Noradrenergic cross-modular reciprocal inhibition within the locus coeruleus

Davy, Oscar; Perrins, R; Lavigne, Marina; Kremer, Eric J.; Tsaneva‐Atanasova, Krasimira; Ashby, Michael C.; Pickering, Anthony E.

doi:10.1101/2022.09.07.506929

Cited by 4 publications

(7 citation statements)

References 83 publications

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“…While other unknown reasons may contribute to the absence of lateral inhibition, a plausible explanation is that NE released from individual LC/NE neurons is not sufficient to activate α2AR to evoke detectable inhibition on LC/NE neurons at least in our in vitro preparation. A recent study suggests that α2AR-mediated lateral inhibition is a frequency-dependent population-wide phenomenon, which can be readily detected when many neurons are simultaneously activated via an optogenetic approach (Davy et al, 2022). In addition, α2AR-mediated lateral inhibition appears to be a specific network interaction that is prevalent among LC neurons targeting distinct brain regions (module-specific), rather than a non-specific, spatial “surround” inhibition (Davy et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study suggests that α2AR-mediated lateral inhibition is a frequency-dependent population-wide phenomenon, which can be readily detected when many neurons are simultaneously activated via an optogenetic approach (Davy et al, 2022). In addition, α2AR-mediated lateral inhibition appears to be a specific network interaction that is prevalent among LC neurons targeting distinct brain regions (module-specific), rather than a non-specific, spatial “surround” inhibition (Davy et al, 2022). All these could explain why lateral inhibition could be not readily detected at the single-cell level in our dataset where each LC neuron was randomly targeted and individually tested for this type of interaction.…”

Section: Discussionmentioning

confidence: 99%

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Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

McKinney

Jing

et al. 2022

Preprint

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The locus coeruleus (LC) houses the vast majority of noradrenergic neurons in the brain and regulates many fundamental functions. While efferent projections of the LC have been extensively investigated, little is known about its local circuit organization. Here, we performed large-scale multi-patch recordings of LC noradrenergic neurons to profile their morpho-electric properties while simultaneously examining their interactions. LC neurons were diverse and could be classified into two major morpho-electric types. While chemical transmission was not detected, these neurons electrically connected at a rate comparable to many brain regions. Most connections form between dendrites and were restricted to narrowly spaced pairs or small clusters of neurons of the same type. Furthermore, more than two coupled pairs were often identified from individual recording sets that follow a train-like organizational pattern. The assembly of LC neurons follows a spatial and cell type-specific wiring principle that may be imposed by a unique train-like rule.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

McKinney

Jing

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…While other unknown reasons may contribute to the absence of lateral inhibition, a plausible explanation is that NE released from individual LC/NE neurons is not sufficient to activate α2AR to evoke detectable inhibition on LC/NE neurons at least in our in vitro preparation. A recent study suggests that α2AR-mediated lateral inhibition is a frequency-dependent population-wide phenomenon, which can be readily detected when many neurons are simultaneously activated via an optogenetic approach ( Davy et al, 2022 ). In addition, α2AR-mediated lateral inhibition appears to be a specific network interaction that is prevalent among LC neurons targeting distinct brain regions (module-specific), rather than a nonspecific, spatial ‘surround’ inhibition ( Davy et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study suggests that α2AR-mediated lateral inhibition is a frequency-dependent population-wide phenomenon, which can be readily detected when many neurons are simultaneously activated via an optogenetic approach ( Davy et al, 2022 ). In addition, α2AR-mediated lateral inhibition appears to be a specific network interaction that is prevalent among LC neurons targeting distinct brain regions (module-specific), rather than a nonspecific, spatial ‘surround’ inhibition ( Davy et al, 2022 ). All these could explain why lateral inhibition could not be readily detected at the single-cell level in our dataset where each LC neuron was randomly targeted and individually tested for this type of interaction.…”

Section: Discussionmentioning

confidence: 99%

Cellular composition and circuit organization of the locus coeruleus of adult mice

McKinney

Hoskins

et al. 2023

eLife

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The locus coeruleus (LC) houses the vast majority of noradrenergic neurons in the brain and regulates many fundamental functions including fight and flight response, attention control, and sleep/wake cycles. While efferent projections of the LC have been extensively investigated, little is known about its local circuit organization. Here, we performed large-scale multi-patch recordings of noradrenergic neurons in adult mouse LC to profile their morpho-electric properties while simultaneously examining their interactions. LC noradrenergic neurons are diverse and could be classified into two major morpho-electric types. While fast excitatory synaptic transmission among LC noradrenergic neurons was not observed in our preparation, these mature LC neurons connected via gap junction at a rate similar to their early developmental stage and comparable to other brain regions. Most electrical connections form between dendrites and are restricted to narrowly spaced pairs or small clusters of neurons of the same type. In addition, more than two electrically coupled cell pairs were often identified across a cohort of neurons from individual multi-cell recording sets that followed a chain-like organizational pattern. The assembly of LC noradrenergic neurons thus follows a spatial and cell type-specific wiring principle that may be imposed by a unique chain-like rule.

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“…First, exogenously applied NPY can induce widespread recruitment of Y2R-containing efferents outside the LC dendritic zone, with extra-LC contributions accounting for the observed behavioral effects. Instead, we here assess recruitment of local endogenous NPY sources, possibly relying on proximity between pre-and post-synaptic targets, as seen for NE 63 , resulting in targeted effects on LC NE intrinsic excitability and the ensuing Y1R-dependent anxiolysis.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxiety

Riga,

Rademakers,

Wolterink-Donselaar

et al. 2023

Preprint

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Adaptive responses to challenging environments depend on optimal function of the locus coeruleus (LC), the main source of noradrenaline in the brain and primary mediator of the initial stress response. Built-in systems that exert regulatory control over the LC are largely unidentified. A good candidate system is neuropeptide Y (NPY), which is traditionally linked to anxiety-relief. Currently, the endogenous source of NPY to the LC, and how NPY-expressing neurons modulate the noradrenergic system to regulate anxiety remain unclear. We here identify, in mice, a novel NPY-expressing neuronal population (peri-LCNPY) neighboring LC noradrenergic neurons that locally innervates the pericoerulean space. Moreover, we demonstrate that stress engages peri-LCNPY neurons, increasing their excitability. Mimicking peri-LCNPY neuronal activation using ex vivo chemogenetics suppresses LC noradrenergic neuron activity, via an NPY Y1 receptor-mediated mechanism. Furthermore, in vivo chemogenetic stimulation of peri-LCNPY neurons results in Y1R-dependent anxiety-relief. Conversely, inhibiting peri-LCNPY neurons increases anxiety-like behaviors. Together, we establish a causal role for peri-LCNPY-mediated neuromodulation of the LC in the regulation of anxiety, providing novel insights in the endogenous mechanisms underlying adaptive responses to adversity.

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Noradrenergic cross-modular reciprocal inhibition within the locus coeruleus

Cited by 4 publications

References 83 publications

Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

Cellular composition and circuit organization of the locus coeruleus of adult mice

Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxiety

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