In vitro thermosensitivity of rat lateral parabrachial neurons

Xue, Yunfei; Yang, Yong‐Lu; Yu, Tang; Ye, Mengping; Xu, Jianhui; Zeng, Yi-Xin; Zhang, Jie

doi:10.1016/j.neulet.2016.02.058

Cited by 10 publications

(9 citation statements)

References 15 publications

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“…The copyright holder for this preprint this version posted June 12, 2020. ; https://doi.org/10.1101/2020.06.11.138370 doi: bioRxiv preprint 3 are relayed by brain stem neurons the lateral parabrachial (LPB) (16)(17)(18) and reach the thermoregulation center the preoptic area (POA) (4,8,9). Several key types of POA neurons have been identified recently to control different aspects of heatdefense activities (19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Yang

Zhang

et al. 2020

Preprint

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words) 39Heat defense is crucial for survival and fitness, and its dysregulation may result in 40 deaths due to poor management. Transmission of thermosensory signals into 41 hypothalamic thermoregulation centers represent a key layer of regulation in heat 42 defense. However, the mechanism by which these signals are transmitted into the 43 hypothalamus remains poorly understood. Here, we reveal that glutamatergic 44 prodynorphin and cholecystokinin neuron populations in the lateral parabrachial 45 (LPB) are progressively recruited to defend elevated body temperature. These two 46 nonoverlapping neuron types form circuitries with downstream preoptic 47 hypothalamic neurons to inhibit BAT thermogenesis and activate tail vasodilation, 48respectively. Both circuitries are selectively activated by warm temperatures and 49 are required for fever limiting. The prodynorphin circuitry is further required for 50 regulation of energy expenditure and weight homeostasis. Thus, these findings 51 establish that the genetic and functional specificity of heat defense neurons occurs 52 as early as in the LPB and uncover categorical neuron types for encoding two heat 53 defense variables, which may provide targets for treating thermoregulation 54 disorders. 55 56 INTRODUCTION 57Homeostatic control of body temperature during heat defense is crucial for the 58 survival and fitness in mammals. Heat defense-related disorders include 59 heatstroke (1, 2) that causes hundreds of death each year in the US (3), and 60 menopause thermal disequilibrium (MTD) (4, 5) that affects 75% of menopaused 61 women (5, 6). Unfortunately, treatment is very limited against these disorders (3, 62 7), such as physical methods for heatstroke and hormone therapy for MTD, 63 respectively. Heat defense is achieved by precise coordination between dedicated 64 brain pathways and peripheral effector organs (4, 8, 9). Perturbation of these 65 pathways may lead to temperature dysregulation (4, 10), and aggravate obesity 66 and type 2 diabetes (11, 12). Previous findings have suggested that feed-forward 67 temperature signals are detected by thermoreceptors expressed in dorsal root 68 ganglion neurons (13, 14) and are transmitted into the spinal cord (15), which then 69 3 are relayed by brain stem neurons the lateral parabrachial (LPB) (16-18) and reach 70 the thermoregulation center the preoptic area (POA) (4, 8, 9). Several key types of 71 POA neurons have been identified recently to control different aspects of heat-72 defense activities (19)(20)(21)(22)(23)(24)(25)(26)(27). For example, activation of neurons expressing the leptin 73 receptor in the ventromedial preoptic area (VMPO) induces hypothermia along with 74 a reduction of physical activities and energy expenditure (EE) (23). Neurons 75 expressing brain-derived neurotrophic factor/pituitary adenylate cyclase-activating 76 polypeptide (BDNF/PACAP) in the anterior ventromedial preoptic area (VMPO) 77 induce hypothermia, reduce thermogenesis by interscapular brown fat tissues 78 (iBATs), impair nest buildi...

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Section: Introductionmentioning

confidence: 99%

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Yang

Zhang

et al. 2020

Preprint

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“…To study the effects of PGE 2 on the spontaneous firing activity and thermosensitivity of LPBN neurons, the patch clamp test was performed as previously described [27, 28]. After pentobarbital anesthesia, the rats were decapitated.…”

Section: Methodsmentioning

confidence: 99%

“…The LPBN was visually identified as a crescent-shaped lucent region at the dorsolateral surface of the pons, bordered by the ventral spinocerebellar tract dorsally and the superior cerebellar peduncle ventrally. The 3 LPBN subnuclei were defined by their relationship to the superior cerebellar peduncle [27, 28, 38]. The Pulse + Pulsefit software (HEKA) was used for data acquisition and analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Thermosensitivity (impulses [imp]/s/°C) was defined by the slope of the linear regression line (known as the thermal coefficient m) plotted by the firing rate as a function of temperature. As in previous studies [27, 28], the thermal coefficient of warm-sensitive neurons was set at ≥0.8 imp/s/°C and that of cold-sensitive neurons at ≤−0.6 imp/s/°C, while the others were identified as temperature-insensitive. After characterizing the thermosensitivity of each neuron, we tested its response to PGE 2 (1 μM).…”

Section: Methodsmentioning

confidence: 99%

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The Role of Prostaglandin E2 Synthesized in Rat Lateral Parabrachial Nucleus in LPS-Induced Fever

Cheng

Zeng

et al. 2021

Neuroendocrinology

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Introduction: The lateral parabrachial nucleus (LPBN) is considered to be a brain site of the pyrogenic action of prostaglandin (PG) E2 outside of the preoptic area. Yet, the role of the LPBN in fever following a systemic immune challenge remains poorly understood. Methods: We examined the expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) in the LPBN after the intraperitoneal injection of lipopolysaccharide (LPS). We investigated the effects of LPBN NS-398 (COX-2 inhibitor) on LPS-induced fever, the effects of direct LPBN PGE2 administration on the energy expenditure (EE), brown adipose tissue (BAT) thermogenesis, neck muscle electromyographic activity and tail temperature, and the effects of PGE2 on the spontaneous firing activity and thermosensitivity of in vitro LPBN neurons in a brain slice. Results: The COX-2 and mPGES-1 enzymes were upregulated at both mRNA and protein levels. The microinjection of NS-398 in the LPBN attenuated the LPS-induced fever. Direct PGE2 administration in the LPBN resulted in a febrile response by a coordinated response of increased EE, BAT thermogenesis, shivering, and possibly decreased heat loss through the tail. The LPBN neurons showed a clear anatomical distinction in the firing rate response to PGE2, with the majority of PGE2-excited or -inhibited neurons being located in the external lateral or dorsal subnucleus of the LPBN, respectively. However, neither the firing rate nor the thermal coefficient response to PGE2 showed any difference between warm-sensitive, cold-sensitive, and temperature-insensitive neurons in the LPBN. Conclusions: PGE2 synthesized in the LPBN was at least partially involved in LPS-induced fever via its different modulations of the firing rate of neurons in different LPBN subnuclei.

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“…Cold and warm cutaneous signals are transmitted to the respective dorsal root ganglia, which output this information to the dorsal horn. The lateral parabrachial (LPB) nuclei have local thermosensory functions as POA and play a pivotal role in transmitting cutaneous thermosensory signals from the dorsal horn to the POA (Nakamura & Morrison, ; Xue et al ., ). The external lateral subnucleus (LPBel) and dorsal subnucleus of the LPB nucleus receive cold and warm signal inputs from the dorsal horn, respectively (Morrison & Nakamura, ).…”

Section: Introductionmentioning

confidence: 97%

Arginine vasopressin differentially modulates GABAergic synaptic transmission onto temperature‐sensitive and temperature‐insensitive neurons in the rat preoptic area

Sun

et al. 2018

Eur J of Neuroscience

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The preoptic area (POA) of the hypothalamus, containing temperature-sensitive and temperature-insensitive neurons, plays a key role in specific thermoregulatory responses. Although arginine vasopressin (AVP) has been shown to induce hypothermia by increasing the firing activities of warm-sensitive neurons and decreasing those of cold-sensitive and temperature-insensitive neurons, the effects of AVP on POA GABAergic transmission remain unknown. Herein, inhibitory postsynaptic currents (IPSCs) of temperature-sensitive and temperature-insensitive neurons in POA slices were recorded using whole-cell patch clamp. By monitoring changes in GABAergic transmission during AVP treatment, we showed that AVP decreased the amplitudes and frequencies of spontaneous IPSCs in mostly warm-sensitive neurons and in some temperature-insensitive neurons but increased these parameters in other temperature-insensitive neurons. The IPSC amplitude was reduced for only cold-sensitive neurons. RT-PCR and Western blot analyses further confirmed the POA expression of V1a receptors and GABA receptors, including the subunits α1, α2, α3, β2, β3 and γ2. The effects of AVP on IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent on G proteins and intracellular Ca . AVP-mediated modulation was associated with changes in the kinetic parameters (decay time, 10-90% rise time, half-width). Together, these results suggest that AVP, acting via V1a receptors but not V1b receptors, differentially modulates GABAergic synaptic transmission and fine-tunes the firing activities of temperature-sensitive and temperature-insensitive neurons in the rat POA.

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In vitro thermosensitivity of rat lateral parabrachial neurons

Cited by 10 publications

References 15 publications

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

Parabrachial neuron types categorically encode thermoregulation variables during heat defense

The Role of Prostaglandin E<sub>2</sub> Synthesized in Rat Lateral Parabrachial Nucleus in LPS-Induced Fever

Arginine vasopressin differentially modulates GABAergic synaptic transmission onto temperature‐sensitive and temperature‐insensitive neurons in the rat preoptic area

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