Brain‐wide mapping of presynaptic inputs to basolateral amygdala neurons

Morikawa, Shota; Katori, Kazuki; Takeuchi, Haruki; Ikegaya, Yuji

doi:10.1002/cne.25149

Cited by 14 publications

(9 citation statements)

References 94 publications

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“…Six days post-injection, we examined sections of the entire brain to quantify the location and the relative number of inputs neurons (mCherry+) ( Figure S8E ). Labelled brain regions directly projecting onto BLA-to-NAc and BLA-to-CeA neurons were similar to those previously reported (31,32) ( Figure S8F,G ). Comparing CORT with Veh-treated mice, we established a brain map of differential contributions of input regions, revealing which brain circuits exhibited distinct connectivity patterns after depressive state induction ( Figure 5D and Figure S8F,G ).…”

Section: Resultssupporting

confidence: 88%

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

Bigot

Badts

Benchetrit

et al. 2023

Preprint

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Negative emotional bias is an essential hallmark of depression reflected by negative shift in hedonic valence assignment to emotional stimuli. Pleasant cues become less attractive and unpleasant ones more aversive. Given the crucial role of amygdala in valence coding, we hypothesize that specific basolateral amygdala (BLA) circuits alterations might support negative emotional bias associated with depressive states. Using a translational assay, we evaluate odor valence assignment in an animal model for depression chronically administered by corticosterone (CORT). We show spontaneous negative bias in depressive-like mice that attribute more negative valences for both attractive and aversive odors, mimicking thus the bias observed in depressed bipolar patients. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity and chemogenetics experiments, we find that the CORT treatment reduces BLA-to-nucleus accumbens (NAc) neuronal activity and increases BLA-to-central amygdala activity, circuits respectively known to be involved in positive and negative valence encoding. Alterations in presynaptic connectivity of BLA-projecting neurons accompany these activity shifts. Interestingly, inputs from the paraventricular thalamus nucleus (PVT) towards BLA-to-NAc neurons are reduced in CORT-treated mice. Finally, chemogenetically activating the BLA-to-NAc circuit attenuates the negative bias in CORT-treated mice as well as the depressive-like phenotype, similarly than Fluoxetine antidepressant treatment. Altogether, we demonstrate that depressive states are associated with negative emotional bias both in human and mice. This bias is supported by activity shifts of specific BLA circuits along with durable presynaptic connectivity changes, but it could be alleviated by antidepressant drug or activity manipulation of altered BLA circuit.

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Section: Resultssupporting

confidence: 88%

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

Bigot

Badts

Benchetrit

et al. 2023

Preprint

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“…2). The BLA normally receives multiple inputs from various brain regions including prefrontal, piriform, auditory, associative, and insular cortices 53,54 . However, unlike in primates, the BLA does not normally receive any direct input from primary sensory cortex in rodents.…”

Section: Discussionmentioning

confidence: 99%

ASD gene Bcl11a regulates subcellular RNA localization, associative circuitry, and social behavior

Durak

Kim

Tillman

et al. 2022

Preprint

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Precise, area-specific connectivity of interhemispheric callosal projection neurons (CPN) in the cerebral cortex is critical for sensory, associative, and behavioral functions. CPN circuitry, which connects and integrates the cerebral hemispheres via the corpus callosum, is centrally implicated in autism spectrum disorder (ASD) and intellectual disability (ID). Though transcriptional controls regulating CPN subtype and areal development are partially understood, downstream subcellular molecular machinery that implements CPN circuitry is essentially unknown. Here, we identify that the highly penetrant ASD/ID risk gene Bcl11a/Ctip1 is critical developmentally for appropriate and precise areal targeting of superficial layer CPN (CPNSL) projections, and that its deletion strikingly re-routes some CPNSL projections subcortically, causes dramatic disruption to subcellular CPNSL growth cone (GC) molecular machinery, and disrupts social behavior and cognition in mice. CPNSL-specific embryonic deletion of Bcl11a causes loss of correct homotopic targeting in the contralateral cortex, re-routes a substantial proportion of axonal projections through the anterior commissure, and induces strikingly aberrant, but specific and precise, projections to the basolateral amygdala. Importantly, bilateral deletion of Bcl11a from CPNSL results in abnormal social behavior and working memory. Mechanistically, we identify dysregulation of the CPNSL axonal GC-localized transcriptome in Bcl11a nulls, due to either aberrant transcription or trafficking of individual transcripts. These molecular mis-localizations disrupt axon guidance and CPNSL circuitry formation. Together, this work identifies critical functions for Bcl11a in CPNSL axonal connectivity, development of functional associative-social circuitry, and regulation of subtype-specific subcellular molecular machinery in vivo, revealing novel GC-localized transcripts that regulate precise axonal targeting and circuit formation. These results elucidate development and ASD/ID disease-related circuit disruption of CPNSL, and the importance of understanding circuit-specific subcellular molecular machinery by neurons.

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“…The regions supplying the densest afferents to the BLA include the thalamus, ventral hippocampus, dorsal raphe nucleus, posterior intralaminar nucleus, medial geniculate nucleus, ventral tegmental area, nucleus accumbens, and cortical areas including the prefrontal cortical areas and other sensory cortical regions ( Steinbusch, 1981 ; Bocchio et al, 2016 ; Fu et al, 2020 ; Hintiryan et al, 2021 ; Morikawa et al, 2021 ). Each of these input pathways relays different forms of state, motivational, or sensory information to the BLA.…”

Section: Amygdala Overviewmentioning

confidence: 99%

Dynorphin/kappa opioid receptor system regulation on amygdaloid circuitry: Implications for neuropsychiatric disorders

Limoges

Yarur

Tejeda

2022

Front. Syst. Neurosci.

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Amygdaloid circuits are involved in a variety of emotional and motivation-related behaviors and are impacted by stress. The amygdala expresses several neuromodulatory systems, including opioid peptides and their receptors. The Dynorphin (Dyn)/kappa opioid receptor (KOR) system has been implicated in the processing of emotional and stress-related information and is expressed in brain areas involved in stress and motivation. Dysregulation of the Dyn/KOR system has also been implicated in various neuropsychiatric disorders. However, there is limited information about the role of the Dyn/KOR system in regulating amygdala circuitry. Here, we review the literature on the (1) basic anatomy of the amygdala, (2) functional regulation of synaptic transmission by the Dyn/KOR system, (3) anatomical architecture and function of the Dyn/KOR system in the amygdala, (4) regulation of amygdala-dependent behaviors by the Dyn/KOR system, and (5) future directions for the field. Future work investigating how the Dyn/KOR system shapes a wide range of amygdala-related behaviors will be required to increase our understanding of underlying circuitry modulation by the Dyn/KOR system. We anticipate that continued focus on the amygdala Dyn/KOR system will also elucidate novel ways to target the Dyn/KOR system to treat neuropsychiatric disorders.

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Brain‐wide mapping of presynaptic inputs to basolateral amygdala neurons

Cited by 14 publications

References 94 publications

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

ASD gene Bcl11a regulates subcellular RNA localization, associative circuitry, and social behavior

Dynorphin/kappa opioid receptor system regulation on amygdaloid circuitry: Implications for neuropsychiatric disorders

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