A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning

Giovanniello, Jacqueline; Yu, Kai; Furlan, Alessandro; Nachtrab, Gregory; Sharma, Radhashree; Chen, Xiaoke; Li, Bo

doi:10.1523/jneurosci.2090-20.2020

Cited by 33 publications

(25 citation statements)

References 65 publications

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“…Recent literature emphasized that PV + neurons are at the intersection of motor-anxiety circuits (Sztainberg et al, 2011; Hunt et al, 2018; Giovanniello et al, 2020); we do not currently know the downstream targets that mediate the anxiety-related response. As the STN does not mediate this anxiety-related response, other descending pathways such as the direct projections to the raphe (Pollak Dorocic et al, 2014) or their indirect projection to the habenula via the internal globus pallidus (Smith et al, 1998; Wallace et al, 2017) could be involved.…”

Section: Discussionmentioning

confidence: 96%

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

Cherian

Cui

Pamukcu

et al. 2020

Preprint

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We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the GPe: they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1+ class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1+ classes. By combining optogenetics,, and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highlighted the dissociable roles of GPe neurons in regulating movement and anxiety. We concluded that Npr3+ neurons and Kcng4+ neurons are distinct subclasses of Npas1+ neurons and PV+ neurons, respectively. Finally, by examining local collateral connectivity, we inferred the circuit mechanisms involved in the motor patterns observed with optogenetic perturbations. In summary, by identifying mouse lines that allow for manipulations of GPe neuron subtypes, we created new opportunities for interrogations of cellular and circuit substrates that can be important for motor function and dysfunction.

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Section: Discussionmentioning

confidence: 96%

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

Cherian

Cui

Pamukcu

et al. 2020

Preprint

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“…Recent literature emphasized that PV + neurons are at the intersection of motor-anxiety circuits (Sztainberg et al, 2011;Hunt et al, 2018;Giovanniello et al, 2020); we do not currently know the downstream targets that mediate the anxiety-related response. As the STN does not mediate this anxiety-related response, other descending pathways such as the direct projections to the raphe (Pollak Dorocic et al, 2014) or their indirect projection to the habenula via the internal globus pallidus (Smith et al, 1998;Wallace et al, 2017) could be involved.…”

Section: Beyond Go and No-go?mentioning

confidence: 95%

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

et al. 2021

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Author contributions SC and BLB performed histological analysis. SC, QC, IYMC, HSX, YZ, HM, ZAA, and XD surveyed the intrinsic properties. QC, HMH, XD, YZ, and CJW examined the local connectivity. AP, QC, SR, and NJJ conducted the behavioral studies. IYMC developed the machine learning analysis pipeline. YC and SMB provided expertise for neuron classification. CSC wrote the manuscript with input from all co-authors. All authors reviewed and edited the manuscript. CSC designed, directed, and supervised the project.

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“…In addition, cellular changes in the amygdala have been reported in ASD (Amaral et al, 2008). In a recent study (Giovanniello et al, 2020), we found that a subpopulation of neurons in the CeA send direct projections to the GPe, and the CeA-GPe pathway conveys US information and controls learning during fear conditioning. In the current study, we found that an enhanced excitatory drive onto GPe-projecting CeA neurons parallels the anxiety phenotypes of female 16p11.2 del /+ mice.…”

Section: Discussionmentioning

confidence: 89%

“…We recently identified a pathway from the CeA to the globus pallidus externa (GPe), which conveys information of the US and is critical for learning in fear conditioning (Giovanniello et al, 2020). Importantly, optogenetic activation of the CeA-GPe pathway increases fear generalization whereby animals increase their freezing to CS–.…”

Section: Resultsmentioning

confidence: 99%

Sex-specific stress-related behavioral phenotypes and central amygdala dysfunction in a mouse model of 16p11.2 microdeletion

Giovanniello

Ahrens

et al. 2020

Preprint

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Substantial evidence indicates that a microdeletion on human chromosome 16p11.2 is linked to neurodevelopmental disorders including autism spectrum disorders (ASD). Carriers of this deletion show divergent symptoms besides the core features of ASD, such as anxiety and emotional symptoms. The neural mechanisms underlying these symptoms are poorly understood. Here we report mice heterozygous for a deletion allele of the genomic region corresponding to the human 16p11.2 microdeletion locus (i.e., the ‘16p11.2 del/+ mice’) have sex-specific anxiety-related behavioral and neural circuit changes. We found that female, but not male 16p11.2 del/+ mice showed enhanced fear generalization – a hallmark of anxiety disorders – after auditory fear conditioning, and displayed increased anxiety-like behaviors after physical restraint stress. Notably, such sex-specific behavioral changes were paralleled by an increase in activity in central amygdala neurons projecting to the globus pallidus in female, but not male 16p11.2 del/+ mice. Together, these results reveal female-specific anxiety phenotypes related to 16p11.2 microdeletion syndrome and a potential underlying neural circuit mechanism. Our study therefore identifies previously underappreciated sex-specific behavioral and neural changes in a genetic model of 16p11.2 microdeletion syndrome, and highlights the importance of investigating female-specific aspects of this syndrome for targeted treatment strategies.

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A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning

Cited by 33 publications

References 65 publications

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

Dissociable Roles of Pallidal Neuron Subtypes in Regulating Motor Patterns

Sex-specific stress-related behavioral phenotypes and central amygdala dysfunction in a mouse model of 16p11.2 microdeletion

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