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ELife Feb 2022Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus...
Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus (PBN) and thalamic paraventricular nucleus (PVT) are critical for modulating affective states in mice. However, the functional roles of PBN-PVT projections in modulating affective states remain elusive. Here, we show that PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with PVT neurons. Activation of the PBN-PVT pathway induces robust behaviors associated with negative affective states without affecting nociceptive behaviors. Inhibition of the PBN-PVT pathway reduces aversion-like and fear-like behaviors. Furthermore, the PVT neurons innervated by the PBN are activated by aversive stimulation, and activation of PBN-PVT projections enhances the neuronal activity of PVT neurons in response to the aversive stimulus. Consistently, activation of PVT neurons that received PBN-PVT projections induces anxiety-like behaviors. Thus, our study indicates that PBN-PVT projections modulate negative affective states in mice.
Topics: Animals; Mice; Neurons; Parabrachial Nucleus; Synapses
PubMed: 35167440
DOI: 10.7554/eLife.68372 -
Cell Reports Apr 2023Mechanical allodynia (MA) represents one prevalent symptom of chronic pain. Previously we and others have identified spinal and brain circuits that transmit or modulate...
Mechanical allodynia (MA) represents one prevalent symptom of chronic pain. Previously we and others have identified spinal and brain circuits that transmit or modulate the initial establishment of MA. However, brain-derived descending pathways that control the laterality and duration of MA are still poorly understood. Here we report that the contralateral brain-to-spinal circuits, from Oprm1 neurons in the lateral parabrachial nucleus (lPBN), via Pdyn neurons in the dorsal medial regions of hypothalamus (dmH), to the spinal dorsal horn (SDH), act to prevent nerve injury from inducing contralateral MA and reduce the duration of bilateral MA induced by capsaicin. Ablating/silencing dmH-projecting lPBN neurons or SDH-projecting dmH neurons, deleting Dyn peptide from dmH, or blocking spinal κ-opioid receptors all led to long-lasting bilateral MA. Conversely, activation of dmH neurons or their axonal terminals in SDH can suppress sustained bilateral MA induced by lPBN lesion.
Topics: Mice; Animals; Hyperalgesia; Spinal Cord; Central Nervous System; Spinal Cord Dorsal Horn; Neurons; Hypothalamus
PubMed: 36952340
DOI: 10.1016/j.celrep.2023.112300 -
The Journal of Comparative Neurology Dec 2022Neuropeptide S (NPS) increases wakefulness. A small number of neurons in the brainstem express Nps. These neurons are located in or near the parabrachial nucleus (PB),...
Neuropeptide S (NPS) increases wakefulness. A small number of neurons in the brainstem express Nps. These neurons are located in or near the parabrachial nucleus (PB), but we know very little about their ontogeny, connectivity, and function. To identify Nps-expressing neurons within the molecular framework of the PB region, we used in situ hybridization, immunofluorescence, and Cre-reporter labeling in mice. The primary concentration of Nps-expressing neurons borders the lateral lemniscus at far-rostral levels of the lateral PB. Caudal to this main cluster, Nps-expressing neurons scatter through the PB and form a secondary concentration medial to the locus coeruleus (LC). Most Nps-expressing neurons in the PB region are Atoh1-derived, Foxp2-expressing, and mutually exclusive with neurons expressing Calca or Lmx1b. Among Foxp2-expressing PB neurons, those expressing Nps are distinct from intermingled subsets expressing Cck or Pdyn. Examining Nps Cre-reporter expression throughout the brain identified novel populations of neurons in the nucleus incertus, anterior hypothalamus, and lateral habenula. This information will help focus experimental questions about the connectivity and function of NPS neurons.
Topics: Animals; Mice; Neurons; Brain; In Situ Hybridization; Parabrachial Nucleus; Brain Stem
PubMed: 36036349
DOI: 10.1002/cne.25400 -
Physiology & Behavior Sep 2014The neural basis of food sensory pleasure has become an increasingly studied topic in neuroscience and psychology. Progress has been aided by the discovery of localized... (Review)
Review
The neural basis of food sensory pleasure has become an increasingly studied topic in neuroscience and psychology. Progress has been aided by the discovery of localized brain subregions called hedonic hotspots in the early 2000s, which are able to causally amplify positive affective reactions to palatable tastes ('liking') in response to particular neurochemical or neurobiological stimulations. Those hedonic mechanisms are at least partly distinct from larger mesocorticolimbic circuitry that generates the incentive motivation to eat ('wanting'). In this review, we aim to describe findings on these brain hedonic hotspots, especially in the nucleus accumbens and ventral pallidum, and discuss their role in generating food pleasure and appetite.
Topics: Animals; Brain; Eating; Feeding Behavior; Humans; Motivation; Neurobiology
PubMed: 24874776
DOI: 10.1016/j.physbeh.2014.05.022 -
Neuropharmacology Nov 2014The intricate relationships that associate pain, stress responses and emotional behavior have been well established. Acute stressful situations can decrease nociceptive...
Parabrachial nucleus (PBn) pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the amygdala: implication for the sensory and behavioral effects of pain.
The intricate relationships that associate pain, stress responses and emotional behavior have been well established. Acute stressful situations can decrease nociceptive sensations and conversely, chronic pain can enhance other pain experiences and heighten the emotional and behavioral consequences of stress. Accordingly, chronic pain is comorbid with a number of behavioral disorders including depression, anxiety abnormalities and associated stress-related disorders including post traumatic stress disorder (PTSD). The central nucleus of the amygdala (CeA) represents a convergence of pathways for pain, stress and emotion, and we have identified pituitary adenylate cyclase activating polypeptide (PACAP) immunoreactivity in fiber elements in the lateral capsular division of the CeA (CeLC). The PACAP staining patterns colocalized in part with those for calcitonin gene related peptide (CGRP); anterograde fiber tracing and excitotoxic lesion studies demonstrated that the CeLC PACAP/CGRP immunoreactivities represented sensory fiber projections from the lateral parabrachial nucleus (LPBn) along the spino-parabrachioamygdaloid tract. The same PBn PACAP/CGRP fiber system also projected to the BNST. As in the BNST, CeA PACAP signaling increased anxiety-like behaviors accompanied by weight loss and decreased feeding. But in addition to heightened anxiety-like responses, CeA PACAP signaling also altered nociception as reflected by decreased latency and threshold responses in thermal and mechanical sensitivity tests, respectively. From PACAP expression in major pain pathways, the current observations are novel and suggest that CeA PACAP nociceptive signaling and resulting neuroplasticity via the spino-parabrachioamygdaloid tract may represent mechanisms that associate chronic pain with sensory hypersensitivity, fear memory consolidation and severe behavioral disorders.
Topics: Amygdala; Animals; Anxiety; Calcitonin Gene-Related Peptide; Chronic Disease; Disease Models, Animal; Eating; Male; Neural Pathways; Nociception; Pain; Pain Threshold; Parabrachial Nucleus; Pituitary Adenylate Cyclase-Activating Polypeptide; Random Allocation; Rats, Sprague-Dawley; Stress, Psychological; Weight Loss
PubMed: 24998751
DOI: 10.1016/j.neuropharm.2014.06.022 -
The Journal of Neuroscience : the... Feb 2023Recent findings from our laboratory demonstrated that the rostral nucleus of the solitary tract (rNST) retains some responsiveness to sugars in double-knock-out mice...
Recent findings from our laboratory demonstrated that the rostral nucleus of the solitary tract (rNST) retains some responsiveness to sugars in double-knock-out mice lacking either the T1R1+T1R3 (KO1+3) or T1R2+T1R3 (KO2+3) taste receptor heterodimers. Here, we extended these findings in the parabrachial nucleus (PBN) of male and female KO1+3 mice using warm stimuli to optimize sugar responses and employing additional concentrations and pharmacological agents to probe mechanisms. PBN T1R-independent sugar responses, including those to concentrated glucose, were more evident than in rNST. Similar to the NST, there were no "sugar-best" neurons in KO1+3 mice. Nevertheless, 1000 mm glucose activated nearly 55% of PBN neurons, with responses usually occurring in neurons that also displayed acid and amiloride-insensitive NaCl responses. In wild-type (WT) mice, concentrated sugars activated the same electrolyte-sensitive neurons but also "sugar-best" cells. Regardless of genotype, phlorizin, an inhibitor of the sodium-glucose co-transporter (SGLT), a component of a hypothesized alternate glucose-sensing mechanism, did not diminish responses to 1000 mm glucose. The efficacy of concentrated sugars for driving neurons broadly responsive to electrolytes implied an origin from Type III taste bud cells. To test this, we used the carbonic anhydrase (CA) inhibitor dorzolamide (DRZ), previously shown to inhibit amiloride-insensitive sodium responses arising from Type III taste bud cells. Dorzolamide had no effect on sugar-elicited responses in WT sugar-best PBN neurons but strongly suppressed them in WT and KO1+3 electrolyte-generalist neurons. These findings suggest a novel T1R-independent mechanism for hyperosmotic sugars, involving a CA-dependent mechanism in Type III taste bud cells. Since the discovery of receptors for sugars and artificial sweeteners, evidence has accrued that mice lacking these receptors maintain some behavioral, physiological, and neural responsiveness to sugars. But the substrate(s) has remained elusive. Here, we recorded from parabrachial nucleus (PBN) taste neurons and identified T1R-independent responses to hyperosmotic sugars dependent on carbonic anhydrase (CA) and occurring primarily in neurons broadly responsive to NaCl and acid, implying an origin from Type III taste bud cells. The effectiveness of different sugars in driving these T1R-independent responses did not correlate with their efficacy in driving licking, suggesting they evoke a nonsweet sensation. Nevertheless, these salient responses are likely to comprise an adequate cue for learned preferences that occur in the absence of T1R receptors.
Topics: Animals; Female; Male; Mice; Amiloride; Glucose; Mice, Knockout; Sodium Chloride; Sugars; Taste; Taste Buds
PubMed: 36623875
DOI: 10.1523/JNEUROSCI.1760-22.2023 -
Nature Communications Jan 2021The neural circuitry mediating taste has been mapped out from the periphery to the cortex, but genetic identity of taste-responsive neurons has remained elusive. Here,...
The neural circuitry mediating taste has been mapped out from the periphery to the cortex, but genetic identity of taste-responsive neurons has remained elusive. Here, we describe a population of neurons in the gustatory region of the parabrachial nucleus that express the transcription factor Satb2 and project to taste-associated regions, including the gustatory thalamus and insular cortex. Using calcium imaging in awake, freely licking mice, we show that Satb2 neurons respond to the five basic taste modalities. Optogenetic activation of these neurons enhances taste preferences, whereas chronic inactivation decreases the magnitude of taste preferences in both brief- and long-access taste tests. Simultaneous inactivation of Satb2 and calcitonin gene-related peptide neurons in the PBN abolishes responses to aversive tastes. These data suggest that taste information in the parabrachial nucleus is conveyed by multiple populations of neurons, including both Satb2 and calcitonin gene-related peptide neurons.
Topics: Animals; Calcitonin Gene-Related Peptide; Female; Green Fluorescent Proteins; Male; Matrix Attachment Region Binding Proteins; Mice, Inbred C57BL; Neurons; Parabrachial Nucleus; Physical Stimulation; Taste; Taste Perception; Transcription Factors; Mice
PubMed: 33431851
DOI: 10.1038/s41467-020-20100-8 -
The Journal of Comparative Neurology Aug 2021The parabrachial nucleus (PB) is composed of glutamatergic neurons at the midbrain-hindbrain junction. These neurons form many subpopulations, one of which expresses...
The parabrachial nucleus (PB) is composed of glutamatergic neurons at the midbrain-hindbrain junction. These neurons form many subpopulations, one of which expresses Calca, which encodes the neuropeptide calcitonin gene-related peptide (CGRP). This Calca-expressing subpopulation has been implicated in a variety of homeostatic functions, but the overall distribution of Calca-expressing neurons in this region remains unclear. Also, while previous studies in rats and mice have identified output projections from CGRP-immunoreactive or Calca-expressing neurons, we lack a comprehensive understanding of their efferent projections. We began by identifying neurons with Calca mRNA and CGRP immunoreactivity in and around the PB, including populations in the locus coeruleus and motor trigeminal nucleus. Calca-expressing neurons in the PB prominently express the mu opioid receptor (Oprm1) and are distinct from neighboring neurons that express Foxp2 and Pdyn. Next, we used Cre-dependent anterograde tracing with synaptophysin-mCherry to map the efferent projections of these neurons. Calca-expressing PB neurons heavily target subregions of the amygdala, bed nucleus of the stria terminalis, basal forebrain, thalamic intralaminar and ventral posterior parvicellular nuclei, and hindbrain, in different patterns depending on the injection site location within the PB region. Retrograde axonal tracing revealed that the previously unreported hindbrain projections arise from a rostral-ventral subset of CGRP/Calca neurons. Finally, we show that these efferent projections of Calca-expressing neurons are distinct from those of neighboring PB neurons that express Pdyn. This information provides a detailed neuroanatomical framework for interpreting experimental work involving CGRP/Calca-expressing neurons and opioid action in the PB region.
Topics: Animals; Calcitonin Gene-Related Peptide; Efferent Pathways; Female; Gene Expression; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neurons, Efferent; Parabrachial Nucleus
PubMed: 33715169
DOI: 10.1002/cne.25136 -
Physiological Reports May 2020It is crucial for animals to discriminate between palatable (safe) and aversive (toxic) tastants. The mechanisms underlying neuronal discrimination of taste stimuli...
It is crucial for animals to discriminate between palatable (safe) and aversive (toxic) tastants. The mechanisms underlying neuronal discrimination of taste stimuli remain unclear. We examined relations between taste response properties (spike counts, response duration, and coefficient of variation [CV]) and location of taste-sensitive neurons in the pontine parabrachial nucleus (PBN). Extracellular single units' activity in the PBN of Wistar rats was recorded using multibarrel glass micropipettes under urethane anesthesia. Forty taste-sensitive neurons were classified as NaCl (N)-best (n = 15), NaCl/HCl (NH)-best (n = 14), HCl (H)-best (n = 8), and sucrose (S)-best (n = 3) neurons. The net response to NaCl (15.2 ± 2.3 spikes/s) among the N-best neurons was significantly larger than that among the NH-best (4.5 ± 0.8 spikes/s) neurons. The response duration (4.5 ± 0.2 s) of the N-best neurons to NaCl was significantly longer than that of the NH-best (2.2 ± 0.3 s) neurons. These differences in the spike counts and the response durations between the two neuronal types in the PBN were similar to that previously reported in the rostral nucleus of the solitary tract (rNST). The CVs in the N-best and the NH-best neurons were significantly smaller in the PBN than those in the rNST. Histologically, most N-best neurons (12/13, 92%) were localized to the medial region, while NH-best neurons (11/13, 85%) were primarily found within the brachium conjunctivum. These results suggest that NaCl-specific taste information is transmitted by two distinct neuronal groups (N-best and NH-best), with different taste properties and locations within rNST to PBN tractography. Future studies on the higher order nuclei for taste could reveal more palatable and aversive taste pathways.
Topics: Action Potentials; Animals; Male; Neurons; Parabrachial Nucleus; Rats; Rats, Wistar; Sodium Chloride; Solitary Nucleus; Taste; Taste Perception
PubMed: 32441441
DOI: 10.14814/phy2.14443 -
Science China. Life Sciences Apr 2014The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway, which targets brain regions involved in affective and cognitive... (Review)
Review
The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway, which targets brain regions involved in affective and cognitive processes. Pain and emotions have the capacity to influence each other reciprocally; negative emotions, such as depression and anxiety, increase the risk for chronic pain, which may lead to anxiety and depression. The amygdala is a key-player in the expression of emotions, receives direct nociceptive information from the parabrachial nucleus, and is densely innervated by noradrenergic brain centers. In recent years, the amygdala has attracted increasing interest for its role in pain perception and modulation. In this review, we will give a short overview of structures involved in the pain pathway, zoom in to afferent and efferent connections to and from the amygdala, with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala's role in pain processing and modulation. In addition to the involvement of the amygdala in negative emotions during the perception of pain, this brain structure is also a target site for many neuromodulators to regulate the perception of pain. We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.
Topics: Amygdala; Analgesia; Animals; Anxiety; Brain; Depression; Emotions; Humans; Nociception; Norepinephrine; Pain; Pain Perception
PubMed: 24643418
DOI: 10.1007/s11427-014-4638-x