Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology

Aston‐Jones, Gary; Shipley, MT; Chouvet, Guy; Ennis, Matthew; Bockstaele, Elisabeth Van; Pieribone, Vincent A.; Shiekhattar, Ramin; Akaoka, H.; Drolet, Guy; Astier, Bernadette; Charléty, P. J.; Valentino, Rita J.; Williams, John T.

doi:10.1016/s0079-6123(08)63799-1

Cited by 482 publications

(299 citation statements)

References 101 publications

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“…A recent report by Krahl et al (40) demonstrated the importance of the locus coeruleus for the anticonvulsant effects of vagal nerve stimulation, by showing that lesions of the locus coeruleus suppressed the anticonvulsant effects of vagal nerve stimulation. The locus coeruleus receives NTS efferents both directly and through intermediate structures such as the PBN, the nucleus paragigantocellularis (PGi), and the perifasicular area of the nucleus prepositus hypoglossi (PrH) in the rostra1 medulla (41). The latter two medullary sites send a inhibitory projection to the locus coeruleus (42,43).…”

Section: Relation To Other Brainstem Nucleimentioning

confidence: 99%

Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Walker¹,

Easton²,

Gale³

1999

Epilepsia

137

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Summary:Purpose: The nucleus of the solitary tract (NTS) is a primary site at which vagal afferents terminate. Because afferent vagal nerve stimulation has been demonstrated to have anticonvulsant effects, it is likely that changes in synaptic transmission in the NTS can regulate seizure susceptibility. We tested this hypothesis by examining the influence of y-aminobutyric acid (GABA) ergic and glutamatergic transmission in the NTS on seizures evoked by systemic and focal bicuculline and systemic pentylenetetrazol (PTZ) in rats.Methods: Muscimol (256 pmol), a GABA,-receptor agonist, bicuculline methiodide ( 1 77 pmol), a GABA,-receptor antagonist, kynurenate (634 pmol), a glutamate-receptor antagonist, or lidocaine (100 nl; 5%), a local anesthetic, was microinjected into the mediocaudal (m)NTS. Ten minutes later, seizure activity was induced by either a focal microinfusion of bicuculline methiodide ( I77 pmol) into the rostral piriform cortex, systemic PTZ (50 mg/kg, i.p.), or systemic bicuculline (0.35 mg/kg, i.v.).Results: Muscimol in mNTS (but not in adjacent regions of NTS) attenuated seizures in all seizure models tested, whereas bicuculline methiodide into mNTS did not alter seizure responses. Kynurenate infusions into mNTS significantly reduced the severity of seizures evoked both systemically and focally. Anticonvulsant effects also were obtained with lidocaine application into the same region of mNTS. Unilateral injections were sufficient to afford seizure protection.Conclusions: Our results demonstrate that an increase in GABA transmission or a decrease in glutamate transmission in the rat mNTS reduces susceptibility to limbic motor seizures. This suggests that inhibition of mNTS outputs enhances seizure resistance in the forebrain and provides a potential mechanism for the seizure protection obtained with vagal stimulation.

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Section: Relation To Other Brainstem Nucleimentioning

confidence: 99%

Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Walker¹,

Easton²,

Gale³

1999

Epilepsia

137

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“…The dendritic arbor of any individual LC neuron extends throughout and beyond the cell body region (Aston-Jones et al, 1991Ivanov and Aston-Jones, 1995;Shipley et al, 1996). Thus any individual neuron may not make extensive contacts with any other single neuron but could contact many neurons from all parts of the nucleus.…”

Section: Structure Of the Nucleusmentioning

confidence: 99%

Synchronous Activity in Locus Coeruleus Results from Dendritic Interactions in Pericoerulear Regions

1996

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Locus coeruleus (LC) neurons in brain slices from adult rats were studied using intracellular and extracellular recordings to investigate synchronous activity. Spontaneous field potentials were recorded with extracellular electrodes in solutions containing tetraethylammonium chloride (10 mM) and BaCl 2 (1 mM). These field potentials were found throughout but not outside the LC cell body region. No field potentials were observed in control solutions. Paired recordings showed that field potentials were synchronous in all areas of the LC. The synchronous activity was resistant to tetrodotoxin (1 M) and to the neurotransmitter receptor blockers D-2-amino-5-phosphonopentanoic acid, bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, idazoxan, and strychnine, suggesting that this activity was not synaptically driven. Field potentials were also synchronous with oscillations in membrane potential recorded with intracellular electrodes. The oscillations in membrane potential were 5-30 mV in amplitude and had a biphasic waveform. Neither the frequency nor the waveform of the oscillations was dependent on the membrane potential. The glycyrrhetinic acid derivative carbenoxolone and intracellular acidification with CO 2 disrupted synchronous activity, suggesting a role of electrotonic coupling. When the cell body region of the LC was isolated from the pericoerulear dendritic regions by sectioning the slice rostral and caudal to the cell body region, synchronous activity was reduced or abolished. Dendritic interaction in the pericoerulear region was also indicated by improved voltage control of the opioid-induced potassium current, as indicated by a shift in the reversal potential to the potassium equilibrium potential. The results suggest that electrical interactions between dendrites outside the cell body region can account for synchronous activity within the nucleus.

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“…Glutamate input to the LC originates predominately in the glutamatergic paragigantocellularis nucleus (Aston-Jones et al, 1986, 1991, and also from the cerebral cortex (Jodo and Aston-Jones, 1997;Jodo et al, 1998). Glutamate receptors that modulate LC activity include the N-methyl-D-aspartate receptor (NMDAR).…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

Karolewicz

Stockmeier

Ordway

2005

Neuropsychopharmacol

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Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NR1 and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher ( þ 61%, p ¼ 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum ( þ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.

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Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology

Cited by 482 publications

References 101 publications

Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Regulation of Limbic Motor Seizures by GABA and Glutamate Transmission in Nucleus Tractus Solitarius

Synchronous Activity in Locus Coeruleus Results from Dendritic Interactions in Pericoerulear Regions

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

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