Noradrenergic lesion of the locus coeruleus increases the firing activity of the medial prefrontal cortex pyramidal neurons and the role of α2-adrenoceptors in normal and medial forebrain bundle lesioned rats

Wang, Yong; Zhang, Qiao Jun; Liu, Jian; Ali, Umar; Gui, Zhen; Hui, Yan Ping; Wang, Tao; Chen, Li; Li, Qiang

doi:10.1016/j.brainres.2010.02.009

Cited by 20 publications

(17 citation statements)

References 55 publications

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“…In addition, NA seems to be involved also in modulating the activity of other types of neurons, such as SN pars reticulata neurons and cortical pyramidal neurons. For instance, bilateral lesions of LC NA neurons with 6-OHDA in DA lesioned rats increased the firing activity of SN pars reticulata neurons (Wang et al, 2010a) and medial prefrontal cortex pyramidal neurons (Wang et al, 2010b). In addition, firing rate of serotonin neurons (Haddjeri et al, 1996;Vandermaelen and Aghajanian, 1983;Svensson et al, 1975) and serotonin synthesis and release (Adell and Artigas, 1999;Pudovkina et al, 2002Pudovkina et al, , 2003Amargos-Bosch et al, 2003;Mongeau et al, 1997;Yoshioka et al, 1992) has been shown to be modified by NA input.…”

Section: Discussionmentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, studies of post-mortem PD brains have shown that not only DA neurons but also the noradrenergic (NA) neurons in the locus coeruleus degenerate, and that the NA neurodegeneration may be as profound, and also precede degeneration of the midbrain DA neurons. Previous studies in animal models of PD have suggested that loss of forebrain NA will add to the development of motor symptoms in animals with lesions of the nigrostriatal DA neurons, but the results obtained in rodents have been inconclusive due to the shortcomings of the toxin, DSP-4, used to lesion the NA projections. Here, we have developed an alternative double-lesion paradigm using injections of 6-OHDA into striatum in combination with intraventricular injections of a powerful NA immunotoxin, anti-DBH-Saporin, to eliminate the NA neurons in the brain.Animals with combined DA and NA lesions were more prone to develop L-DOPAinduced dyskinesia, even at low L-DOPA doses, and they performed significantly worse in tests of reflexive and skilled paw use, the stepping and staircase tests, compared to DA-only lesioned rats. Post-mortem analysis revealed that NA depletion did not affect the degree of DA depletion, or the loss of tyrosine hydroxylase-positive innervation in the striatum. Cell loss in the substantia nigra was similar in both single and double lesioned animals, showing that the worsening effect was not due to increased loss of nigral DA neurons. The results show that damage to the NA neurons in the central nervous system contributes to the development of motor impairments and the appearance of L-DOPAinduced dyskinesia in 6-OHDA lesioned rats, and provide support for the view that the development of motor symptoms and dyskinetic side effects in PD patients reflects the combined loss of midbrain DA neurons and NA neurons.3

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Section: Discussionmentioning

confidence: 99%

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Shin

Rogers

Devoto

et al. 2014

Experimental Neurology

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“…Similarly, while the numbers of cells in the GFP-positive and GFP-negative groups in the electrophysiology study are relatively low, the data appear robust with relatively low variability across the cells in each experimental group. However, an unresolved interpretation issue in the electrophysiology experiment is whether yohimbine-induced synaptic alterations in mPFC activated neurons are due to the drug’s effect on the motivation to seek food or are due to the unconditioned pharmacological effects of yohimbine, which include stimulation of pyramidal cell firing (Wang et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Medial Prefrontal Cortex Neuronal Activation and Synaptic Alterations after Stress-Induced Reinstatement of Palatable Food Seeking: A Study Using c-fos-GFP Transgenic Female Rats

Cifani

Koya

Navarre

et al. 2012

Journal of Neuroscience

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Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express green fluorescent protein (GFP) in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5–2 mg/kg) or pellet priming (1–4 non-contingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and non-activated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPAR/NMDAR current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. Together, while ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.

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“…Ample evidence exists that α 2 Rs directly modulate PFC activity (Kovács and Hernádi, 2003; Wang et al, 2010), reviewed in Arnsten and Li (2005). Most of this literature indicates a beneficial effect of α 2 R activation for working memory, although in some studies beneficial effects of α 2 R blockers have been described (Brown et al, 2012; Bari and Robbins, 2013).…”

Section: α2rs Central Modulationmentioning

confidence: 99%

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

Atzori

Cuevas-Olguín

Esquivel-Rendón

et al. 2016

Front. Synaptic Neurosci.

113

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Norepinephrine (NE) is synthesized in the Locus Coeruleus (LC) of the brainstem, from where it is released by axonal varicosities throughout the brain via volume transmission. A wealth of data from clinics and from animal models indicates that this catecholamine coordinates the activity of the central nervous system (CNS) and of the whole organism by modulating cell function in a vast number of brain areas in a coordinated manner. The ubiquity of NE receptors, the daunting number of cerebral areas regulated by the catecholamine, as well as the variety of cellular effects and of their timescales have contributed so far to defeat the attempts to integrate central adrenergic function into a unitary and coherent framework. Since three main families of NE receptors are represented—in order of decreasing affinity for the catecholamine—by: α2 adrenoceptors (α2Rs, high affinity), α1 adrenoceptors (α1Rs, intermediate affinity), and β adrenoceptors (βRs, low affinity), on a pharmacological basis, and on the ground of recent studies on cellular and systemic central noradrenergic effects, we propose that an increase in LC tonic activity promotes the emergence of four global states covering the whole spectrum of brain activation: (1) sleep: virtual absence of NE, (2) quiet wake: activation of α2Rs, (3) active wake/physiological stress: activation of α2- and α1-Rs, (4) distress: activation of α2-, α1-, and β-Rs. We postulate that excess intensity and/or duration of states (3) and (4) may lead to maladaptive plasticity, causing—in turn—a variety of neuropsychiatric illnesses including depression, schizophrenic psychoses, anxiety disorders, and attention deficit. The interplay between tonic and phasic LC activity identified in the LC in relationship with behavioral response is of critical importance in defining the short- and long-term biological mechanisms associated with the basic states postulated for the CNS. While the model has the potential to explain a large number of experimental and clinical findings, a major challenge will be to adapt this hypothesis to integrate the role of other neurotransmitters released during stress in a centralized fashion, like serotonin, acetylcholine, and histamine, as well as those released in a non-centralized fashion, like purines and cytokines.

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Noradrenergic lesion of the locus coeruleus increases the firing activity of the medial prefrontal cortex pyramidal neurons and the role of α2-adrenoceptors in normal and medial forebrain bundle lesioned rats

Cited by 20 publications

References 55 publications

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Noradrenaline neuron degeneration contributes to motor impairments and development of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease

Medial Prefrontal Cortex Neuronal Activation and Synaptic Alterations after Stress-Induced Reinstatement of Palatable Food Seeking: A Study Using c-fos-GFP Transgenic Female Rats

Locus Ceruleus Norepinephrine Release: A Central Regulator of CNS Spatio-Temporal Activation?

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