scholarly journals Reduced ribosomal DNA transcription in the prefrontal cortex of suicide victims: consistence of new molecular RT-qPCR findings with previous morphometric data from AgNOR-stained pyramidal neurons

2021 ◽  
Author(s):  
Marta Krzyżanowska ◽  
Krzysztof Rębała ◽  
Johann Steiner ◽  
Michał Kaliszan ◽  
Dorota Pieśniak ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Ribosomal Dna ◽  
Pyramidal Neurons ◽  
Quantitative Polymerase Chain Reaction ◽  
Anterior Cingulate ◽  
Rdna Transcription ◽  
Relative Level ◽  
Prefrontal Cortical ◽  
Dorsolateral Cortex ◽  
Cortical Regions

AbstractPrefrontal cortical regions play a key role in behavioural regulation, which is profoundly disturbed in suicide. The study was carried out on frozen cortical samples from the anterior cingulate cortex (dorsal and ventral parts, ACd and ACv), the orbitofrontal cortex (OFC), and the dorsolateral cortex (DLC) obtained from 20 suicide completers (predominantly violent) with unknown psychiatric diagnosis and 21 non-suicidal controls. The relative level of ribosomal RNA (rRNA) as a marker of the transcriptional activity of ribosomal DNA (rDNA) was evaluated bilaterally in prefrontal regions mentioned above (i.e. in eight regions of interest, ROIs) by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The overall statistical analysis revealed a decrease in rDNA activity in suicide victims versus controls, particularly in male subjects. Further ROI-specific post hoc analyses revealed a significant decrease in this activity in suicides compared to non-suicides in five ROIs. This effect was accentuated in the ACv, where it was observed bilaterally. Our findings suggest that decreased rDNA transcription in the prefrontal cortex plays an important role in suicide pathogenesis and corresponds with our previous morphometric analyses of AgNOR-stained neurons.

scholarly journals The Role of Primate Prefrontal Cortex in Bias and Shift Between Visual Dimensions

2019 ◽  
Vol 30 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Farshad A Mansouri ◽  
Mark J Buckley ◽  
Daniel J Fehring ◽  
Keiji Tanaka
Keyword(s):  
Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Top Down ◽  
Attentional Processes ◽  
Prefrontal Cortical ◽  
Frontopolar Cortex ◽  
Dorsolateral Prefrontal ◽  
Cortical Regions ◽  
Visual Cortical ◽  
Bilateral Lesions

Abstract Imaging and neural activity recording studies have shown activation in the primate prefrontal cortex when shifting attention between visual dimensions is necessary to achieve goals. A fundamental unanswered question is whether representations of these dimensions emerge from top-down attentional processes mediated by prefrontal regions or from bottom-up processes within visual cortical regions. We hypothesized a causative link between prefrontal cortical regions and dimension-based behavior. In large cohorts of humans and macaque monkeys, performing the same attention shifting task, we found that both species successfully shifted between visual dimensions, but both species also showed a significant behavioral advantage/bias to a particular dimension; however, these biases were in opposite directions in humans (bias to color) versus monkeys (bias to shape). Monkeys’ bias remained after selective bilateral lesions within the anterior cingulate cortex (ACC), frontopolar cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), or superior, lateral prefrontal cortex. However, lesions within certain regions (ACC, DLPFC, or OFC) impaired monkeys’ ability to shift between these dimensions. We conclude that goal-directed processing of a particular dimension for the executive control of behavior depends on the integrity of prefrontal cortex; however, representation of competing dimensions and bias toward them does not depend on top-down prefrontal-mediated processes.

scholarly journals Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during instructed threat of shock

2020 ◽  
Author(s):  
Jayne Morriss ◽  
Tiffany Bell ◽  
Nicolò Biagi ◽  
Tom Johnstone ◽  
Carien M. van Reekum
Keyword(s):  
Prefrontal Cortex ◽  
Anxiety Disorder ◽  
Intolerance Of Uncertainty ◽  
Neural Circuitry ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Prefrontal Cortical ◽  
Cortical Regions ◽  
Rostral Prefrontal Cortex ◽  
Threat Of Shock

AbstractHeightened responding to uncertain threat is associated with anxiety disorder pathology. Here, we sought to determine if individual differences in self-reported intolerance of uncertainty (IU) underlie differential recruitment of neural circuitry during instructed threat of shock (n = 42). During the task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings, skin conductance and functional magnetic resonance imaging was acquired. Overall, participants displayed greater amygdala activation to uncertain threat vs. safe cues, in the absence of an effect of IU. However, we found that high was associated with greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat vs safe cues. These findings suggest that, during instructed threat of shock, IU is specifically related, over trait anxiety, to activation in prefrontal cortical regions. Taken together, these findings highlight the potential of self-reported IU in identifying mechanisms that may be related to conscious threat appraisal and anxiety disorder pathology.

scholarly journals Muscarinic Acetylcholine Receptor Localization on Distinct Excitatory and Inhibitory Neurons Within the ACC and LPFC of the Rhesus Monkey

2022 ◽  
Vol 15 ◽  
Author(s):  
Alexandra Tsolias ◽  
Maria Medalla
Keyword(s):  
Prefrontal Cortex ◽  
Muscarinic Receptors ◽  
Calcium Binding ◽  
Pyramidal Neurons ◽  
Muscarinic Acetylcholine Receptor ◽  
Anterior Cingulate ◽  
Inhibitory Neurons ◽  
Receptor Localization ◽  
Cortical Inputs ◽  
Almost All

Acetylcholine (ACh) can act on pre- and post-synaptic muscarinic receptors (mAChR) in the cortex to influence a myriad of cognitive processes. Two functionally-distinct regions of the prefrontal cortex—the lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC)—are differentially innervated by ascending cholinergic pathways yet, the nature and organization of prefrontal-cholinergic circuitry in primates are not well understood. Using multi-channel immunohistochemical labeling and high-resolution microscopy, we found regional and laminar differences in the subcellular localization and the densities of excitatory and inhibitory subpopulations expressing m1 and m2 muscarinic receptors, the two predominant cortical mAChR subtypes, in the supragranular layers of LPFC and ACC in rhesus monkeys (Macaca mulatta). The subset of m1+/m2+ expressing SMI-32+ pyramidal neurons labeled in layer 3 (L3) was denser in LPFC than in ACC, while m1+/m2+ SMI-32+ neurons co-expressing the calcium-binding protein, calbindin (CB) was greater in ACC. Further, we found between-area differences in laminar m1+ dendritic expression, and m2+ presynaptic localization on cortico-cortical (VGLUT1+) and sub-cortical inputs (VGLUT2+), suggesting differential cholinergic modulation of top-down vs. bottom-up inputs in the two areas. While almost all inhibitory interneurons—identified by their expression of parvalbumin (PV+), CB+, and calretinin (CR+)—expressed m1+, the localization of m2+ differed by subtype and area. The ACC exhibited a greater proportion of m2+ inhibitory neurons compared to the LPFC and had a greater density of presynaptic m2+ localized on inhibitory (VGAT+) inputs targeting proximal somatodendritic compartments and axon initial segments of L3 pyramidal neurons. These data suggest a greater capacity for m2+-mediated cholinergic suppression of inhibition in the ACC compared to the LPFC. The anatomical localization of muscarinic receptors on ACC and LPFC micro-circuits shown here contributes to our understanding of diverse cholinergic neuromodulation of functionally-distinct prefrontal areas involved in goal-directed behavior, and how these interactions maybe disrupted in neuropsychiatric and neurological conditions.

scholarly journals Neural mechanisms of self-affirmation’s stress buffering effects

2020 ◽  
Vol 15 (10) ◽  
pp. 1086-1096 ◽  
Author(s):  
Janine M Dutcher ◽  
Naomi I Eisenberger ◽  
Hayoung Woo ◽  
William M P Klein ◽  
Peter R Harris ◽  
...  
Keyword(s):  
Stress Responses ◽  
Neural Mechanisms ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Stress Buffering ◽  
Prefrontal Cortical ◽  
Stress Task ◽  
Within Subjects ◽  
Improved Performance ◽  
Cortical Regions

Abstract Self-affirmation can buffer stress responses across different contexts, yet the neural mechanisms for these effects are unknown. Self-affirmation has been shown to increase activity in reward-related neural regions, including the ventral striatum and ventromedial prefrontal cortex (VMPFC). Given that reward-related prefrontal cortical regions such as the VMPFC are involved in reducing neurobiological and behavioral responses to stress, we hypothesized that self-affirmation would activate VMPFC and also reduce neural responses to stress in key neural threat system regions such as the dorsal anterior cingulate cortex (dACC) and anterior insula (AI). We explored this hypothesis using self-affirmation and evaluative stress tasks following a within-subjects design in the fMRI scanner. Consistent with prior work, self-affirmation blocks led to lower self-reported stress and improved performance. With respect to neural activity, compared to control blocks, self-affirmation blocks led to greater VMPFC activity, and subsequently less left AI (but not dACC) activity during stress task blocks. Functional connectivity analyses revealed greater connectivity between the VMPFC and left and right AI during self-affirmation compared to control. These findings begin to articulate the neural circuits involved in self-affirmation’s effects during exposure to stressors, and more broadly specify neural reward-based responses to stressful situations.

scholarly journals Morphology of Pyramidal Neurons in the Rat Prefrontal Cortex: Lateralized Dendritic Remodeling by Chronic Stress

2007 ◽  
Vol 2007 ◽  
pp. 1-14 ◽  
Author(s):  
Claudia Perez-Cruz ◽  
Jeanine I. H. Müller-Keuker ◽  
Urs Heilbronner ◽  
Eberhard Fuchs ◽  
Gabriele Flügge
Keyword(s):  
Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Right Hemisphere ◽  
Anterior Cingulate ◽  
Chronic Restraint Stress ◽  
Hemispheric Difference ◽  
Infralimbic Cortex ◽  
Dendritic Length ◽  
The Right ◽  
Apical Dendrites

The prefrontal cortex (PFC) plays an important role in the stress response. We filled pyramidal neurons in PFC layer III with neurobiotin and analyzed dendrites in rats submitted to chronic restraint stress and in controls. In the right prelimbic cortex (PL) of controls, apical and distal dendrites were longer than in the left PL. Stress reduced the total length of apical dendrites in right PL and abolished the hemispheric difference. In right infralimbic cortex (IL) of controls, proximal apical dendrites were longer than in left IL, and stress eliminated this hemispheric difference. No hemispheric difference was detected in anterior cingulate cortex (ACx) of controls, but stress reduced apical dendritic length in left ACx. These data demonstrate interhemispheric differences in the morphology of pyramidal neurons in PL and IL of control rats and selective effects of stress on the right hemisphere. In contrast, stress reduced dendritic length in the left ACx.

scholarly journals Intolerance of uncertainty is associated with heightened responding in the prefrontal cortex during cue-signalled uncertainty of threat

2021 ◽  
Author(s):  
Jayne Morriss ◽  
Tiffany Bell ◽  
Nicolò Biagi ◽  
Tom Johnstone ◽  
Carien M. van Reekum
Keyword(s):  
Prefrontal Cortex ◽  
Skin Conductance Response ◽  
Intolerance Of Uncertainty ◽  
Neural Circuitry ◽  
Negative Valence ◽  
Amygdala Activation ◽  
Prefrontal Cortical ◽  
Cortical Regions ◽  
Rostral Prefrontal Cortex ◽  
Threat Of Shock

AbstractHeightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

GABA-ergic Modulation of Prefrontal Spatio-temporal Activation Pattern during Emotional Processing: A Combined fMRI/MEG Study with Placebo and Lorazepam

2002 ◽  
Vol 14 (3) ◽  
pp. 348-370 ◽  
Author(s):  
Georg Northoff ◽  
Thomas Witze ◽  
Andre Richter ◽  
Matthias Gessner ◽  
Florian Schlagenhauf ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Emotional Processing ◽  
Activation Pattern ◽  
Cortical Function ◽  
Gaba A ◽  
Emotional Function ◽  
Prefrontal Cortical ◽  
Cortical Motor ◽  
Spatio Temporal ◽  
Cortical Regions

Various prefrontal cortical regions have been shown to be activated during emotional stimulation, whereas neurochemical mechanisms underlying emotional processing in the prefrontal cortex remain unclear. We therefore investigated the influence of the GABA-A potentiator lorazepam on prefrontal cortical emotional—motor spatio-temporal activation pattern in a combined functional magnetic resonance imaging/magnetoencephalography study. Lorazepam led to the reversal in orbito-frontal activation pattern, a shift of the early magnetic field dipole from the orbito-frontal to medial prefrontal cortex, and alterations in premotor/motor cortical function during negative and positive emotional stimulation. It is concluded that negative emotional processing in the orbito-frontal cortex may be modulated either directly or indirectly by GABA-A receptors. Such a modulation of orbito-frontal cortical emotional function by lorazepam has to be distinguished from its effects on cortical motor function as being independent from the kind of processing either emotional or nonemotional.

scholarly journals Expression of α1-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT2A receptors

2013 ◽  
Vol 16 (5) ◽  
pp. 1139-1151 ◽  
Author(s):  
Noemí Santana ◽  
Guadalupe Mengod ◽  
Francesc Artigas
Keyword(s):  
Prefrontal Cortex ◽  
Adrenergic Receptors ◽  
Antipsychotic Drugs ◽  
Pyramidal Neurons ◽  
Anterior Cingulate ◽  
Lower Percentage ◽  
Neuronal Populations ◽  
Cellular Expression ◽  
Behavioural Interactions

Abstract The prefrontal cortex (PFC) is involved in behavioural control and cognitive processes that are altered in schizophrenia. The brainstem monoaminergic systems control PFC function, yet the cells/networks involved are not fully known. Serotonin (5-HT) and norepinephrine (NE) increase PFC neuronal activity through the activation of α1-adrenergic receptors (α1ARs) and 5-HT2A receptors (5-HT2ARs), respectively. Neurochemical and behavioural interactions between these receptors have been reported. Further, classical and atypical antipsychotic drugs share nmin vitro affinity for α1ARs while having preferential affinity for D2 and 5-HT2ARs, respectively. Using double in situ hybridization we examined the cellular expression of α1ARs in pyramidal (vGluT1-positive) and GABAergic (GAD65/67-positive) neurons in rat PFC and their co-localization with 5-HT2ARs. α1ARs are expressed by a high proportion of pyramidal (59–85%) and GABAergic (52–79%) neurons. The expression in pyramidal neurons exhibited a dorsoventral gradient, with a lower percentage of α1AR-positive neurons in infralimbic cortex compared to anterior cingulate and prelimbic cortex. The expression of α1A, α1B and α1D adrenergic receptors was segregated in different layers and subdivisions. In all them there is a high co-expression with 5-HT2ARs (∼80%). These observations indicate that NE controls the activity of most PFC pyramidal neurons via α1ARs, either directly or indirectly, via GABAergic interneurons. Antipsychotic drugs can thus modulate the activity of PFC via α1AR blockade. The high co-expression with 5-HT2ARs indicates a convergence of excitatory serotonergic and noradrenergic inputs onto the same neuronal populations. Moreover, atypical antipsychotics may exert a more powerful control of PFC function through the simultaneous blockade of α1ARs and 5-HT2ARs.

scholarly journals The Fragile Brain: Stress Vulnerability, Negative Affect and GABAergic Neurocircuits in Psychosis

2019 ◽  
Vol 45 (6) ◽  
pp. 1170-1183 ◽  
Author(s):  
Stephan F Taylor ◽  
Tyler B Grove ◽  
Vicki L Ellingrod ◽  
Ivy F Tso
Keyword(s):  
Prefrontal Cortex ◽  
Negative Affect ◽  
Anterior Cingulate ◽  
Gamma Aminobutyric Acid ◽  
Dorsal Anterior Cingulate Cortex ◽  
Stress Vulnerability ◽  
Neuroimaging Data ◽  
Cortical Regions ◽  
Persons With Schizophrenia ◽  
Gaba Function

Abstract Persons with schizophrenia exhibit sensitivity to stress and negative affect (NA), both strongly correlated with poor functional outcome. This theoretical review suggests that NA reflects a “fragile brain,” ie, vulnerable to stress, including events not experienced as stressful by healthy individuals. Based on postmortem evidence of altered gamma-aminobutyric acid (GABA) function in parvalbumin positive interneurons (PVI), animal models of PVI abnormalities and neuroimaging data with GABAergic challenge, it is suggested that GABAergic disruptions weaken cortical regions, which leads to stress vulnerability and excessive NA. Neurocircuits that respond to stressful and salient environmental stimuli, such as the hypothalamic-pituitary-adrenal axis and the amygdala, are highly dysregulated in schizophrenia, exhibiting hypo- and hyper-activity. PVI abnormalities in lateral prefrontal cortex and hippocampus have been hypothesized to affect cognitive function and positive symptoms, respectively; in the medial frontal cortex (dorsal anterior cingulate cortex and dorsal medial prefrontal cortex), these abnormalities may lead to vulnerability to stress, NA and dysregulation of stress responsive systems. Given that postmortem PVI disruptions have been identified in other conditions, such as bipolar disorder and autism, stress vulnerability may reflect a transdiagnostic dimension of psychopathology.

scholarly journals Dynamic shifts of visual and saccadic signals in prefrontal cortical regions 8Ar and FEF

2019 ◽  
Author(s):  
Sanjeev B. Khanna ◽  
Jonathan A. Scott ◽  
Matthew A. Smith
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Active Vision ◽  
Brain Regions ◽  
Motor Tasks ◽  
Prefrontal Cortical ◽  
Spatial Registration ◽  
Cortical Regions ◽  
Spatial Locations

AbstractActive vision is a fundamental process by which primates gather information about the external world. Multiple brain regions have been studied in the context of simple active vision tasks in which a visual target’s appearance is temporally separated from saccade execution. Most neurons have tight spatial registration between visual and saccadic signals, and in areas such as prefrontal cortex (PFC) some neurons show persistent delay activity that links visual and motor epochs and has been proposed as a basis for spatial working memory. Many PFC neurons also show rich dynamics, which have been attributed to alternative working memory codes and the representation of other task variables. Our study investigated the transition between processing a visual stimulus and generating an eye movement in populations of PFC neurons in macaque monkeys performing a memory guided saccade task. We found that neurons in two subregions of PFC, the frontal eye fields (FEF) and area 8Ar, differed in their dynamics and spatial response profiles. These dynamics could be attributed largely to shifts in the spatial profile of visual and motor responses in individual neurons. This led to visual and motor codes for particular spatial locations that were instantiated by different mixtures of neurons, which could be important in PFC’s flexible role in multiple sensory, cognitive, and motor tasks.New and NoteworthyA central question in neuroscience is how the brain transitions from sensory representations to motor outputs. The prefrontal cortex contains neurons that have long been implicated as important in this transition and in working memory. We found evidence for rich and diverse tuning in these neurons, that was often spatially misaligned between visual and saccadic responses. This feature may play an important role in flexible working memory capabilities.

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