Transcriptional Profiling of Amygdala Neurons Implicates PKCδ in Primate Anxious Temperament

Kovner, Rothem; Kalin, Ned H.

doi:10.1177/2470547021989329

Cited by 4 publications

(3 citation statements)

References 6 publications

(12 reference statements)

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“…Also, we can see elevated expression of Protein Kinase C delta ( Prkcd ) in loser species ( Figure 5 , n26, n27) met with attenuation of dopamine-mediated cAMP signaling cascade [ 13 ]. It was mentioned manifesting a fear-related syndrome in anxious/depressive species since 2001 and later [ 19 , 20 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…While Prkcd exemplifies a mitophagy performed by microglia/immune-competent cells (Munson et al, 2021, 2022) [ 23 , 24 ], it confirms playing a distinct role in the brain, being a striatum/amygdale-specific marker in a range of previous studies on MDD [ 19 , 20 ]. It is characteristic of multiple psychiatric statuses, including Early-Life Anxious Temperament [ 21 , 22 ] and depression/suicide behavior [ 27 ]. It is also observed expressing in specific Prkcd -positive GABAergic neurons within the central amygdala, and is shown to modulate/be modulated, in particular, by the Tissue plasminogen activator gene ( tpA ; Plat ; [ 28 ]) affecting behavioral pattern.…”

Section: Resultsmentioning

confidence: 99%

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Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model

Babenko,

Redina,

Smagin

et al. 2024

IJMS

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The analysis of RNA-Sec data from murine bulk tissue samples taken from five brain regions associated with behavior and stress response was conducted. The focus was on the most contrasting brain region-specific genes (BRSG) sets in terms of their expression rates. These BRSGs are identified as genes with a distinct outlying (high) expression rate in a specific region compared to others used in the study. The analysis suggested that BRSG sets form non-randomly connected compact gene networks, which correspond to the major neuron-mediated functional processes or pathways in each brain region. The number of BRSGs and the connection rate were found to depend on the heterogeneity and coordinated firing rate of neuron types in each brain region. The most connected pathways, along with the highest BRSG number, were observed in the Striatum, referred to as Medium Spiny Neurons (MSNs), which make up 95% of neurons and exhibit synchronous firing upon dopamine influx. However, the Ventral Tegmental Area/Medial Raphe Nucleus (VTA/MRN) regions, although primarily composed of monoaminergic neurons, do not fire synchronously, leading to a smaller BRSG number. The Hippocampus (HPC) region, on the other hand, displays significant neuronal heterogeneity, with glutamatergic neurons being the most numerous and synchronized. Interestingly, the two monoaminergic regions involved in the study displayed a common BRSG subnetwork architecture, emphasizing their proximity in terms of axonal throughput specifics and high-energy metabolism rates. This finding suggests the concerted evolution of monoaminergic neurons, leading to unique adaptations at the genic repertoire scale. With BRSG sets, we were able to highlight the contrasting features of the three groups: control, depressive, and aggressive mice in the animal chronic stress model. Specifically, we observed a decrease in serotonergic turnover in both the depressed and aggressive groups, while dopaminergic emission was high in both groups. There was also a notable absence of dopaminoceptive receptors on the postsynaptic membranes in the striatum in the depressed group. Additionally, we confirmed that neurogenesis BRSGs are specific to HPC, with the aggressive group showing attenuated neurogenesis rates compared to the control/depressive groups. We also confirmed that immune-competent cells like microglia and astrocytes play a crucial role in depressed phenotypes, including mitophagy-related gene Prkcd. Based on this analysis, we propose the use of BRSG sets as a suitable framework for evaluating case–control group-wise assessments of specific brain region gene pathway responses.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model

Babenko,

Redina,

Smagin

et al. 2024

IJMS

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“…Investigations into the neural substrates of anxiety disorders and BI in humans 10,[41][42][43][44][45][46] , as well as inhibited temperament and BI in NHPs 35,38,[47][48][49][50][51][52] , have implicated a distributed network of brain regions. Notably, this network includes the central extended amygdala (EAc): a neuroanatomical concept that encompasses the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST).…”

Section: Introductionmentioning

confidence: 99%

Rhesus Infant Nervous Temperament Predicts Peri-Adolescent Central Amygdala Metabolism & Behavioral Inhibition Measured by a Machine-Learning Approach

Holley

Campos

Zhang

et al. 2022

Preprint

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Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc), a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders, and how this relationship is mediated by alterations in the EAc, could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.

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Anxiety and ultrastructural consequences of chronic mild stress in rats

Zhvania

Japaridze

Tizabi

et al. 2022

Neuroscience Letters

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Transcriptional Profiling of Amygdala Neurons Implicates PKCδ in Primate Anxious Temperament

Cited by 4 publications

References 6 publications

Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model

Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model

Rhesus Infant Nervous Temperament Predicts Peri-Adolescent Central Amygdala Metabolism & Behavioral Inhibition Measured by a Machine-Learning Approach

Anxiety and ultrastructural consequences of chronic mild stress in rats

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