Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability.
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ABSTRACT:
SUBMITTER: Li L
PROVIDER: S-EPMC8213405 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsEpidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety-like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated.MethodsThe effects of EA stimulation on mechanical allodynia and anxiety-like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu ) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety-like behaviors in SNI mice.ResultsElectroacupuncture significantly alleviated both mechanical allodynia and anxiety-like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu -DRN projections attenuated both mechanical allodynia and anxiety-like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu -DRN pathway did not induce mechanical allodynia and anxiety-like behaviors under physiological conditions, but inhibiting this pathway produced anxiety-like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu -DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu -DRN pathway.ConclusionsThe role of rACCGlu -DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu -DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety-like behaviors.
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Project description:The dorsal raphe nucleus (DRN) has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct in later life depression (LLD) compared to a healthy age-matched population. Resting state functional magnetic resonance imaging (rsfMRI) data from 95 participants (33 LLD and 62 healthy) were collected to examine functional connectivity from the DRN to the whole brain in voxel-wise fashion. The posterior cingulate cortex (PCC) bilaterally showed significantly smaller connectivity in the LLD group than the control group. The DRN to PCC connectivity did not show any association with the depressive status. The findings implicate that the LLD involves disruption of serotoninergic input to the PCC, which has been suggested to be a part of the reduced default mode network in depression.
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Project description:Dorsal anterior cingulate cortex (dACC) is an important region in the processing of both cognition and affect. Recently, transcranial brain stimulation has been used to modulate cortical activity, but it is unclear whether this stimulation has a specific effect on dACC. Based on EEG evidence that frontal midline theta activity is generated in dACC, we hypothesized that transcranial alternating current stimulation (tACS) with theta band frequency would modulate neural networks including dACC. In this study, we examined the effects of theta band tACS on functional networks and emotional state. Graph theory analysis for resting-state functional MRI data revealed that theta band tACS decreased functional integration and hub capacity in dACC, and the attenuation of dACC network function was associated with emotional state change. Overall, these results demonstrate that theta band stimulation can modulate dACC.
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Project description:Deficits in social interaction (SI) are a core symptom of autism spectrum disorders (ASDs); however, treatments for social deficits are notably lacking. Elucidating brain circuits and neuromodulatory signaling systems that regulate sociability could facilitate a deeper understanding of ASD pathophysiology and reveal novel treatments for ASDs. Here we found that in vivo optogenetic activation of the basolateral amygdala-nucleus accumbens (BLA-NAc) glutamatergic circuit reduced SI and increased social avoidance in mice. Furthermore, we found that 2-arachidonoylglycerol (2-AG) endocannabinoid signaling reduced BLA-NAc glutamatergic activity and that pharmacological 2-AG augmentation via administration of JZL184, a monoacylglycerol lipase inhibitor, blocked SI deficits associated with in vivo BLA-NAc stimulation. Additionally, optogenetic inhibition of the BLA-NAc circuit markedly increased SI in the Shank3B-/- mouse, an ASD model with substantial SI impairment, without affecting SI in WT mice. Finally, we demonstrated that JZL184 delivered systemically or directly to the NAc also normalized SI deficits in Shank3B-/- mice, while ex vivo JZL184 application corrected aberrant NAc excitatory and inhibitory neurotransmission and reduced BLA-NAc-elicited feed-forward inhibition of NAc neurons in Shank3B-/- mice. These data reveal circuit-level and neuromodulatory mechanisms regulating social function relevant to ASDs and suggest 2-AG augmentation could reduce social deficits via modulation of excitatory and inhibitory neurotransmission in the NAc.
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Project description:Social sensitivity to other individuals in distress is crucial for survival. The anterior cingulate cortex (ACC) is a structure involved in making behavioral choices and is influenced by observed pain or distress. Nevertheless, our understanding of the neural circuitry underlying this sensitivity is incomplete. Here, we reveal unexpected sex-dependent activation of ACC when parental mice respond to distressed pups by returning them to the nest ("pup retrieval"). We observe sex differences in the interactions between excitatory and inhibitory ACC neurons during parental care, and inactivation of ACC excitatory neurons increased pup neglect. Locus coeruleus (LC) releases noradrenaline in ACC during pup retrieval, and inactivation of the LC-ACC pathway disrupts parental care. We conclude that ACC maintains sex-dependent sensitivity to pup distress under LC modulation. We propose that ACC's involvement in parenting presents an opportunity to identify neural circuits that support sensitivity to the emotional distress of others.
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Project description:We aimed to elucidate the dACC laterality in typically developing children and their sex/age-related differences with a sample of 84 right-handed children (6-16 years, 42 boys). We first replicated the previous finding observed in adults that gray matter density asymmetry in the dACC was region-specific: leftward (left > right) in its superior part, rightward (left < right) in its inferior part. Intrinsic connectivity analysis of these regions further revealed region-specific asymmetric connectivity profiles in dACC as well as their sex and age differences. Specifically, the superior dACC connectivity with frontoparietal network and the inferior dACC connectivity with visual network are rightward. The superior dACC connectivity with the default network (lateral temporal cortex) was more involved in the left hemisphere. In contrast, the inferior dACC connectivity with the default network (anterior medial prefrontal cortex) was more lateralized towards the right hemisphere. The superior dACC connectivity with lateral visual cortex was more distinct across two hemispheres in girls than that in boys. This connection in boys changed with age from right-prominent to left-prominent asymmetry whereas girls developed the connection from left-prominent to no asymmetry. These findings not only highlight the complexity and laterality of the dACC but also provided insights into dynamical structure-function relationships during the development.
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Project description:The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making, monitoring for conflict between competing responses and predicting task difficulty. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.
| S-EPMC3416924 | biostudies-literature
Project description:We hypothesized that during binary economic choice, decision makers use the first option they attend as a default to which they compare the second. To test this idea, we recorded activity of neurons in the dorsal anterior cingulate cortex (dACC) of macaques choosing between gambles presented asynchronously. We find that ensemble encoding of the value of the first offer includes both choice-dependent and choice-independent aspects, as if reflecting a partial decision. That is, its responses are neither entirely pre- nor post-decisional. In contrast, coding of the value of the second offer is entirely decision dependent (i.e., post-decisional). This result holds even when offer-value encodings are compared within the same time period. Additionally, we see no evidence for 2 pools of neurons linked to the 2 offers; instead, all comparison appears to occur within a single functionally homogenous pool of task-selective neurons. These observations suggest that economic choices reflect a context-dependent evaluation of attended options. Moreover, they raise the possibility that value representations reflect, to some extent, a tentative commitment to a choice.
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Project description:Previous neuroimaging studies have suggested that the experience of flow aligns with a relative increase in activation of the dorsal raphe nucleus (DRN), and relative activation decreases of the medial prefrontal cortex (MPFC) and of the amygdala (AMY). In the present study, Dynamic Causal Modeling (DCM) was used to explore effective connectivity between those brain regions. To test our hypothesis that the DRN causally down-regulates activity of the MPFC and/or of the AMY, 23 healthy male students solved mental arithmetic tasks of varying difficulty during functional magnetic resonance imaging. A "flow" condition, with task demands automatically balanced with participants' skill level, was compared with conditions of "boredom" and "overload". DCM models were constructed modeling full reciprocal endogenous connections between the DRN, the MPFC, the AMY, and the calcarine. The calcarine was included to allow sensory input to enter the system. Experimental conditions were modeled as exerting modulatory effects on various possible connections between the DRN, the MPFC, and the AMY, but not on self-inhibitory connections, yielding a total of 64 alternative DCM models. Model space was partitioned into eight families based on commonalities in the arrangement of the modulatory effects. Random effects Bayesian Model Selection (BMS) was applied to identify a possible winning family (and model). Although BMS revealed a clear winning family, an outstanding winning model could not be identified. Therefore, Bayesian Model Averaging was performed over models within the winning family to obtain representative DCM parameters for subsequent analyses to test our hypothesis. In line with our expectations, Bayesian averaged parameters revealed stronger down-regulatory influence of the DRN on the MPFC when participants experienced flow relative to control conditions. In addition, these condition-dependent modulatory effects significantly predicted participants' experienced degree of flow. The AMY was down-regulated irrespective of condition. The present results suggest a causal role for the DRN in modulating the MPFC, contributing to the experience of flow.
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Project description:Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.
| S-EPMC10914613 | biostudies-literature