scholarly journals Determinants of functional synaptic connectivity among amygdala-projecting prefrontal cortical neurons

2021 ◽  
Author(s):  
Yoav Printz ◽  
Pritish Patil ◽  
Mathias Mahn ◽  
Asaf Benjamin ◽  
Anna Litvin ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Large Scale ◽  
Basolateral Amygdala ◽  
Local Network ◽  
Synaptic Connectivity ◽  
Synaptic Organization ◽  
Intrinsic Properties ◽  
Subcortical Structures ◽  
Prefrontal Cortical

The medial prefrontal cortex (mPFC) mediates a variety of complex cognitive functions via its vast and diverse connections with cortical and subcortical structures. Understanding the patterns of synaptic connectivity that comprise the mPFC local network is crucial for deciphering how this circuit processes information and relays it to downstream structures. To elucidate the synaptic organization of the mPFC, we developed a high-throughput optogenetic method for mapping large-scale functional synaptic connectivity. We show that mPFC neurons that project to the basolateral amygdala display unique spatial patterns of local-circuit synaptic connectivity within the mPFC, which distinguish them from the general mPFC cell population. Moreover, the intrinsic properties of the postsynaptic mPFC cell and anatomical position of both cells jointly account for ~7.5% of the variation in probability of connection between mPFC neurons, with anatomical distance and laminar position explaining most of this fraction in variation. Our findings demonstrate a functional segregation of mPFC excitatory neuron subnetworks, and reveal the factors determining connectivity in the mPFC.

scholarly journals Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects

2019 ◽  
Vol 45 (4) ◽  
pp. 694-702 ◽  
Author(s):  
Nicholas L. Balderston ◽  
Emily M. Beydler ◽  
Camille Roberts ◽  
Zhi-De Deng ◽  
Thomas Radman ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Transcranial Magnetic Stimulation ◽  
Healthy Subjects ◽  
Magnetic Stimulation ◽  
Dorsolateral Prefrontal Cortex ◽  
Subcortical Structures ◽  
Prefrontal Cortical ◽  
Dorsolateral Prefrontal ◽  
Before And After ◽  
The Right

AbstractMuch of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.

scholarly journals Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex

2021 ◽  
Author(s):  
Lucas R. Trambaiolli ◽  
Xiaolong Peng ◽  
Julia F. Lehman ◽  
Hesheng Liu ◽  
Suzanne N. Haber
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Large Scale ◽  
Cognitive Networks ◽  
Anterior Cingulate ◽  
Salience Network ◽  
Subcortical Structures ◽  
Dorsal Anterior Cingulate Cortex ◽  
Ventrolateral Prefrontal Cortex ◽  
Caudal Area

AbstractThree large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VAN and DAN) and salience (SN) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VAN and DAN, but its role in the SN is controversial. In this study, we used a translational and multimodal approach to demonstrate the existence of a SN node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomic connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SN nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SN node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SN cortical nodes, thus confirming the caudal area 47/12 as the SN node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VAN, DAN, and SN. Thus, the vlPFC is in a position to switch between these three cognitive networks, suggesting a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.

scholarly journals Cell adhesion factors during adolescence support amygdalo-cortical connections and flexible action later in life

2021 ◽  
Author(s):  
Henry W Kietzman ◽  
Lauren P Shapiro ◽  
Jidong Guo ◽  
Gracy Trinoskey-Rice ◽  
Shannon L Gourley
Keyword(s):  
Prefrontal Cortex ◽  
Cell Adhesion ◽  
Basolateral Amygdala ◽  
Cortical Function ◽  
Response Strategies ◽  
Prefrontal Cortical ◽  
Adult Mice ◽  
Neuronal Remodeling ◽  
Layer V ◽  
Adhesion Activity

Adolescent brain development is characterized by dramatic neuronal remodeling in the prefrontal cortex. This plasticity is presumed to act in part to "set the stage" for prefrontal cortical function in adulthood, but causal relationships have largely not been verified. Integrins are cell adhesion factors that provide a link between the extracellular matrix and the intracellular actin cytoskeleton. We find that b1-integrin presence in the prelimbic subregion of the prefrontal cortex (PL) during adolescence, but not adulthood, is necessary for adult mice to select actions based on reward likelihood and value. These behaviors require coordinated limbic-frontal-striatal circuits. We identified projections from the basolateral amygdala (BLA) to PL as being necessary for mice to express learned response strategies. We then visualized adolescent PL neurons receiving input from the BLA and projecting to the dorsomedial striatum (DMS), a primary striatal output by which the PL controls reward-related behavior. These projection-defined neurons had a more "adult-like" morphology relative to a general population of layer V PL neurons. b1-integrin loss caused the overexpression of stubby-type dendritic spines at the expense of more mature spines, a phenotype not observed when b1-integrins were silenced before or after adolescence. Together, these experiments localize b1-integrin-mediated cell adhesion activity within a developing di-synaptic circuit that coordinates flexible action.

scholarly journals No relative expansion of the number of prefrontal neurons in primate and human evolution

2016 ◽  
Vol 113 (34) ◽  
pp. 9617-9622 ◽  
Author(s):  
Mariana Gabi ◽  
Kleber Neves ◽  
Carolinne Masseron ◽  
Pedro F. M. Ribeiro ◽  
Lissa Ventura-Antunes ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
White Matter ◽  
Human Evolution ◽  
Cortical Neurons ◽  
Absolute Number ◽  
Relative Volume ◽  
Primate Species ◽  
Prefrontal Cortical ◽  
Relative Expansion ◽  
Prefrontal Region

Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

scholarly journals Prefrontal GABAergic Interneurons Gate Long-Range Afferents to Regulate Prefrontal Cortex-Associated Complex Behaviors

2021 ◽  
Vol 15 ◽  
Author(s):  
Sha-Sha Yang ◽  
Nancy R. Mack ◽  
Yousheng Shu ◽  
Wen-Jun Gao
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Long Range ◽  
Basolateral Amygdala ◽  
Spatial Working Memory ◽  
Gabaergic Interneurons ◽  
Subcortical Structures ◽  
Precise Control ◽  
Regulatory Effects ◽  
Fear Expression

Prefrontal cortical GABAergic interneurons (INs) and their innervations are essential for the execution of complex behaviors such as working memory, social behavior, and fear expression. These behavior regulations are highly dependent on primary long-range afferents originating from the subcortical structures such as mediodorsal thalamus (MD), ventral hippocampus (vHPC), and basolateral amygdala (BLA). In turn, the regulatory effects of these inputs are mediated by activation of parvalbumin-expressing (PV) and/or somatostatin expressing (SST) INs within the prefrontal cortex (PFC). Here we review how each of these long-range afferents from the MD, vHPC, or BLA recruits a subset of the prefrontal interneuron population to exert precise control of specific PFC-dependent behaviors. Specifically, we first summarize the anatomical connections of different long-range inputs formed on prefrontal GABAergic INs, focusing on PV versus SST cells. Next, we elaborate on the role of prefrontal PV- and SST- INs in regulating MD afferents-mediated cognitive behaviors. We also examine how prefrontal PV- and SST- INs gate vHPC afferents in spatial working memory and fear expression. Finally, we discuss the possibility that prefrontal PV-INs mediate fear conditioning, predominantly driven by the BLA-mPFC pathway. This review will provide a broad view of how multiple long-range inputs converge on prefrontal interneurons to regulate complex behaviors and novel future directions to understand how PFC controls different behaviors.

scholarly journals Common coding of expected value and value uncertainty memories in the prefrontal cortex and basal ganglia output

2021 ◽  
Vol 7 (20) ◽  
pp. eabe0693
Author(s):  
Ali Ghazizadeh ◽  
Okihide Hikosaka
Keyword(s):  
Prefrontal Cortex ◽  
Basal Ganglia ◽  
Cortical Neurons ◽  
Expected Value ◽  
Common Coding ◽  
Repetition Suppression ◽  
Free Viewing ◽  
Gaze Bias ◽  
Single Unit Recordings ◽  
Value Preferences

Recent evidence implicates both basal ganglia and ventrolateral prefrontal cortex (vlPFC) in encoding value memories. However, comparative roles of cortical and basal nodes in value memory are not well understood. Here, single-unit recordings in vlPFC and substantia nigra reticulata (SNr), within macaque monkeys, revealed a larger value signal in SNr that was nevertheless correlated with and had a comparable onset to the vlPFC value signal. The value signal was maintained for many objects (>90) many weeks after reward learning and was resistant to extinction in both regions and to repetition suppression in vlPFC. Both regions showed comparable granularity in encoding expected value and value uncertainty, which was paralleled by enhanced gaze bias during free viewing. The value signal dynamics in SNr could be predicted by combining responses of vlPFC neurons according to their value preferences consistent with a scheme in which cortical neurons reached SNr via direct and indirect pathways.

scholarly journals Multiple Alu exonization in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

2020 ◽  
Author(s):  
Aniket Bhattacharya ◽  
Vineet Jha ◽  
Khushboo Singhal ◽  
Mahar Fatima ◽  
Dayanidhi Singh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cortical Neurons ◽  
Regulatory Networks ◽  
Large Scale ◽  
Neuronal Development ◽  
Random Sets ◽  
Rna Seq ◽  
Orphan Gene ◽  
Mirna Sponge ◽  
Human Neurons

Abstract Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Our study highlights how exonized Alus could nucleate large-scale mRNA-miRNA interactions. Using a functional genomics approach, we characterize a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that has exonization of 23 Alus in its 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9 kb 3’UTR) and widely expressed. Using publically available datasets, we demonstrate its expression in higher primates and presence in single nucleus RNA-seq of 15928 human cortical neurons. miRanda predicts ∼4700 miRNA recognition elements (MREs) for ∼1000 miRNAs, primarily originated within these 3’UTR-Alus. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbors ≥10 MREs for 140 miRNAs and has cytosolic localization. We further tested whether expression of CYP20A1_Alu-LT correlates with mRNAs harboring similar MRE targets. RNA-seq with conjoint miRNA-seq analysis was done in primary human neurons where we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. 380 genes were positively correlated with its expression (significantly downregulated in heat shock and upregulated in Tat) and they harbored MREs for nine expressed miRNAs which were also enriched in CYP20A1_Alu-LT. MREs were significantly enriched in these 380 genes compared to random sets of differentially expressed genes (p = 8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways thus proposing a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.

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.

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