Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories

Chen, Jane; Campos, Carlos; Jarvie, Brooke C.; Palmiter, Richard D.

doi:10.1016/j.neuron.2018.09.032

Cited by 115 publications

(141 citation statements)

References 44 publications

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“…These findings reinforce the role of projections to the CEA for avoidance learning because only this cohort of mice showed evidence of learning to avoid the light-paired chamber during the RTPA assay. Together, these data suggest that avoidance memory can be elicited by efferent pathways from the elPBN ( Figure 4K), consistent with previous studies Chen et al, 2018;Han et al, 2015;Sato et al, 2015).…”

Section: Resultssupporting

confidence: 92%

Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

Chiang

Nguyen

Papale

et al. 2019

Preprint

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ABSTRACTThe lateral parabrachial nucleus (lPBN) is a major target of spinal projection neurons conveying nociceptive input into supraspinal structures. However, the functional role of distinct lPBN efferents for diverse nocifensive responses have remained largely uncharacterized. Here, we show that two populations of efferent neurons from different regions of the lPBN collateralize to distinct targets. Activation of efferent projections to the ventromedial hypothalamus (VMH) or lateral periaqueductal gray (lPAG) drive escape behaviors, whereas the activation of lPBN efferents to the bed nucleus stria terminalis (BNST) or central amygdala (CEA) generates an aversive memory. Finally, we provide evidence that dynorphin expressing neurons span cytoarchitecturally distinct domains of the lPBN to coordinate these distinct aspects of the nocifensive response.HIGHLIGHTSSpatially segregated neurons in the lPBN collateralize to distinct targets.Distinct output pathways give rise to separate aspects of the pain response.Dynorphin neurons within the lPBN convey noxious information across subdivisions.eTOC BLURBChiang et al. reveal that neurons in spatially segregated regions of the lateral parabrachial nucleus collateralize to distinct targets, and that activation of distinct efferents gives rise to separate components of the nocifensive response.

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Section: Resultssupporting

confidence: 92%

Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

Chiang

Nguyen

Papale

et al. 2019

Preprint

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“…However, OD plasticity still occurs in adult mouse visual cortex, although primarily through potentiation of open eye/ipsilateral responses 21 , suggesting the balance of input between the two eyes is still plastic and may require ongoing maintenance. To determine whether Arc is required for the maintenance of binocular cells in adult binocular V1, we used a floxed Arc line (Arc cKO) mice 22 , that was crossed into the thy1-GCaMP6s line. At P180 we injected either AAV5-hSyn-mCherry (Control) or AAV5-hSyn-mCherry-Cre (Cre) virus into L2/3 of binocular V1.…”

Section: Binocularity In the Adult Visual Cortex Requires Ongoing Maimentioning

confidence: 99%

Experience-dependent development and maintenance of binocular neurons in the mouse visual cortex

Jenks

Shepherd

2019

Preprint

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The normal development of neuronal circuits requires both hard-wired gene expression and experience. Sensory processing, such as vision, is especially sensitive to perturbations in experience. However, the exact contribution of experience to neuronal visual response properties and binocular vision remains unknown. To determine how visual response properties develop in vivo, we used single cell resolution two-photon calcium imaging of mouse binocular visual cortex at multiple time-points after eye opening. Few neurons are binocularly responsive immediately after eye opening and respond solely to either the contralateral or ipsilateral eye. Binocular neurons emerge during development, which requires visual experience, and show specific tuning of visual response properties. As binocular neurons emerge, activity between the two eyes becomes more correlated in the neuropil. Since experience-dependent plasticity requires the expression of activity-dependent genes, we determined whether the plasticity gene Arc mediates the development of normal visual response properties. Surprisingly, rather than mirroring the effects of visual deprivation, mice that lack Arc show increased numbers of binocular neurons during development. Strikingly, removing Arc in adult binocular visual cortex increases the numbers of binocular neurons and recapitulates the developmental phenotype, suggesting cortical circuits that mediate visual processing require ongoing experience-dependent plasticity. Thus, experience is critical for the normal development and maintenance of circuits required to process binocular vision.

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“…This non-specificity occurred despite our using the same antibody as used by others e.g. 39,40 . For the following three reasons, however, we do not view this lack of specificity in the c-fos signal as a major concern for the main findings and interpretation of this paper, i.e., that variations in photostimulation input produce tunable changes in hypoglossal motor output in-vivo and they identify REM sleep specific suppression of net motor excitability and responsivity.…”

Section: Discussionmentioning

confidence: 90%

“…These sections were incubated in the primary antibodies for 24 hrs at 4 °C and in the secondary antibodies for 1 hr at room temperature. The anti-c-Fos antibody (ab190289) has been used and validated 39,40 .…”

Section: Study 2: Experiments Across Sleep and Awake Statesmentioning

confidence: 99%

Measurement and State-Dependent Modulation of Hypoglossal Motor Excitability and Responsivity In-Vivo

Aggarwal

Liu

Montandon

et al. 2020

Sci Rep

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Motoneurons are the final output pathway for the brain's influence on behavior. Here we identify properties of hypoglossal motor output to the tongue musculature. tongue motor control is critical to the pathogenesis of obstructive sleep apnea, a common and serious sleep-related breathing disorder. Studies were performed on mice expressing a light sensitive cation channel exclusively on cholinergic neurons (ChAT-ChR2(H134R)-EYFP). Discrete photostimulations under isoflurane-induced anesthesia from an optical probe positioned above the medullary surface and hypoglossal motor nucleus elicited discrete increases in tongue motor output, with the magnitude of responses dependent on stimulation power (p < 0.001, n = 7) and frequency (P = 0.002, n = 8, with responses to 10 Hz stimulation greater than for 15-25 Hz, P < 0.022). Stimulations during REM sleep elicited significantly reduced responses at powers 3-20 mW compared to non-rapid eye movement (non-REM) sleep and wakefulness (each p < 0.05, n = 7). Response thresholds were also greater in REM sleep (10 mW) compared to non-REM and waking (3 to 5 mW, P < 0.05), and the slopes of the regressions between input photostimulation powers and output motor responses were specifically reduced in REM sleep (P < 0.001). This study identifies that variations in photostimulation input produce tunable changes in hypoglossal motor output in-vivo and identifies REM sleep specific suppression of net motor excitability and responsivity.Obstructive sleep apnea (OSA) is a common and serious breathing disorder with significant clinical, social and economic consequences 1 . OSA is characterized by repeated episodes of upper airway obstruction that occur only during sleep, with the airway obstructions leading to futile breathing efforts, asphyxia, sleep disturbance and other physiological sequalae of medical relevance 2,3 . The root cause of the upper airway obstruction is reduced activity and reflex compensatory responses of the pharyngeal muscles during sleep, whereas in wakefulness the motor activity and responsivity are sufficient to keep the airspace open 4 . Ultimately, state-dependent pharyngeal muscle activity and responsivity of the brainstem motor pools driving these muscles are pivotal to OSA pathophysiology and the phenotypic traits of OSA patients 5-8 .Such state-dependent activity of the pharyngeal musculature is central to OSA pathogenesis, and the hypoglossal motoneuron pool is the source of motor output to the largest of the pharyngeal muscles, the tongue 2,4 . Single unit recordings of tongue motor activity are an experimentally powerful indicator of the discharge patterns and recruitment characteristics of single hypoglossal motoneurons in the medulla that are otherwise inaccessible for investigation [9][10][11][12][13][14][15][16][17][18][19] . One limitation of such single-unit studies, however, is the inability to impose acute, precise and direct control over hypoglossal motor output to interrogate physiological properties relevant to tongue motor control.In the present...

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Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories

Cited by 115 publications

References 44 publications

Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response

Experience-dependent development and maintenance of binocular neurons in the mouse visual cortex

Measurement and State-Dependent Modulation of Hypoglossal Motor Excitability and Responsivity In-Vivo

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