Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro

Zhao, Hua; Rusak, Benjamin

doi:10.1016/j.neuroscience.2005.01.012

Cited by 141 publications

(164 citation statements)

References 81 publications

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“…For example, it was recently demonstrated that cholinergic MHb neurons corelease glutamate and ACh, but, only upon tonic photostimulation (≥20 Hz), the amount of released ACh is sufficient to activate nAChRs in postsynaptic IPN neurons (19). Interestingly, both in this study and in recordings from rat MHb neurons in vivo (29), this frequency threshold for ACh release is not reached under basal conditions. However, given the large α3β4*-dependent increase in pacemaking activity that we have observed in response to acute nicotine, it seems probable that elevation of ACh levels in the MHb as a consequence of physiological input activity or because of tobacco smoking will be important for the regulation of ACh release in the IPN.…”

Section: Discussioncontrasting

confidence: 46%

Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons

Görlich

Antolin-Fontes

Ables

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

110

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The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula-interpeduncular axis as a critical relay circuit in the control of nicotine dependence. Although clear roles for α3, β4, and α5 receptors in nicotine aversion and withdrawal have been established, the cellular and molecular mechanisms that participate in signaling nicotine use and contribute to relapse have not been identified. Here, using translating ribosome affinity purification (TRAP) profiling, electrophysiology, and behavior, we demonstrate that cholinergic neurons, but not peptidergic neurons, of the medial habenula (MHb) display spontaneous tonic firing of 2-10 Hz generated by hyperpolarization-activated cyclic nucleotidegated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist ZD7288 in the habenula precipitates somatic and affective signs of withdrawal. Further, we show that a strong, α3β4-dependent increase in firing frequency is observed in these pacemaker neurons upon acute exposure to nicotine. No change in the basal or nicotine-induced firing was observed in cholinergic MHb neurons from mice chronically treated with nicotine. We observe, however, that, during withdrawal, reexposure to nicotine doubles the frequency of pacemaking activity in these neurons. These findings demonstrate that the pacemaking mechanism of cholinergic MHb neurons controls withdrawal, suggesting that the heightened nicotine sensitivity of these neurons during withdrawal may contribute to smoking relapse.nAChRs | TRAP profiling T he tobacco epidemic kills nearly six million smokers a year, primarily from lung cancer. The success rate for smoking cessation without pharmacological treatment is only 3-5% and less than 30% with nicotine-replacement therapies (1). Nicotine, the addictive component of tobacco, mediates its action by activating nicotinic acetylcholine receptors (nAChRs), which respond to the endogenous neurotransmitter acetylcholine (ACh). Like other drugs of abuse, chronic nicotine exposure promotes adaptations in neuronal circuits that sustain the use of cigarettes (2, 3). Upon nicotine cessation in humans, a withdrawal syndrome-characterized by negative somatic and affective symptoms such as irritability, anxiety, depressed mood, and loss of concentration-develops (2, 3) and contributes to the high probability of smoking relapse. In rodents that have been chronically treated with nicotine, withdrawal can be induced either by pharmacological precipitation or by cessation of nicotine administration. Somatic and affective signs of withdrawal differentially manifest in these two cases (3, 4). Additionally, studies in knockout mice have revealed a distinct contribution of various nAChR subtypes to somatic and affective withdrawal signs (5, 6), illustrating the molecular complexity of nicotine dependence, withdrawal, and relapse.Converging evidence from genome-wide association studies...

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Section: Discussioncontrasting

confidence: 46%

Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons

Görlich

Antolin-Fontes

Ables

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

110

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“…It has been detected that there are some circadian oscillators outside the SCN, such as arcuate nucleus, paraventricular nucleus of the hypothalamus and so on (Abe, 2002). Recently, it was demonstrated that the Hb is also a member of these oscillators (Zhao, 2005;Zhao, 2015). Anatomical studies have provided the evidence that the vasopressinergic fibers from the SCN appear in the medial part of lateral habenula (LHbM) in different animals (Sofroniew, 1978), which are echoed with the results of our experiment.…”

Section: Discussionsupporting

confidence: 83%

“…Similarly, the rhythmic oscillation of Per2 expression and firing rates with higher at the day and lower at the night have also been found in the SCN neurons (Amir, 2004;Oishi, 1998;Groos, 1982;Inouye, 1979), suggesting that there may be functional connections between the SCN and the Hb. Therefore, in this experiment, the higher expression time point (13:00) during the light phase and lower expression time point of Per2 (1:00) during the dark phase based on zhao's study were selected to test the effects of SCN lesion on Per2 and c-fos mRNA expression The result in normal rats showed that there was high Per2 and c-fos mRNA level on 13:00 and low level on 1:00, which was coincident with the Zhao's (Zhao, 2015) and had similar trend with firing rates of neurons in Hb (Zhao, 2005). The characteristics of this rhythm are also consistent with that of the SCN neurons under LD condition (Harbour, 2013;Inouye, 1982;Rocha, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Some affective disorder diseases deriving from the disrupted circadian rhythms are associated with the Hb (McCathy, 2012;Yang, 2008), which has attracted many scholars' interests. Our previous experiments have manifested that there are activated and suppressed cells by the retinal illumination in the Hb and the Hb neurons also show obvious daily rhythmicity with higher baseline firing rates during the day than the night (Zhao, 2005). Moreover, recent research found that Per 2 circadian gene expression is present in the Hb both in vitro and in vivo (Guilding, 2010;Zhao, 2015).…”

Section: Introductionmentioning

confidence: 96%

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Effect of Suprachiasmatic Nucleus Lesion on Period2 and C-fos Expression in Habenular Nucleus

Xu¹,

Zhang²,

Zhao³

2015

IJC

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The habenular nucleus (Hb) located in the epithalamus is an important connection between the limbic forebrain and midbrain pathway and it regulates physiological activities including reproduction, sleep-wake, body temperature. Hb is anatomically close to the suprachiasmatic nucleus (SCN), the pacemaker of circadian rhythms in mammals. In vivo data showed circadian oscillation of Period2 (Per2) expression in Hb. However, it remains unknown whether the circadian oscillation of Per2 expression is regulated by SCN. We used semi-quantity RT-PCR methods to examine the relative expression of Per2 and c-fos mRNA in the Hb at 13:00 and 1:00 in the LD (light-dark) cycle either SCN was intact or destroyed. The expression of Per2 and c-fos mRNA in the Hb was higher at 13:00 than at 1:00. However, damaging the SCN abolished the difference of Per2 and c-fos mRNA expression at the two time ponits in the Hb, suggesting circadian oscillation of Per2 and c-fos gene in the Hb may be regulated by SCN under in vivo condition.

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“…Discriminated unit discharges were acquired and stored in 5 s bins, displayed on-line as firing-rate histograms, and stored to disk for further analysis off-line. Photically responsive neurons were identified and recorded during sustained light exposures (typically 1 min) as described previously (Zhao and Rusak, 2005). Neurons were defined as photically responsive if their firing rates were consistently increased or decreased by Ͼ30% by sustained retinal illumination.…”

Section: Methodsmentioning

confidence: 99%

Juxtacellular Recording/Labeling Analysis of Physiological and Anatomical Characteristics of Rat Intergeniculate Leaflet Neurons

Thankachan¹,

Rusak²

2005

J. Neurosci.

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The thalamic intergeniculate leaflet (IGL) is involved in mediating effects of both photic and nonphotic stimuli on mammalian circadian rhythms. IGL neurons containing neuropeptide Y (NPY) have been implicated in mediating nonphotic effects, but little is known about those involved in photic entrainment. We used juxtacellular recording/labeling in rats to characterize both photic responses and neurochemical phenotypes of neurons in the lateral geniculate area, focusing on the IGL and ventral lateral geniculate (VLG). Single neurons were recorded to characterize photic responsiveness and were labeled with Neurobiotin (Nb); tissue was stained for Nb, NPY, and in some cases for orexin A. Three classes of neurons were identified in the IGL/VLG. Type I neurons lacked NPY and showed sustained activations during retinal illumination and moderate firing rates in darkness. Type II neurons contained large amounts of NPY throughout the soma and showed varied responses to illumination: suppression, complex responses, or no response. Type III neurons had patches of NPY both on the external soma surface and within the soma, apparently representing internalization of NPY. Type III neurons resembled type I cells in their sustained activation by illumination but were virtually silent during the intervening dark period. These neurons appear to receive NPY input, presumably from other IGL cells, which may suppress their activity during darkness. These results demonstrate the presence of several classes of neurons in the IGL defined by their functional and anatomical features and reinforce the role of the IGL/VLG complex in integrating photic and nonphotic inputs to the circadian system.

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Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro

Cited by 141 publications

References 81 publications

Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons

Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons

Effect of Suprachiasmatic Nucleus Lesion on Period2 and C-fos Expression in Habenular Nucleus

Juxtacellular Recording/Labeling Analysis of Physiological and Anatomical Characteristics of Rat Intergeniculate Leaflet Neurons

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