scholarly journals Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

2020 ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler
Keyword(s):  
Partial Agonist ◽  
Insular Cortex ◽  
Initial Step ◽  
Gabaergic Neurons ◽  
Binding Potential ◽  
Projection Neurons ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Serotonin 2A ◽  
Insular Populations

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed six neural populations, including two defined by their fast amino acid transmitter (excitatory or inhibitory), and four defined by their projections to different downstream targets. First, we found that more than 70% of glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, 5-HT1A is highly expressed (~80%) in the insular populations projecting to two sub-nuclei of the amygdala (central and basolateral), as well as in the populations projecting to the rostral and caudal sections of the lateral hypothalamus (LH). Similarly, 70% of insular glutamatergic neurons and only 20% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in most of insula-amygdala and insula-LH projection neurons (>60%). These observations suggest that a majority of glutamatergic neurons can respond to 5-HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

scholarly journals Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

2020 ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler
Keyword(s):  
Partial Agonist ◽  
Insular Cortex ◽  
Initial Step ◽  
Gabaergic Neurons ◽  
Binding Potential ◽  
Projection Neurons ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Serotonin 2A

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

scholarly journals Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

2020 ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler
Keyword(s):  
Partial Agonist ◽  
Insular Cortex ◽  
Initial Step ◽  
Gabaergic Neurons ◽  
Binding Potential ◽  
Projection Neurons ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Serotonin 2A

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75-80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73-82%). These observations suggest that most glutamatergic neurons can respond to 5‑HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

scholarly journals Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Anes Ju ◽  
Beatriz Fernandez-Arroyo ◽  
Yifan Wu ◽  
Débora Jacky ◽  
Anna Beyeler
Keyword(s):  
Partial Agonist ◽  
Insular Cortex ◽  
Initial Step ◽  
Gabaergic Neurons ◽  
Projection Neurons ◽  
Target Region ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Serotonin 2A

Abstract The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5-HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potentials within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5-HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5-HT1A or 5-HT2A. We analyzed seven neural populations, including three defined by a molecular marker (putative glutamate, GABA or parvalbumin), and four defined by their projections to different downstream targets. First, we found that more than 70% of putative glutamatergic neurons, and only 30% of GABAergic neurons express the 5-HT1A. Second, within insular projection neurons, 5-HT1A is highly expressed (75–80%) in the populations targeting one sub-nuclei of the amygdala (central or basolateral), or targeting the rostral or caudal sections of the lateral hypothalamus (LH). Similarly, 70% of putative glutamatergic neurons and only 30% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in a majority of insula-amygdala and insula-LH projection neurons (73–82%). These observations suggest that most glutamatergic neurons can respond to 5-HT through 5-HT1A or 5-HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.

scholarly journals Linking emotional valence and anxiety in a mouse insula-amygdala circuit

2021 ◽  
Author(s):  
Céline Nicolas ◽  
Anes Ju ◽  
Yifan Wu ◽  
Hazim Eldirdiri ◽  
Sebastien Delcasso ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Ex Vivo ◽  
Insular Cortex ◽  
Emotional Valence ◽  
Projection Neurons ◽  
Negative Valence ◽  
Glutamatergic Neurons ◽  
Related Information ◽  
Starting Point ◽  
Positive And Negative Valence

Abstract The response of the insular cortex (IC) and amygdala to stimuli of positive and negative valence were found to be altered in patients with anxiety disorders. However, the coding properties of neurons controlling anxiety and valence remain unknown. Combining photometry recordings and chemogenetics in mice, we uncover the anxiogenic control of projection neurons in the anterior IC (aIC), independently of their projection target. Using viral tracing and ex vivo electrophysiology, we characterize the monosynaptic aIC to the basolateral amygdala (BLA) connection, and employed projection-specific optogenetics, to reveal anxiogenic properties of aIC-BLA neurons in anxiety-related behaviors. Finally, using photometry recordings, we identified that aIC-BLA neurons are active in anxiogenic spaces, and in response to aversive stimuli. Together, these findings show that negative valence, as well as anxiety-related information and behaviors, are encoded by aICBLA glutamatergic neurons, providing a starting point to understand how alterations of this pathway contribute to psychiatric disorders.

scholarly journals Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Vijay K. Samineni ◽  
Jose G. Grajales-Reyes ◽  
Saranya S. Sundaram ◽  
Judy J. Yoo ◽  
Robert W. Gereau
Keyword(s):  
Neural Circuits ◽  
Periaqueductal Gray ◽  
Gabaergic Neurons ◽  
Cell Type ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Chronic Itch ◽  
Cell Type Specific ◽  
Bidirectional Modulation ◽  
Affective Components

Abstract Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation in mice. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, may encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.

scholarly journals Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray

2018 ◽  
Author(s):  
Vijay K Samineni ◽  
Jose G Grajales-Reyes ◽  
Saranya S Sundaram ◽  
Robert W Gereau
Keyword(s):  
Neural Circuits ◽  
Periaqueductal Gray ◽  
Gabaergic Neurons ◽  
Cell Type ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Chronic Itch ◽  
Cell Type Specific ◽  
Bidirectional Modulation ◽  
Affective Components

Itch is a distinct aversive sensation that elicits a strong urge to scratch. Despite recent advances in our understanding of the peripheral basis of itch, we know very little regarding how central neural circuits modulate acute and chronic itch processing. Here we establish the causal contributions of defined periaqueductal gray (PAG) neuronal populations in itch modulation. Chemogenetic manipulations demonstrate bidirectional modulation of scratching by neurons in the PAG. Fiber photometry studies show that activity of GABAergic and glutamatergic neurons in the PAG is modulated in an opposing manner during chloroquine-evoked scratching. Furthermore, activation of PAG GABAergic neurons or inhibition of glutamatergic neurons resulted in attenuation of scratching in both acute and chronic pruritis. Surprisingly, PAG GABAergic neurons, but not glutamatergic neurons, seem to encode the aversive component of itch. Thus, the PAG represents a neuromodulatory hub that regulates both the sensory and affective aspects of acute and chronic itch.

More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis

Neuroreport ◽  
2016 ◽  
Vol 27 (8) ◽  
pp. 610-616 ◽  
Author(s):  
Hua Liu ◽  
Fang Li ◽  
Chunyan Wang ◽  
Zhiqiang Su
Keyword(s):  
Gabaergic Neurons ◽  
Glutamatergic Neurons

scholarly journals Functional CB1 Receptors Are Broadly Expressed in Neocortical GABAergic and Glutamatergic Neurons

2007 ◽  
Vol 97 (4) ◽  
pp. 2580-2589 ◽  
Author(s):  
Elisa L. Hill ◽  
Thierry Gallopin ◽  
Isabelle Férézou ◽  
Bruno Cauli ◽  
Jean Rossier ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Cannabinoid Receptor ◽  
Physiological Data ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Postsynaptic Currents ◽  
Neocortical Neurons ◽  
Neuronal Types ◽  
Cb1 Antagonist ◽  
Whole Cell Recordings

The cannabinoid receptor CB1 is found in abundance in brain neurons, whereas CB2 is essentially expressed outside the brain. In the neocortex, CB1 is observed predominantly on large cholecystokinin (CCK)-expressing interneurons. However, physiological evidence suggests that functional CB1 are present on other neocortical neuronal types. We investigated the expression of CB1 and CB2 in identified neurons of rat neocortical slices using single-cell RT-PCR. We found that 63% of somatostatin (SST)-expressing and 69% of vasoactive intestinal polypeptide (VIP)-expressing interneurons co-expressed CB1. As much as 49% of pyramidal neurons expressed CB1. In contrast, CB2 was observed in a small proportion of neocortical neurons. We performed whole cell recordings of pyramidal neurons to corroborate our molecular findings. Inhibitory postsynaptic currents (IPSCs) induced by a mixed muscarinic/nicotinic cholinergic agonist showed depolarization-induced suppression of inhibition and were decreased by the CB1 agonist WIN-55212-2 (WIN-2), suggesting that interneurons excited by cholinergic agonists (mainly SST and VIP neurons) possess CB1. IPSCs elicited by a nicotinic receptor agonist were also reduced in the presence of WIN-2, suggesting that neurons excited by nicotinic agonists (mainly VIP neurons) indeed possess CB1. WIN-2 largely decreased excitatory postsynaptic currents evoked by intracortical electrical stimulation, pointing at the presence of CB1 on glutamatergic pyramidal neurons. All WIN-2 effects were strongly reduced by the CB1 antagonist AM 251. We conclude that CB1 is expressed in various neocortical neuronal populations, including glutamatergic neurons. Our combined molecular and physiological data suggest that CB1 widely mediates endocannabinoid effects on glutamatergic and GABAergic transmission to modulate cortical networks.

scholarly journals Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

2009 ◽  
Vol 101 (2) ◽  
pp. 641-654 ◽  
Author(s):  
Sofija Andjelic ◽  
Thierry Gallopin ◽  
Bruno Cauli ◽  
Elisa L. Hill ◽  
Lisa Roux ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Gabaergic Interneuron ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Heterogeneous Cluster ◽  
Glutamatergic Neurons ◽  
Layer V ◽  
Nonpyramidal Neurons ◽  
Layer Vi

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

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