scholarly journals Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs

2015 ◽  
Vol 308 (12) ◽  
pp. R1045-R1061 ◽  
Author(s):  
Joseph M. Santin ◽  
Lynn K. Hartzler
Keyword(s):  
Locus Coeruleus ◽  
Brain Slices ◽  
Neuronal Firing ◽  
Spontaneous Firing ◽  
Breathing Control ◽  
Cation Current ◽  
Voltage Clamp Analysis ◽  
Physiol Regul Integr Comp ◽  
Hyperpolarization Activated Current

Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current ( Ih) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451–R1464, 2013). This suggests an unlikely role for Ih in generating cold activation, but led us to hypothesize that inhibition of Ih by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs+ (an Ih antagonist) to isolate the role of Ih in spontaneous firing and cold activation in neurons recorded with either control or Ih agonist (cyclic AMP)-containing artificial intracellular fluid. Ih did not contribute to the membrane potential ( Vm) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits Ih, its lack of involvement in setting baseline firing and Vm precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to Ih activation. Our hypothesis was supported when the starting level of Ih was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of Ih facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net Vm response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of Ih activation state on neuronal firing varies in the poikilothermic neuronal environment.

scholarly journals Role of the Hyperpolarization‐Activated Cation Current ( I h ) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

2003 ◽  
Vol 552 (1) ◽  
pp. 135-148 ◽  
Author(s):  
Makoto Funahashi ◽  
Yoshihiro Mitoh ◽  
Atsushi Kohjitani ◽  
Ryuji Matsuo
Keyword(s):  
Rat Brain ◽  
Area Postrema ◽  
Brain Slices ◽  
Pacemaker Activity ◽  
Cation Current

Extranuclear dendrites of locus coeruleus neurons: activation by glutamate and modulation of activity by alpha adrenoceptors

1995 ◽  
Vol 74 (6) ◽  
pp. 2427-2436 ◽  
Author(s):  
A. Ivanov ◽  
G. Aston-Jones
Keyword(s):  
Firing Rate ◽  
Locus Coeruleus ◽  
Discharge Rate ◽  
Brain Slices ◽  
Spontaneous Discharge ◽  
Evoked Responses ◽  
Spontaneous Firing ◽  
Alpha Adrenoceptors ◽  
Bath Application ◽  
Spontaneous Firing Rate

1. Locus coeruleus (LC) neurons were recorded extracellularly and intracellularly in rat brain slices. Effects of glutamate applied to the area of distal extranuclear LC dendrites, and of alpha-2 adrenoceptors applied in the bath, were determined on activity of these cells. 2. Glutamate applied to the area of distal dendrites potently activated LC neurons. These responses were not blocked by either 1 microM tetrodotoxin or 2 mM Co(2+)-10 mM Mg2+. This indicates that glutamate acting directly on distal dendrites can potently activate LC neurons. 3. Bath application of the alpha-2 adrenoceptor antagonists yohimbine (1 microM) or idazoxan (1 microM) significantly increased responses of LC neurons evoked by dendritic glutamate application. These antagonist treatments also transiently decreased, and then increased, spontaneous discharge activity in LC neurons. 4. Alterations in spontaneous and glutamate-evoked activities after blockade of alpha-2 adrenoreceptors were not observed in LC neurons of reserpinized rats. This indicates that the altered LC activity and responsiveness to glutamate following alpha-2 antagonist treatment in nonreserpinized slices are mediated via blockade of effects of endogenously released noradrenaline. 5. The alpha-1 antagonist prazosin (1 microM) caused a small but reliable decrease in the spontaneous firing rate of LC neurons. After prazosin pretreatment, alpha-2 antagonists did not evoke the expected delayed increase in LC spontaneous firing and response to glutamate application. These results indicate that activation of alpha-1 adrenoceptors may contribute to the delayed increase in excitability of LC neurons after alpha-2 antagonist administration. The possible roles of alpha-1 and alpha-2 adrenoreceptors in regulation of spontaneous discharge rate and glutamate-evoked responses in LC neurons are discussed.

scholarly journals ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines

2018 ◽  
Author(s):  
Shu-Xia Cao ◽  
Ying Zhang ◽  
Xing-Yue Hu ◽  
Bin Hong ◽  
Peng Sun ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Critical Role ◽  
Anxiety And Depression ◽  
Spontaneous Firing ◽  
Noradrenergic Neurons ◽  
Neuronal Function ◽  
Conditional Deletion ◽  
Manic Depressive ◽  
Deficient Mice

Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of manic-depressive psychosis (MDP). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to MDP; however, how ErbB4 regulates NE neuronal function and contributes to MDP pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, ErbB4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder.

scholarly journals ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Shu-Xia Cao ◽  
Ying Zhang ◽  
Xing-Yue Hu ◽  
Bin Hong ◽  
Peng Sun ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Locus Coeruleus ◽  
Critical Role ◽  
Anxiety And Depression ◽  
Spontaneous Firing ◽  
Noradrenergic Neurons ◽  
Neuronal Function ◽  
Conditional Deletion ◽  
Deficient Mice

Dysfunction of the noradrenergic (NE) neurons is implicated in the pathogenesis of bipolar disorder (BPD). ErbB4 is highly expressed in NE neurons, and its genetic variation has been linked to BPD; however, how ErbB4 regulates NE neuronal function and contributes to BPD pathogenesis is unclear. Here we find that conditional deletion of ErbB4 in locus coeruleus (LC) NE neurons increases neuronal spontaneous firing through NMDA receptor hyperfunction, and elevates catecholamines in the cerebrospinal fluid (CSF). Furthermore, Erbb4-deficient mice present mania-like behaviors, including hyperactivity, reduced anxiety and depression, and increased sucrose preference. These behaviors are completely rescued by the anti-manic drug lithium or antagonists of catecholaminergic receptors. Our study demonstrates the critical role of ErbB4 signaling in regulating LC-NE neuronal function, reinforcing the view that dysfunction of the NE system may contribute to the pathogenesis of mania-associated disorder.

scholarly journals Alternative splicing of auxiliary β2-subunits stabilizes Cav2.3 Ca2+ channel activity in continuously active midbrain dopamine neurons

2021 ◽  
Author(s):  
Anita Siller ◽  
Nadja T. Hofer ◽  
Giulia Tomagra ◽  
Nicole Wiederspohn ◽  
Simon Hess ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Splice Variants ◽  
Brain Slices ◽  
Physiological Role ◽  
Neuronal Firing ◽  
Dopamine Neurons ◽  
Channel Activity ◽  
Channel Inactivation ◽  
Midbrain Dopamine

AbstractIn dopaminergic (DA) substantia nigra (SN) neurons Cav2.3 R-type Ca2+-currents contribute to somatodendritic Ca2+-oscillations. These may contribute to the selective degeneration of these neurons in Parkinson’s disease (PD) since Cav2.3-knockout is neuroprotective in a PD mouse model. However, the typical Cav2.3 gating would predict complete channel inactivation during SN DA neuronal firing. Here we show that in tsA-201-cells the membrane-anchored β2-splice variants β2a and β2e stabilize Cav2.3 gating properties allowing sustained Cav2.3 availability during simulated pacemaking and enhanced Ca2+-currents during bursts. We confirmed the expression of β2a and β2e-subunits in the SN and identified SN DA neurons. Patch-clamp recordings of SN DA neurons in mouse brain slices revealed R-type Ca2+-currents similar to β2a- or β2e-stabilized Cav2.3-currents and recordings in cultured murine DA neurons confirmed their activity during pacemaking. Taken together, our data support an important (patho)physiological role of β-subunit alternative splicing for Cav2.3 Ca2+-signaling in highly vulnerable SN DA neurons.

Role of Vasopressin in the Cardiovascular Response to Stimulation of the Locus Coeruleus*

Endocrinology ◽  
1986 ◽  
Vol 118 (5) ◽  
pp. 1829-1834 ◽  
Author(s):  
KATHLEEN H. BERECEK ◽  
TERRI N. MITCHUM
Keyword(s):  
Locus Coeruleus ◽  
Cardiovascular Response ◽  
Stimulation Of

scholarly journals The role of Ca2+ in the protoveratrine-induced release of γ-aminobutyrate from rat brain slices

1980 ◽  
Vol 190 (2) ◽  
pp. 333-339 ◽  
Author(s):  
M C W Minchin
Keyword(s):  
Cerebral Cortex ◽  
Rat Brain ◽  
Dose Response ◽  
Transmitter Release ◽  
Response Curve ◽  
Brain Slices ◽  
Veratrum Alkaloids ◽  
Similar Dose ◽  
22Na Uptake

1. Protoveratrine A increased the release of gamma-amino[3H]butyrate from small slices of rat cerebral cortex. This effect increased with increasing protoveratrine concentration, reaching a maximum at 100 microM. 2. Removal of Ca2+ from the superfusing medium did not change the increase in release due to 10 microM-protoveratrine; however, the Ca2+ antagonists, compound D-600, La3+, Mn2+, Mg2+ and also high Ca2+ concentration inhibited the effect of the alkaloid, as did procaine. 3. Protoveratrine A increased the uptake of 22Na+ into the slices with a similar dose-response curve to that found for gamma-aminobutyrate release. For the most part, the substances that inhibited protoveratrine-stimulated gamma-aminobutyrate release also inhibited 22Na+ uptake, although the correlation was not perfect. 4. Although extracellular Ca2+ is not required for protoveratrine-induced gamma-aminobutyrate release, an increase in Na+ influx that is susceptible to inhibition by some Ca2+ antagonists does appear to be associated with this phenomenon. However, the possibility remains that changes in the free intracellular Ca2+ concentration may be important for transmitter release induced by depolarizing veratrum alkaloids.

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