population activity in dmPFC and VTA as assessed by principal component analysis (PCA) were similar during both types of experiences. These results reveal that aversive and rewarding experiences engage overlapping neuronal populations in the dmPFC and the VTA. These populations may provide a locus of vulnerability for stress-related disorders, which are often associated with anhedonia

Using Intra-Aortic Balloon Pump for Management of Cardiogenic Shock Following Aluminum Phosphide Poisoning; Report of 3 Cases

Introduction: Aluminium phosphide (Alp) poisoning mortality rate has been reported as high as 70-100%, and refractory hypotension and cardiogenic shock are the two most common presentations leading to death. Due to lack of specific antidote, all treatments are focused on supportive care and recently, intra-aortic balloon pump (IABP) has been suggested to treat cardiogenic shock resulting from toxic myocarditis. In the current paper, we introduce three Alp poisoned patients for whom IABP was applied to manage their refractory shock. Case presentation: Two men and one woman who were admitted to emergency department (ED) of Imam Reza academic Hospital, Mashhad, Iran due to intentional Alp poisoning are reported. The cases visited the ED shortly after ingestion and nearly all of them showed hypotension, tachycardia and metabolic acidosis during early hospitalization. Due to persistent shock state, despite receiving intravenous fluid therapy and vasopressor agents, IABP insertion was performed in these cases. Finally, one of them survived and the other two died. Conclusion: It still cannot be decided whether IABP insertion is effective in cases of Alp poisoning or not. It might be reasonable to try this intervention along with other conservative treatments in patients who survive more than 12 hours and consistently suffer from refractory hypotension

Autism's Impact on Cochlear Implantation Surgery Outcomes in Deaf Children

Introduction:Cochlear implants (CI) provide a hearing sense for severe to profound hearing-impaired patients, both adults and children, and they are a broadly effective and accepted therapeutic method for those patients. Also, Deaf children with comorbidities, including autism spectrum disorders (ASDs), undergo cochlear implantation. ASDs are a group of developing disorders characterized by abnormalities in social interaction and communication with limited repetitive patterns of behavior. This study aimed to assess the effect of Autism on CI surgery outcomes in Deaf Children.Materials and Methods:We followed 12 autistic patients with cochlear implantation and 12 non-autistic cochlear-implanted patients for two years. The Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores were used to assess 6, 12, and 24 months after cochlear implantation surgery. Results: During the 24-month follow-up, the CAP means scores increased in both groups, and SIR and CAP progresses were considerably greater in non-ASD children (P<0.001). However, in ASD children, the progress of CAP and SIR variables were significant, with 99% and 95% confidence, respectively, at 24 months after surgery.Conclusion:Although the CIs could improve hearing performance in autistic patients, speech development after CIs in autistic children could affected by several factors, including the severity of autism, and this can be effective in providing pre-implant counseling to parents. The application of the alternative communication methods could be taken into account as a potential rehab technique

Coordinated Activity of Ventral Tegmental Neurons Adapts to Appetitive and Aversive Learning

Our understanding of how value-related information is encoded in the ventral tegmental area (VTA) is based mainly on the responses of individual putative dopamine neurons. In contrast to cortical areas, the nature of coordinated interactions between groups of VTA neurons during motivated behavior is largely unknown. These interactions can strongly affect information processing, highlighting the importance of investigating network level activity. We recorded the activity of multiple single units and local field potentials (LFP) in the VTA during a task in which rats learned to associate novel stimuli with different outcomes. We found that coordinated activity of VTA units with either putative dopamine or GABA waveforms was influenced differently by rewarding versus aversive outcomes. Specifically, after learning, stimuli paired with a rewarding outcome increased the correlation in activity levels between unit pairs whereas stimuli paired with an aversive outcome decreased the correlation. Paired single unit responses also became more redundant after learning. These response patterns flexibly tracked the reversal of contingencies, suggesting that learning is associated with changing correlations and enhanced functional connectivity between VTA neurons. Analysis of LFP recorded simultaneously with unit activity showed an increase in the power of theta oscillations when stimuli predicted reward but not an aversive outcome. With learning, a higher proportion of putative GABA units were phase locked to the theta oscillations than putative dopamine units. These patterns also adapted when task contingencies were changed. Taken together, these data demonstrate that VTA neurons organize flexibly as functional networks to support appetitive and aversive learning

Advancing drug discovery for schizophrenia

Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, "Advancing Drug Discovery for Schizophrenia" was held March 9-11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia

Following the genes: a framework for animal modeling of psychiatric disorders

The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans

Impact of Metabotropic Glutamate 2/3 Receptor Stimulation On Activated Dopamine Release and Locomotion

Rationale: Activation of metabotropic glutamate (mGlu) 2/3 receptors may provide a novel strategy for treating schizophrenia. This effect is thought to be mediated through dopamine-independent mechanisms because mGlu2/3-receptor agonists have no considerable affinity for dopamine receptors. These agonists, however, reduce amphetamine-induced hyperlocomotion suggesting that they influence dopamine neurotransmission. Objective: We evaluated whether the inhibitory effect of mGlu2/3-receptor activation on amphetamine-induced hyperlocomotion correlates with attenuated dopamine release. We also assessed whether mGlu 2/3 receptor activation has inhibitory effects on activity-dependent vesicular release of dopamine in behaving animals. Methods: Microdialysis was used to measure extracellular levels of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) of freely moving rats. The effect of the mGlu2/3-receptor agonist LY354740 on dopamine release and locomotion elicited by amphetamine, electrical stimulation of the ventral tegmental area, or L-dopa was assessed. Results: We find that the inhibitory effect of mGlu2/3 activation on amphetamine-induced hyperlocomotion correlates with an attenuated increase in dopamine release in the NAc and DStr. However, when dopamine levels were increased by electrical stimulation of dopamine neurons or by administration of the dopamine precursor L-dopa, activation of mGlu2/3 receptors had no effect on dopamine release or on behavior. Conclusions: Activation of mGlu2/3 receptors attenuates amphetamine-induced dopamine release through a mechanism that does not affect activity dependent vesicular release, reuptake or synthesis of dopamine

Methylphenidate has nonlinear dose effects on cued response inhibition in adults but not adolescents

Ongoing development of the dopamine system during adolescence may provide a partial mechanism for behavioral and psychiatric vulnerabilities. Despite early evidence for a hyperactive adolescent dopaminergic system, recent data suggest that adolescent dopamine may be functionally hypoactive compared to in adults. While this distinction has been established in response to dopaminergic drugs and natural rewards, little is known about age-related differences in cognitive efficacy of dopaminergic drugs. Using a recently established Cued Response Inhibition Task, we tested the effects of acute systemic methylphenidate, commonly known as Ritalin, on response inhibition and response initiation in adolescent and adults rats. First, we replicated previous data that adolescents are able to inhibit a response to a cue on par with adults, but are slower to produce a rewarded response after a stop cue. Next, we observed that methylphenidate modulated response inhibition in adult rats, with low dose (0.3 mg/kg) improving inhibition, and high dose (3 mg/kg) impairing performance. This dose-response pattern is commonly observed with psychostimulant cognitive modulation. In adolescents, however, methylphenidate had no effect on response inhibition at any dose. Latency of response initiation after the stop cue was not affected by methylphenidate in either adult or adolescent rats. These data establish that dose-response of a commonly prescribed psychostimulant medication is different in adolescents and adults. They further demonstrate that healthy adolescent response inhibition is not as sensitive to psychostimulants as in adults, supporting the idea that the dopamine system is hypoactive in adolescence. This article is part of a Special Issue entitled SI: Adolescent plasticity