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 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 Neuronal control of suppression, initiation and completion of egg deposition in Drosophila melanogaster

2021 ◽  
Author(s):  
Cristina Oliveira-Ferreira ◽  
Miguel Gaspar ◽  
Maria Luisa Vasconcelos
Keyword(s):  
Cholinergic Neurons ◽  
Egg Laying ◽  
Glutamatergic Neurons ◽  
Neuronal Populations ◽  
Motor Circuits ◽  
Neuronal Control ◽  
Egg Deposition ◽  
Complex Motor ◽  
A Site

Egg-laying in Drosophila is the product of post-mating physiological and behavioural changes that culminate in a stereotyped sequence of actions. While egg-laying behaviour has been mostly used as a system to understand the neuronal basis of decision making in the context of site selection, it harbours a great potential as a paradigm to uncover how, once a site is selected, the appropriate motor circuits are organized and activated to deposit an egg. To study this programme, we first describe the different stages of the egg-laying programme and the specific actions associated with each stage. Using a combination of neuronal activation and silencing experiments we characterize the role of three distinct neuronal populations in the abdominal ganglion with different contributions to the egg deposition motor elements. Specifically, we identify a subset of glutamatergic neurons and a subset of cholinergic neurons that promote the initiation and completion of egg expulsion respectively, while a subset of GABAergic neurons suppresses egg-laying. This study provides insight into the organization of neuronal circuits underlying complex motor behaviour.

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.

scholarly journals Sleep and Motor Control by a Basal Ganglia Circuit

2018 ◽  
Author(s):  
Danqian Liu ◽  
Chenyan Ma ◽  
Weitong Zheng ◽  
Yuanyuan Yao ◽  
Yang Dan
Keyword(s):  
Motor Control ◽  
Basal Ganglia ◽  
Nrem Sleep ◽  
Gabaergic Neurons ◽  
Emg Activity ◽  
Glutamatergic Neurons ◽  
Locomotor Movement ◽  
Cell Groups ◽  
Major Criterion

AbstractFrom invertebrates to humans, a defining feature of sleep is behavioral immobility(Campbell and Tobler, 1984; Hendricks et al., 2000; Shaw et al., 2000). In mammals, diminished electromyographic (EMG) activity is a major criterion for both rapid eye movement (REM) and non-REM (NREM) sleep. However, the relationship between sleep and motor control at the neuronal level remains poorly understood. Here we show that regions of the basal ganglia long known to be essential for motor suppression also play a key role in sleep generation. Optogenetic or chemogenetic activation of GABAergic neurons in mouse substantia nigra pars reticulata (SNr) strongly increased both REM and NREM sleep, whereas their inactivation suppressed sleep and increased wakefulness. Analysis of natural home-cage behavior showed that mice transition sequentially through several behavioral states: locomotion, non-locomotor movement, quiet wakefulness, and sleep. Activation/inactivation of SNr neurons promoted/suppressed sleep by biasing the direction of progression through the natural behavioral sequence. Virus-mediated circuit tracing showed that SNr GABAergic neurons project to multiple wake-promoting monoaminergic cell groups in addition to the thalamus and mesencephalic locomotor region, and activating each projection promoted sleep. Within the thalamus, direct optogenetic inactivation of glutamatergic neurons is sufficient to enhance sleep, but the effect is largely restricted to the regions receiving SNr projection. Furthermore, a major source of excitatory inputs to the SNr is the subthalamic nucleus (STN), and activation of neurotensin-expressing glutamatergic neurons in the STN also promoted sleep. Together, these results demonstrate a key role of the STN-SNr basal ganglia pathway in sleep generation and reveal a novel circuit mechanism linking sleep and motor control.

Quantitative accuracy of serotonergic neurotrans-mission imaging with high-resolution 123I SPECT

2004 ◽  
Vol 43 (06) ◽  
pp. 185-189 ◽  
Author(s):  
J. T. Kuikka
Keyword(s):  
High Resolution ◽  
Scatter Correction ◽  
Region Of Interest ◽  
Binding Potential ◽  
Partial Volume ◽  
Therapeutic Drugs ◽  
Quantitative Accuracy ◽  
Critical Error ◽  
Statistical Noise

Summary Aim: Serotonin transporter (SERT) imaging can be used to study the role of regional abnormalities of neurotransmitter release in various mental disorders and to study the mechanism of action of therapeutic drugs or drugs’ abuse. We examine the quantitative accuracy and reproducibility that can be achieved with high-resolution SPECT of serotonergic neurotransmission. Method: Binding potential (BP) of 123I labeled tracer specific for midbrain SERT was assessed in 20 healthy persons. The effects of scatter, attenuation, partial volume, mis-registration and statistical noise were estimated using phantom and human studies. Results: Without any correction, BP was underestimated by 73%. The partial volume error was the major component in this underestimation whereas the most critical error for the reproducibility was misplacement of region of interest (ROI). Conclusion: The proper ROI registration, the use of the multiple head gamma camera with transmission based scatter correction introduce more relevant results. However, due to the small dimensions of the midbrain SERT structures and poor spatial resolution of SPECT, the improvement without the partial volume correction is not great enough to restore the estimate of BP to that of the true one.

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