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Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado
Submitted 29 July 2004; accepted in final form 11 February 2005
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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). The SCN is composed of numerous single-cell oscillators (i.e., "clock cells") that, when synchronized, produce a coordinated circadian output. Modification of SCN output (i.e., firing rate of SCN neurons) ultimately affects physiological and behavioral rhythms.
The SCN receives a direct glutamatergic input from the retina via the retinohypothalamic tract (RHT) that is formed from axons of retinal ganglion cells (Castel et al. 1993). In addition, the SCN receives indirect retinal input from retinorecipient neurons of the intergeniculate leaflet (IGL) via the geniculohypothalamic tract (GHT) (Morin 1994). Both of these sources of photic information modify SCN output and serve to entrain the SCN circadian clock to the 24-h environmental day-night cycle (Hendrickson et al. 1972; Moore and Lenn 1972; Pickard 1982; Pickard et al. 1987). The SCN also receives one of the densest serotonergic innervations in the brain arising from ascending projections of serotonin (5-HT) neurons in the midbrain median raphe nucleus (Meyer-Bernstein and Morin 1996). The terminal fields of retinal, IGL, and serotonergic afferents are coextensive in the ventral region of the SCN, suggesting that 5-HT afferents may modify RHT and/or IGL input to the SCN. Indeed, destruction of 5-HT afferents to the SCN modifies circadian behavioral responses to light (Morin and Blanchard 1991; Smale et al. 1990).
The 5-HT receptor subtype(s) in the SCN and their subcellular distribution remain to be fully elucidated. Of the 14 5-HT receptor subtypes currently described, several have been localized to the SCN, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT5A, and 5-HT7 receptor subtypes (Belenky and Pickard 2001; Duncan et al. 1999, 2000; Prosser et al. 1993; Rea and Pickard 2000a; Roca et al. 1993; Smith et al. 2001; Sumner et al. 1992). 5-HT1B receptors are found predominately on axon terminals within the CNS (Boschert et al. 1994). In the SCN, 5-HT1B receptors are located on RHT terminals (Belenky and Pickard 2001; Pickard et al. 1999). There is strong evidence that activation of 5-HT1B receptors in the SCN plays a particularly important role in modifying photic input (Hayashi et al. 2001; Pickard and Rea 1997; Pickard et al. 1996, 1999; Rea and Pickard 2000b; Shimazoe et al. 2004; Smith et al. 2001). However, most 5-HT1B receptors in the SCN are located on nonretinal terminals, as evidenced by the 35% reduction in the number of 5-HT1B binding sites in the SCN after bilateral enucleation (Manrique et al. 1999; Pickard et al. 1996). These nonretinal 5-HT1B receptors might be located on the terminals of other major afferents to the SCN, such as the 5-HT projection from the raphe nucleus (O’Connor and Kruk 1992) or the NPY/GABA projection from the IGL (Manrique et al. 1999). The majority of axonal boutons in the SCN are GABAergic, and they arise from the local GABAergic network, which is extensive (Castel and Morris 2000; Strecker et al. 1997; van den Pol 1986).
Recent studies with 5-HT1B receptor knockout (5-HT1B KO) mice have shown that the lack of functional 5-HT1B receptors produces an attenuated response to light (Ogilvie et al. 2004). If 5-HT1B receptors are located presynaptically on GABA terminals, the reduced response to light in KO mice may be the result of increased GABAergic neural activity in the SCN resulting from the lack of effect of 5-HT on 5-HT1B receptors. In this study, we tested the hypothesis that 5-HT inhibits GABA release in the SCN via activation of 5-HT1B presynaptic receptors on GABA terminals by analyzing the frequency and amplitude of GABAA-receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs). We examined the effects of the potent and highly selective 5-HT1B receptor agonist CP-93,129 on mIPSCs of SCN neurons in hypothalamic slices obtained from Sprague-Dawley rats and C57BL/6J wild-type and 5-HT1B KO mice.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Male Sprague-Dawley rats (Harlan) and C57BL/6J wild-type (Jackson Laboratory, Bar Harbor, ME) and 5-HT1B KO mice on the C57BL/6 background (in-house breeding and originally provided by Dr. René Hen, Columbia University) (Saudou et al. 1994) aged between 4 and 6 wk were maintained under a 12:12 light: dark cycle with lights on at 07:00 h. Food and water were available ad libitum.
Animals were deeply anesthetized by halothane inhalation and killed by decapitation at 10:00–11:00 h. Brains were then rapidly dissected, blocked in the coronal plane, and immersed in oxygenated (95% O2-5% CO2), ice-cold artificial cerebrospinal fluid (ACSF) containing (in mM) 124 NaCl, 24 NaHCO3, 3 KCl, 2 MgSO4, 1.25 NaH2PO4, 2.5 CaCl2, and 10 glucose, pH 7.4. Brain blocks were glued to the stage of a Vibratome and 300-µm-thick coronal slices containing the bilateral SCN were cut. Slices were placed in a holding chamber and incubated for 1–2 h in oxygenated ACSF at 36°C before being transferred into the recording chamber. All experiments were performed at 12:00–17:00 h.
Patch-clamp recording
Slices were continuously perfused (2 ml/min) with oxygenated ACSF (identical to that used in the dissection) and maintained at a temperature of 35°C. Pipettes were pulled (P-87 Flaming-Brown pipette puller, Sutter Instruments) from borosilicate glass capillaries of 1.65-mm OD and 0.45-mm wall thickness (Garner Glass) and filled with a solution containing (in mM) 130 CsCl, 10 N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), 1 NaCl, 1CaCl2, 1 MgCl2, 5 ethylene glycol-bis (
-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 2 ATP, 0.2 GTP, and 5 QX314, and pH adjusted to 7.2–7.3 with CsOH. Open resistance was 4–6 M
. Whole cell patch-clamp recordings were made using infrared illumination with differential interference contrast optics (IR-DIC) video microscopy. Seal resistances were typically 1–4 G, and series resistances were <20 M. After the whole cell configuration was established, cells were initially held near the resting membrane potential for 2–5 min to allow equilibration of the extracellular and recording electrode solutions. Whole cell currents were amplified with an Axopatch-Multiclamp 700A amplifier (Axon Instruments) and digitized with a Digidata 1322 (Axon Instruments). Records were collected and stored onto a Pentium III PC using the pCLAMP 8.0 software, (Axon Instruments), and analyzed off-line with Mini-Analysis software (Justin Lee, Synaptosoft). Drug effects were analyzed using the Student’s t-test. Cumulative plots were compared using the Kolmogorov-Smirnov test (KS-test; 2-tailed). The results of the cumulative plots are presented as the D value rather than using the P values. The D value is defined as the maximum value of the absolute difference between two cumulative distribution functions. Due to the large number of points in each cumulative plot, a very small difference can lead to a significant P value (i.e., <0.05), which, when combined with a small difference in the D value, can be misleading. It was therefore decided that the most appropriate way to report the results from the cumulative plots was to use the D value. All results are reported as ±SE unless stated otherwise.
Miniature IPSCs (mIPSCs) were isolated by using the glutamate AMPA/kainate receptor antagonist, 5,7-dinitroquinoxaline-2,3-dione (DNQX; 10 µM), the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV; 50 µM), and tetrodotoxin (TTX; 1 µM). Solutions of the GABAA-receptor antagonist bicuculline (30 µM) were prepared daily. DNQX and APV were obtained from RBI/Sigma (Natick, MA) and TTX was obtained from Alomone Labs. A stock solution of the highly selective 5-HT1B agonist CP-93,129 (1 mM) was prepared in water and subsequently diluted to the final concentration (1 µM, Tocris Cookson, Ellisville, MO).
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RESULTS |
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Whole cell patch-clamp recordings were obtained from 7 SCN neurons in coronal hypothalamic slices from rats and 12 SCN neurons from mice (only 1 cell was recorded from each slice). Cells were voltage-clamped at –60 mV. Resting membrane potentials could not be measured due to the pipette recording solution containing CsCl and QX314. However, after establishing the whole cell configuration, a period of 2–5 min was allowed for the equilibration of intracellular and recording solutions before recording began. In all recordings, a stable baseline was achieved, and then the drug was applied followed by a washout period of 
20 min or for as long as the recording was adequate. GABAA-receptor-mediated mPSCs were pharmacologically isolated by applying a combination of APV (50 µM) and DNQX (10 µM) to block NMDA and AMPA/kainate receptors, respectively, and TTX (1 µM) to block sodium-mediated action potentials and the postsynaptic currents from them. All remaining currents could be reversibly suppressed by the GABAA receptor antagonist bicuculline (30 µM), shown in Fig. 1. Due to the high variance in both the frequency and amplitude of mIPSCs between individual cells, effects were best assessed as a percentage of control values. In experiments using mice, the investigator was blind concerning the genotype (i.e., wild-type vs. 5-HT1B KO).
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CP-93,129 (1 µM) was bath applied, and the slices (n = 7) were exposed to the 5-HT1B agonist for 4 min (Fig. 2). Data from dose-dependent responses for CP-93,129 indicate 1 µM to be a maximally effective dose (e.g., Berger and Huynh 2002). In three of the cells tested, mIPSCs showed a decrease in frequency; before exposure to CP-93,129, the average frequency of mIPSCs for these three cells was 3.0 ± 2.0 Hz compared with 1.3 ± 0.6 Hz after exposure to the 5-HT1B agonist (i.e., a 57% reduction). The mIPSC amplitude was reduced from 49.2 ± 10.0 pA in the control period to 41.4 ± 5.9 pA (i.e., 16%) after application of the agonist. The cumulative plot (Fig. 3C) of mIPSC amplitude from a representative cell within this group gives a D value of 0.1, representing a maximal 10% shift between the two data plots at one point. This indicates a relatively small decrease in mIPSC amplitude, and the KS test showed that this was not significantly different (i.e., P = 0.1). Unlike the effect on frequency, this small effect on amplitude did not recover, suggesting that it was due to slight deterioration of the recording rather than an effect of the agonist. Of the three cells that showed the decrease in frequency in response to CP-93,129, the mIPSC frequency of two cells recovered completely to control levels in the washout period, and one recording was lost before complete washout was achieved. The remaining four cells of the seven tested showed no clear change in frequency (7.0 ± 5.2 Hz baseline compared with 6.3 ± 4.7 Hz with 5-HT1B agonist) or amplitude (45.1 ± 2.1 pA compared with 42.4 ± 2.1 pA) of mIPSCs in response to CP-93,129 application. If we consider all seven cells tested as a single population, then a conservative calculation is that CP-93,129 caused a 22% reduction in the frequency of mIPSCs (P = 0.03, paired t-test), and this is summarized in Fig. 8A. That the effect of CP-93,129 was predominately if not exclusively on the frequency of mIPSCs suggests a presynaptic action of the 5-HT1B receptor agonist.
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The same experimental procedure as used for the rat was followed for the mouse. CP-93,129 (1 µM) was bath applied, and cells were exposed to the 5-HT1B agonist for 4 min. In slices prepared from wild-type mice, the effect of CP-93,129 was tested on eight cells. Of the eight cells tested, three showed a large reduction in mIPSC frequency in response to CP-93,129 application. In the control period, the frequency of mIPSCs was 2.3 ± 0.5 Hz compared with 1.1 ± 0.4 Hz during drug exposure, reflecting a 52% reduction. A representative recording from a cell within this group is shown in Fig. 4. An additional three cells showed a more subtle but still clear effect of CP-93,129. In these cells, the frequency of mIPSCs in the control period was 4.8 ± 2.6 Hz and was 3.7 ± 2.1 Hz during drug application, a 23% reduction in frequency. The frequency of mIPSCs did not fully recover to control levels in those cells that showed a more dramatic response to CP-93,129, but there was a definite trend of increasing mIPSC frequency during the washout period. The remaining two cells did not show a clear effect in response to CP-93,129. The cumulative plots of the eight cells show D values in the range of 0.02 (2%) and 0.18 (18%), and the cumulative plot for the representative recording from wild-type mice is shown in Fig. 5C. However, the amplitude changes were not consistent: in five cells the amplitude of mIPSCs was slightly smaller after the application of CP-93,129, but the amplitudes were larger in the remaining three cells. Overall, the amplitude was 31.1 ± 6.2 pA in the control period compared with 32.9 ± 6.8 pA during exposure to the 5-HT1B receptor agonist. In the eight cells tested, CP-93,129 decreased the frequency (but not the amplitude) of mIPSCs by an overall average of 30% (P = 0.01, paired t-test), as summarized in Fig. 8B.
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There was a negligible effect of CP-93,129 application when tested on slices from four 5-HT1B KO animals; one cell was recorded from each animal. In the control period, the frequency of mIPSCs was 2.5 ± 0.5 Hz and the amplitude was 17.8 ± 4.1 pA compared with 2.4 ± 0.5 Hz and 14 ± 3.6 pA during drug exposure. A representative recording of an SCN neuron from a 5-HT1B KO mouse is shown in Fig. 6, and data for all four cells are summarized in Fig. 8C; the change in amplitude was not found to be significant (P = 0.2). The D values from the cumulative plots ranged from 0.1 to 0.2 (Fig. 7), and as with the wild-type mice, the change in mIPSC amplitude was not consistently in one direction (i.e., 50% of the cells showed a small increase in mIPSC amplitude after exposure to CP-93,129 and 2 cells showed a decrease in amplitude. The effect of CP-93,129 on the frequency of mIPSCs in six of eight cells from wild-type mice was significantly different from the response to CP-93,129 on the frequency of mIPSCs in cells from 5-HT1B KO mice (0 of 4 cells; P = 0.03, Fisher’s exact test, 1-tailed).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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) reduced the frequency but not the amplitude of GABAergic mIPSCs in the majority of cells tested from animals with functional 5-HT1B receptors, indicating a presynaptic site of action. This finding is consistent with the location of this receptor in the CNS predominately on axon terminals (Boschert et al. 1994) and numerous reports demonstrating 5-HT1B receptor-mediated presynaptic inhibition of transmitter release in several different regions of the CNS (Berger and Huynh 2002; Mlinar et al. 2003; Mooney et al. 1994; Pickard et al. 1999; Singer et al. 1996; Smith et al. 2001; Stanford and Lacey 1996; Tanaka and North 1993).
The location of the cell bodies that give rise to the GABAergic axon terminals examined in this study is not known with certainty. GABA terminals in the SCN are known to arise from several sources, including GABAergic neurons in the IGL that project to the SCN via the GHT (Morin 1994). However, most GABAergic axonal boutons in the SCN originate from the extensive GABAergic local network in the SCN (Castel and Morris 2000; Strecker et al. 1997; van den Pol 1986). 5-HT1B mRNA has been reported in the SCN (Roca et al. 1993), consistent with a local site of receptor synthesis. Manrique and colleagues (1999) have provided indirect evidence for 5-HT1B binding sites associated with GHT terminals in the SCN. It may well be the case that not all GABAergic terminals within the SCN express the 5HT1B receptor. This would explain the lack of effect of CP-93,129 on some of the cells recorded, and because we were not able to determine the source of the GABAergic terminals in these experiments, it is difficult to separate the cells into different groups without additional characterization of the recorded cells. Experiments using procedures similar to those described in the current study conducted in animals in which the IGL has been ablated may help to resolve this issue.
Although the polar character of CP-93,129 is apparently the reason, it has very low penetrability into the CNS, it is also probably responsible for its selective affinity at 5-HT1B receptors (Koe et al. 1992b). Indeed, at a concentration (1 µM) shown to be maximally effective at inhibiting transmitter release in vitro in previous studies (Berger and Huynh 2002; Mlinar et al. 2003; Singer et al. 1996), CP-93,129 was ineffective in altering the frequency of mIPSCs in mice lacking functional 5-HT1B receptors. The variability in mIPSC frequency between successive 120-s bins during the baseline period in all recordings was 
8.9 ± 1.1%, so the change of 
7% that was seen in KO animals is within the inherent variability in the system; therefore CP-93,129 showed negligible effects in the 5-HT1B KO mice. The mIPSC amplitude also varied (6.4 ± 1.3%) between successive 120-s bins during the baseline period. We have shown in previous studies that 5-HT1B KO mice serve as excellent pharmacological controls for examining the specificity of 5-HT1B receptor agonists both in vivo and in vitro (Pickard et al. 1999; Smith et al. 2001). Taken together, these data support the interpretation that the response of the 5-HT1B agonist used in rats and wild-type mice was due to the activation of 5-HT1B receptors (Fig. 8).
Previous work has shown that 5-HT1B receptors on retinal terminals act to inhibit the response of SCN neurons to light stimulation (Pickard et al. 1999; Smith et al. 2001). Thus one might expect that in the 5-HT1B KO mouse there would be an enhanced response of the circadian system to light stimulation. However, this is apparently not the case, as behavioral studies indicate that 5-HT1B KO animals actually exhibit an attenuated response to photic stimulation (Ogilvie et al. 2004). The relative number of GABA terminals in the SCN far outweighs the number of glutamatergic retinal terminals in the SCN, so even with the removal of 5-HT1B inhibition on glutamate release from the retinal terminals, the lack of inhibition of GABA release may have a much greater total effect with an outcome of an attenuated response to light stimulation. It is not understood at present how increased SCN GABA release in 5-HT1B KO mice may alter the response of the SCN circadian system to light. It is possible that excessive GABA release activates GABAB receptors that are located on RHT terminals (Jiang et al. 1995). Additional work is clearly necessary to reveal the underlying physiological mechanisms responsible for the attenuated response of 5-HT1B KO animals to light.
The relationship between 5-HT and GABA terminals in the SCN has long been recognized. Bosler (1989) described extensive axo-axonal interactions between 5-HT and GABA terminals in the SCN and suggested that "every 5-HT varicosity in the SCN might well be apposed to at least one GABA terminal." Indirect evidence from circadian behavioral studies (Mintz et al. 1997) and 5-HT-induced Ca+2 transients in the SCN (Flett and Colwell 1999) suggests that 5-HT can act within the SCN to alter GABA activity. Jiang and colleagues (2000) provide evidence from SCN neurons in hypothalamic slices that 5-HT can alter GABA release via a presynaptic mechanism (in 3 of 10 cells); although the 5-HT receptor subtype mediating this response was not specified. 5-HT7 receptors have been described on GABA terminals in the SCN (Belenky and Pickard 2001) and the current study also supports the localization of 5-HT1B receptors on GABA terminals in the SCN. Indeed, the presynaptic interactions between 5-HT and GABA may well be wide spread throughout the CNS (Belenky and Pickard 2001; Johnson et al. 1992; Matsuoka et al. 2004; Stanford and Lacey 1996; van Bockstaele et al. 1996; Yan and Yan 2001).
In summary, the present study provides data from SCN neurons in hypothalamic slices from rat and mouse indicating that 5-HT1B receptors are located presynaptically on GABA axonal terminals and that activation of these receptors inhibits GABA release.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: G. E. Pickard, Dept. of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, CO 80523 (E-mail: gary.pickard{at}colostate.edu)
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Berger AJ and Huynh P. Activation of 5-HT1B receptors inhibits glycinergic synaptic inputs to mammalian motoneurons during postnatal development. Brain Res 956: 380–384, 2002.[CrossRef][ISI][Medline]
Boschert U, Amara DA, Segu L, and Hen R. The mouse 5-hydoxytryptamine1B receptor is localized predominately on axon terminals. Neuroscience 58: 167–182, 1994.[CrossRef][ISI][Medline]
Bosler O. Ultrastructural relationships of serotonin and GABA terminals in the rat suprachiasmatic nucleus. Evidence for a close interconnection between the two afferent systems. J Neurocytol 18: 105–113, 1989.[CrossRef][ISI][Medline]
Castel M, Belenky M, Cohen S, Ottersen OP, and Storm-Mathisen J. Glutamate-like immunoreactivity in retinal terminals of the mouse suprachiasmatic nucleus. Eur J Neurosci 5: 368–381, 1993.[CrossRef][ISI][Medline]
Castel M and Morris JF. Morphological heterogeneity of the GABAergic network in the suprachiasmatic nucleus, the brain’s circadian pacemaker. J Anat 196: 1–13, 2000.[Medline]
Duncan MJ, Jennes L, Jefferson JB, and Brownfield MS. Localization of serotonin5A receptors in discrete regions of the circadian timing system in the Syrian hamster. Brain Res 869: 178–185, 2000.[CrossRef][ISI][Medline]
Duncan MJ, Short J, and Wheeler DL. Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters. Brain Res 829: 39–45, 1999.[CrossRef][ISI][Medline]
Flett J and Colwell CS. Serotonin modulation of calcium transients in cells in the suprachiasmatic nucleus. J Biol Rhythms 14: 354–363, 1999.[Abstract]
Hayashi S, Ueda M, Amaya F, Matusda T, Tamada Y, Ibata Y, and Tanaka M. Serotonin modulates expression of VIP and GRP mRNA via the 5HT1B receptor in the suprachiasmatic nucleus of the rat. Expl Neurol 171: 285–292, 2001.
Hendrickson AE, Wagoner N, and Cowan WM. An autoradiographic and electron microscope study of retinohypothalamic connections. Z Zellforsch 135: 1–26, 1972.[CrossRef][ISI][Medline]
Jiang ZG, Allen CN, and North RA. Presynaptic inhibition by baclofen of retinohypothalamic excitatory synaptic transmission in rat suprachiasmatic nucleus. Neuroscience 64: 813–819, 1995.[CrossRef][ISI][Medline]
Jiang ZG, Teshima K, Yang YQ, Yoshioka T, and Allen CN. Pre- and postsynaptic actions of serotonin on rat suprachiasmatic nucleus neurons. Brain Res 866: 247–256, 2000.[CrossRef][ISI][Medline]
Johnson SW, Mercuri NB, and North RA. 5-Hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons. J Neurosci 12: 2000–2006, 1992.[Abstract]
Klein DC, Moore, RY, and Reppert SM. Suprachiasmatic nucleus. In: The Mind’s Clock, Oxford, New York, 1991, p. 4–16.
Koe BK, Lebel LA, Fox CB, and Macor JE. Binding and uptake studies with [3H]CP-93,129, a radiolabeled selective 5-HT1B receptor ligand. Drug Dev Res 25: 67–74, 1992a.
Koe BK, Nielsen JA, Macor JE, and Heym J. Biochemical and behavioral studies of the 5-HT1B receptor agonist, CP-94,253. Drug Dev Res 26: 241–250, 1992b.[CrossRef][ISI]
Manrique C, Hery F, Faudon M, and Francois-Bellan AM. Indirect evidence for an association of 5-HT1B binding sites with retinal and geniculate axon terminals in the rat suprachiasmatic nucleus. Synapse 33: 314–323, 1999.[CrossRef][ISI][Medline]
Matsuoka T, Hasuo H, and Akasu T. 5-Hydroxytryptamine1B receptors mediate presynaptic inhibition of monosynaptic IPSC in the rat dorsolateral septal nucleus. Neurosci Res 48: 229–238, 2004.[CrossRef][ISI][Medline]
Meyer-Bernstein EL and Morin LP. Differential seroternergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J Neurosci 16: 2097–2111, 1996.
Mintz EM, Gillespie CF, Marvel CL, Huhman KL, and Albers HE. Serotonergic regulation of circadian rhythms in Syrian hamsters. Neuroscience 79: 563–569, 1997.[CrossRef][ISI][Medline]
Mlinar B, Falsini C, and Corradetti R. Phamacological characterization of 5-HT1B receptor-mediated inhibition of local excitatory synaptic transmission in the CA1 region of rat hippocampus. Br J Pharmacol 138: 71–80, 2003.[CrossRef][ISI][Medline]
Mooney RD, Shi MY, and Rhoades RW. Modulation of retinotectal transmission by presynaptic 5-HT1B receptors in the superior colliculus of the adult hamster. J Neurophysiol 72: 3–13, 1994.
Moore RY and Lenn NJ. A retinohypothalamic projection in the rat. J Comp Neurol 146: 1–14, 1972.[CrossRef][ISI][Medline]
Morin LP. The circadian visual system. Brain Res Rev 67: 102–127, 1994.
Morin LP and Blanchard J. Depletion of brain serotonin by 5,7-DHT modifies hamster circadian rhythm response to light. Brain Res 566: 173–185, 1991.[CrossRef][ISI][Medline]
O’Connor JJ and Kruk ZL. Pharmacological characteristics of 5-hydroxytryptamine autoreceptors in rat brain slices incorporating the dorsal raphe or the suprachiasmatic nucleus. Br J Pharmacol 106: 524–532, 1992.[ISI][Medline]
Ogilvie MD, Sollars PJ, and Pickard GE. Attenuated response to light in the 5HT1B receptor knockout mouse results in phase delayed entrainment to winter-like photoperiods. SRBR 9:174, 2004.
Pickard GE. The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection. J Comp Neurol 211: 65–83, 1982.[CrossRef][ISI][Medline]
Pickard GE, Ralph MR, and Menaker M. The intergeniculate leaflet partially mediates effects of light on circadian rhythms. J Biol Rhythms 2: 35–56, 1987.
Pickard GE and Rea MA. Serotonergic innervation of the hypothalamic suprachiasmatic nucleus and photic regulation of circadian rhythms. Biol Cell 89: 513–523, 1997.[CrossRef][ISI][Medline]
Pickard GE, Smith BN, Belenky M, Rea MA, Dudek FE, and Sollars PJ. 5HT1B receptor-mediated presynaptic inhibition of retinal input to the suprachiasmatic nucleus. J Neurosci 19: 4034–4045, 1999.
Pickard GE, Weber TE, Scott PA, Riberdy AF, and Rea MA. 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. J Neurosci 16: 8208–8220, 1996.
Prosser RA, Dean RR, Edgar DM, Heller HC, and Miller JD. Serotonin and the mammalian circadian system. I. In vitro phase shifts by serotonergic agonists and antagonists. J Biol Rhythms 8: 1–16, 1993.
Rea MA and Pickard GE. Serotonergic modulation of photic entrainment in the Syrian hamster. Biol Rhythm Res 31: 284–314, 2000a.[CrossRef]
Rea MA and Pickard GE. A 5HT1B receptor agonist inhibits light-induced suppression of pineal melatonin. Brain Res 858: 424–428, 2000b.[CrossRef][ISI][Medline]
Roca AL, Weaver DR, and Reppert SM. Serotonin receptor gene expression in the rat suprachiasmatic nuclei. Brain Res 608: 159–165, 1993.[CrossRef][ISI][Medline]
Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L, Buhot MC, and Hen R. Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265: 1875–1878, 1994.
Shimazoe T, Nakamure S, Kobayashi K, Watanabe S, Miyasaka K, Kono A, and Funakoshi A. Role of 5-HT1B receptors in entrainment disorder of otsuka long evans tokushima fatty (OLETF) rats. Neuroscience 123: 201–205, 2004.[CrossRef][ISI][Medline]
Singer JH, Bellingham MC, and Berger AJ. Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons by serotonin. J Neurophysiol 76: 799–807, 1996.
Smale L, Michels KM, Moore RY, and Morin LP. Destruction of the hamster serotonergic system by 5,7-DHT: effects on circadian rhythm phase, entrainment and response to triazolam. Brain Res 515: 9–19, 1990.[CrossRef][ISI][Medline]
Smith BN, Sollars PJ, Dudek FE, and Pickard GE. Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5HT1B and 5HT7 receptors. J Biol Rhythms 16: 25–38, 2001.[Abstract]
Stanford IM and Lacey MG. Differential actions of serotonin, mediated by 5-HT1B and 5-HT2C receptors on GABA-mediated synaptic input to rat substantia nigra pars reticulate neurons in vitro. J Neurosci 16: 7566–7573, 1996.
Strecker GJ, Wuarin J-P, and Dudek FE. GABAA-mediated local synaptic pathways connect neurons in the rat suprachiasmatic nucleus. J Neurophysiol 78: 2217–2220, 1997.
Sumner BEH, Rosie R, and Fink G. Relative density of 5-hydroxytryptamine receptor subtype mRNAs in female rat neuroendocrine brain determined by in situ hybridization histochemistry. Mol Cell Neurosci 3: 215–223, 1992.[CrossRef]
Tanaka E and North RA. Actions of 5-Hydroxytryptamine on neurons of the rat cingulate cortex. J Neurophysiol 69: 1749–1757, 1993.
Van Bockstaele EJ, Chan J, and Pickel VM. Pre- and postsynaptic sites for serotonin modulation of GABA-containing neurons in the shell region of the rat nucleus accumbens. J Comp Neurol 370: 116–128, 1996.
van den Pol AN. Gamma-aminobutyrate, gastrin releasing peptide, serotonin, somatostatin, and vasopressin: ultrastructural immunocytochemical localization in presynaptic axons in the suprachiasmatic nucleus. Neuroscience 17: 643–659, 1986.[CrossRef][ISI][Medline]
Yan QS and Yan SE. Serotonin-1B receptor-mediated inhibition of [3H]GABA release from ventral tegmental area slices. J Neurochem 79: 914–922, 2001.[CrossRef][ISI][Medline]
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