The high incidence of depression in Parkinson's disease (PD) has been well documented in the clinic; however, the underlying molecular mechanisms of these overlapping pathologies remain elusive. ...Using a rodent model of depression, the Wistar-Kyoto (WKY) rat, we previously demonstrated that in the frontal cortex the altered expression and protein interactions of a- and g-synuclein (a-Syn, g-Syn) were associated with dysregulated trafficking of the norepinephrine transporter (NET). Chronic treatment with desipramine (DMI), a NET-selective antidepressant, caused a disappearance of depressive-like behavior that was accompanied by a change in a-Syn and g-Syn expression and their trafficking of NET. Using this same model, we examined the expression of NET, a-Syn and g-Syn in the hippocampus, amygdale, brainstem, and striatum, all regions implicated in the development or maintenance of depression or PD pathology. Following chronic treatment with DMI, we observed a significant decrease in NET in the hippocampus, amygdala, and brainstem; decrease in g-Syn in the hippocampus and amygdala; and, increase in a-Syn in the hippocampus and amygdala. Unexpectedly, we observed a significant decrease in a-Syn expression in the striatum of the WKY following chronic DMI treatment. The altered expression of NET, a-Syn and g-Syn in different brain suggest that DMI's ability to improve depressive-like behavior in a rodent is associated with region-specific changes in the regulation of NET by a- and g-Syn.
An increasing amount of research effort is being directed toward investigating the neural bases of social cognition from a systems neuroscience perspective. Evidence from multiple animal species is ...beginning to provide a mechanistic understanding of the substrates of social behaviors at multiple levels of neurobiology, ranging from those underlying high-level social constructs in humans and their more rudimentary underpinnings in monkeys to circuit-level and cell-type-specific instantiations of social behaviors in rodents. Here we review literature examining the neural mechanisms of social decision-making in humans, non-human primates and rodents, focusing on the amygdala and the medial and orbital prefrontal cortical regions and their functional interactions. We also discuss how the neuropeptide oxytocin impacts these circuits and their downstream effects on social behaviors. Overall, we conclude that regulated interactions of neuronal activity in the prefrontal-amygdala pathways critically contribute to social decision-making in the brains of primates and rodents.
Individuals often eat calorically dense, highly palatable "comfort" foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) ...reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.
There has been a longstanding debate on whether original fear memory is inhibited or erased after extinction. One possibility that reconciles this uncertainty is that the inhibition and erasure ...mechanisms are engaged in different phases (early or late) of extinction. In this study, using single-session extinction training and its repetition (multiple-session extinction training), we investigated the inhibition and erasure mechanisms in the prefrontal cortex and amygdala of rats, where neural circuits underlying extinction reside. The inhibition mechanism was prevalent with single-session extinction training but faded when single-session extinction training was repeated. In contrast, the erasure mechanism became prevalent when single-session extinction training was repeated. Moreover, ablating the intercalated neurons of amygdala, which are responsible for maintaining extinction-induced inhibition, was no longer effective in multiple-session extinction training. We propose that the inhibition mechanism operates primarily in the early phase of extinction training, and the erasure mechanism takes over after that.
Recent longitudinal neuroimaging studies in patients with electroconvulsive therapy (ECT) suggest local effects of electric stimulation (lateralized) occur in tandem with global seizure activity ...(generalized). We used electric field (EF) modeling in 151 ECT treated patients with depression to determine the regional relationships between EF, unbiased longitudinal volume change, and antidepressant response across 85 brain regions. The majority of regional volumes increased significantly, and volumetric changes correlated with regional electric field (t = 3.77, df = 83, r = 0.38, p=0.0003). After controlling for nuisance variables (age, treatment number, and study site), we identified two regions (left amygdala and left hippocampus) with a strong relationship between EF and volume change (FDR corrected p<0.01). However, neither structural volume changes nor electric field was associated with antidepressant response. In summary, we showed that high electrical fields are strongly associated with robust volume changes in a dose-dependent fashion.
The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors. However, the principles by which this deep brain structure ...encodes social information is poorly understood. We used a miniature microscope to image the Ca2+ dynamics of large neural ensembles in awake behaving mice and tracked the responses of MeA neurons over several months. These recordings revealed spatially intermingled subsets of MeA neurons with distinct temporal dynamics. The encoding of social information in the MeA differed between males and females and relied on information from both individual cells and neuronal populations. By performing long-term Ca2+ imaging across different social contexts, we found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. These findings reveal basic principles underlying the brain’s representation of social information and its modulation by intrinsic and extrinsic factors.
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•Ca2+ imaging in freely behaving mice reveals sex-specific differences in the encoding of social stimuli•MeA depiction of social information relies on population and individual neuron responses•Sexual experience triggers lasting and sex-specific changes in MeApd activity•Changes in the MeApd of sexually experienced males involve the neuropeptide oxytocin
Imaging of the neuronal activity during social encounters over the span of several months reveals sex-specific differences in response to social cues, as well as long-lasting changes in social representation following sexual experience.
Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in ...the nose is converted into a segregated map in the olfactory bulb. Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.
Summary Background Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic ...activity predicts risk of subsequent cardiovascular events. Methods Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent18 F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. Findings 293 patients (median age 55 years IQR 45·0–65·5) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity ( r =0·47; p<0·0001), arterial inflammation ( r =0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation ( r =0·70; p=0·0083). Perceived stress was associated with amygdalar activity ( r =0·56; p=0·0485), arterial inflammation ( r =0·59; p=0·0345), and C-reactive protein ( r =0·83; p=0·0210). Interpretation In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. Funding None.
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