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 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 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 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 Asymmetric effective connectivity between primate anterior cingulate and lateral prefrontal cortex revealed by electrical microstimulation

2018 ◽  
Author(s):  
Verónica Nácher ◽  
Seyed Alireza Hassani ◽  
Thilo Womelsdorf
Keyword(s):  
Prefrontal Cortex ◽  
Effective Connectivity ◽  
Anterior Cingulate ◽  
Inhibitory Neurons ◽  
Synaptic Connectivity ◽  
Reverse Direction ◽  
Neural Firing ◽  
Lateral Prefrontal Cortex ◽  
Electrical Microstimulation ◽  
Human Primate

AbstractThe anterior cingulate cortex (ACC) and lateral prefrontal cortex (IPFC) of the non-human primate show neural firing correlations and synchronize at theta and beta frequencies during the monitoring and shifting of attention. These functional interactions might be based on synaptic connectivity that is equally efficacious in both directions, but it might be that there are systematic asymmetries in connectivity consistent with reports of more effective inhibition within the ACC than IPFC, or with a preponderance of ACC projections synapsing onto inhibitory neurons in the IPFC. Here, we tested effective ACC-IPFC connectivity in awake monkeys and report systematic asymmetries in the temporal patterning and latencies of effective connectivity as measured using electrical microstimulation. We found that ACC stimulation triggered evoked fields (EFPs) were more likely to be multiphasic in the IPFC than in the reverse direction, with a large proportion of connections showing 2-4 inflection points resembling resonance in the 20-30 Hz beta frequency range. Stimulation of ACC → IPFC resulted, on average, in shorter-latency EFPs than IPFC → ACC. Overall, latencies and connectivity strength varied more than two-fold depending on the precise anterior-to-posterior location of the connections. These findings reveal systematic asymmetries in effective connectivity between ACC and IPFC in the awake non-human primate and document the spatial and temporal patchiness of effective synaptic connections. We speculate that measuring effective connectivity profiles will be essential for understanding how local synaptic efficacy and synaptic connectivity translates into functional neuronal interactions to support adaptive behaviors.

Correlated Discharges Among Putative Pyramidal Neurons and Interneurons in the Primate Prefrontal Cortex

2002 ◽  
Vol 88 (6) ◽  
pp. 3487-3497 ◽  
Author(s):  
Christos Constantinidis ◽  
Patricia S. Goldman-Rakic
Keyword(s):  
Cerebral Cortex ◽  
Prefrontal Cortex ◽  
Cross Correlation ◽  
Pyramidal Neurons ◽  
Discharge Rate ◽  
Population Coding ◽  
Inhibitory Neurons ◽  
Short Time Scale ◽  
Common Input ◽  
Local Circuits

Neurophysiological recordings have revealed that the discharges of nearby cortical cells are positively correlated in time scales that range from millisecond synchronization of action potentials to much slower firing rate co-variations, evident in rates averaged over hundreds of milliseconds. The presence of correlated firing can offer insights into the patterns of connectivity between neurons; however, few models of population coding have taken account of the neuronal diversity present in cerebral cortex, notably a distinction between inhibitory and excitatory cells. We addressed this question in the monkey dorsolateral prefrontal cortex by recording neuronal activity from multiple micro-electrodes, typically spaced 0.2–0.3 mm apart. Putative excitatory and inhibitory neurons were distinguished based on their action potential waveform and baseline discharge rate. We tested each pair of simultaneously recorded neurons for presence of significant cross-correlation peaks and measured the correlation of their averaged firing rates in successive trials. When observed, cross-correlation peaks were centered at time 0, indicating synchronous firing consistent with two neurons receiving common input. Discharges in pairs of putative inhibitory interneurons were found to be significantly more strongly correlated than in pairs of putative excitatory cells. The degree of correlated firing was also higher for neurons with similar spatial receptive fields and neurons active in the same epochs of the behavioral task. These factors were important in predicting the strength of both short time scale (<5 ms) correlations and of trial-to-trial discharge rate covariations. Correlated firing was only marginally accounted for by motor and behavioral variations between trials. Our findings suggest that nearby inhibitory neurons are more tightly synchronized than excitatory ones and account for much of the correlated discharges commonly observed in undifferentiated cortical networks. In contrast, the discharge of pyramidal neurons, the sole projection cells of the cerebral cortex, appears largely independent, suggesting that correlated firing may be a property confined within local circuits and only to a lesser degree propagated to distant cortical areas and modules.

Age differences in ventromedial prefrontal cortex functional connectivity during socioemotional content processing

2020 ◽  
Vol 48 (7) ◽  
pp. 1-19
Author(s):  
Ryan T. Daley ◽  
Holly J. Bowen ◽  
Eric C. Fields ◽  
Angela Gutchess ◽  
Elizabeth A. Kensinger
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Age Groups ◽  
Emotional Content ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Supramarginal Gyrus ◽  
Age Related ◽  
Content Processing

Self-relevance effects are often confounded by the presence of emotional content, rendering it difficult to determine how brain networks functionally connected to the ventromedial prefrontal cortex (vmPFC) are affected by the independent contributions of self-relevance and emotion. This difficulty is complicated by age-related changes in functional connectivity between the vmPFC and other default mode network regions, and regions typically associated with externally oriented networks. We asked groups of younger and older adults to imagine placing emotional and neutral objects in their home or a stranger's home. An age-invariant vmPFC cluster showed increased activation for self-relevant and emotional content processing. Functional connectivity analyses revealed age × self-relevance interactions in vmPFC connectivity with the anterior cingulate cortex. There were also age × emotion interactions in vmPFC functional connectivity with the anterior insula, orbitofrontal gyrus, inferior frontal gyrus, and supramarginal gyrus. Interactions occurred in regions with the greatest differences between the age groups, as revealed by conjunction analyses. Implications of the findings are discussed.

scholarly journals Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anterior Cingulate Cortex ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Pyramidal Neurons ◽  
Treatment Options ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Cell Types ◽  
Anterior Cingulate

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

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