Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms
NeuronPublished 1 April 1995Open access
David K. Welsh, Diomedes E. Logothetis, Markus Meister, Steven M. Reppert
Citations1,451
SJR quartileQ1
SJR score6.75
SNIP2.95
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is suggested that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them.
Abstract
Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses, circadian rhythms expressed by neurons in the same culture are not synchronized. After reversible blockade of neuronal firing lasting 2.5 days, circadian firing rhythms re-emerge with unaltered phases. These data suggest that the SCN contains a large population of autonomous, single-cell circadian oscillators, and that synapses formed in vitro are neither necessary for operation of these oscillators nor sufficient for synchronizing them.
Keywords
PsychologyNeuroscience
Biophysical JournalNeuronal Spike Trains and Stochastic Point Processes
1,499 Citations1967Donald H. Perkel, George L. Gerstein +1 more
The statistical techniques available for the analysis of single spike trains are described and related to the underlying mathematical theory, that of stochastic point processes, whose realizations may be described as series of point events occurring in time, separated by random intervals.
Biophysical JournalNeuronal Spike Trains and Stochastic Point Processes
1,317 Citations1967Donald H. Perkel, George L. Gerstein +1 more
The statistical analysis of two simultaneously observed trains of neuronal spikes is described, using as a conceptual framework the theory of stochastic point processes, and the theory presented is illustrated by an application to experimentally obtained data from auditory neurons.
Culturing nerve cells
1,290 Citations1998Gary Banker, Kimberly Goslin
A user's guide to types of nerve cell cultures, their advantages and limitations, and tissue culture methods for the study of myelination.
ScienceSynchronous Bursts of Action Potentials in Ganglion Cells of the Developing Mammalian Retina
1,129 Citations1991Markus Meister, Rachel Wong +2 more
The development of orderly connections in the mammalian visual system depends on action potentials in the optic nerve fibers, even before the retina receives visual input, and correlated firing of retinal ganglion cells in the same eye directs the segregation of their synaptic terminals into eye-specific layers within the lateral geniculate nucleus.
NeuronCloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses
1,100 Citations1994Steven M. Reppert, David R. Weaver +1 more
The cloning and characterization of a high affinity receptor for melatonin from the sheep and human is reported, likely mediates the reproductive and circadian actions of melatonin in mammals.
Journal of Theoretical BiologyThe chi square periodogram: Its utility for analysis of circadian rhythms
991 Citations1978Phillip G. Sokolove, Wayne N. Bushell
It is shown that even for relatively short (10 day) time series, the integral-valued chi-square periodogram can distinguish circadian-periodic from random series at a level of significance of about 0·01.
Proceedings of the National Academy of SciencesPersistence of circadian rhythmicity in a mammalian hypothalamic "island" containing the suprachiasmatic nucleus.
984 Citations1979Sachiye Inouye, Hiroshi Kawamura
Simultaneous recording from two extracellular electrodes indicated neural activity at two sites in the brain, one of which is in or near the suprachiasmatic nucleus and the other in one of many other brain locations, which indicated clear circadian rhythmicity of spontaneous neural activity.
Physiological ReviewsNeurophysiology of the suprachiasmatic circadian pacemaker in rodents
736 Citations1989Johanna H. Meijer, W.J. Rietveld
The Journal of Cell BiologyIdentification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells.
722 Citations1985Kathleen M. Buckley, R B Kelly
A transmembrane glycoprotein (Mr approximately 100,000) is described that is present in secretory vesicles in all neurons and endocrine cells studied, in species from elasmobranch fish to mammals, and in neural andendocrine cell lines.
The Journal of Comparative NeurologyGABA: A dominant neurotransmitter in the hypothalamus
571 Citations1990Chantal Decavel, Anthony N. van den Pol
It is suggested that GABA is the numerically dominant neurotransmitter in the hypothalamus, and the importance of inhibitory circuits in theothalamus is emphasized.
NeuronTransient period of correlated bursting activity during development of the mammalian retina
566 Citations1993Rachel Wong, Markus Meister +1 more
It is shown that the spontaneous activity of cells in the neonatal ferret retina is correlated by patterns of periodically generated traveling waves and that retinal ganglion cells participate in these patterns of activity, which are seen during the same period as synaptic modification in the lateral geniculate nucleus.
ScienceResetting the Biological Clock: Mediation of Nocturnal Circadian Shifts by Glutamate and NO
566 Citations1994Jian Ding, Chen Dong +4 more
Data indicate that Glu release, NMDA receptor activation, NOS stimulation, and NO production link light activation of the retina to cellular changes within the SCN mediating the phase resetting of the biological clock.
Journal of Neuroscience MethodsRecording action potentials from cultured neurons with extracellular microcircuit electrodes
551 Citations1980Jerome Pine
Dissociated cell cultures of neurons from neonatal rat superior cervical ganglia have been grown in specially prepared dishes, the bottoms of which consist of glass coverslips on which thin-film microcircuits have been deposited, suitable for passing the current required for extracellular stimulation.
Neuroscience LettersGABA is the principal neurotransmitter of the circadian system
549 Citations1993Robert Y. Moore, Joan C. Speh
It is demonstrated that neurons of both nuclei colocalize GABA with peptides in the IGL and SCN, and GABA should be considered the principal neurotransmitter of the circadian system.
NeuroscienceNeurotransmitters of the hypothalamic suprachiasmatic nucleus: Immunocytochemical analysis of 25 neuronal antigens
532 Citations1985Anthony N. van den Pol, Kengo Tsujimoto
An immunocytochemical analysis with 33 antisera was undertaken to investigate the localization of 25 different neurotransmitter-related antigens in the hypothalamic suprachiasmatic nucleus in the rat, suggesting that dopamine, norepinephrine and epinephrine may occur in a limited number of axons in the nucleus.
The Journal of Comparative NeurologyEfferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat
505 Citations1987Alan G. Watts, Larry W. Swanson
The PHA‐L method was used to show that the subparaventricular zone projects in turn massively to these same regions, as well as back to the SCh itself and to the periaqueductal gray.
Brain ResearchCircadian rhythm of firing rate recorded from single cells in the rat suprachiasmatic brain slice
502 Citations1982Daniel J. Green, Rhanor Gillette
Brain slices, containing the suprachiasmatic nuclei, of rats were removed at various times of the fay and the firing rates of single cells were recorded and found to maintain a circadian rhythm in temporal accord with the light/dark cycle of the donor animal.
Journal of Neuroscience MethodsMulti-neuronal signals from the retina: acquisition and analysis
415 Citations1994Markus Meister, Jerome Pine +1 more
A new method for monitoring the simultaneous electrical activity of many neurons in a functioning piece of retina and a method of visual stimulation and data analysis that allows a rapid characterization of each neuron's visual response properties are presented.
Neuroscience LettersCircadian rhythms in electrical discharge of rat suprachiasmatic neurones recorded in vitro
324 Citations1982G. A. Groos, Jan Hendriks
The SCN explant is capable of endogenous generation of at least one circadian cycle in vitro and exhibited a circadian rhythm similar to that reported for the SCN in freely moving animals.
Journal of NeuroscienceNeurophysin in the hypothalamo-neurohypophysial system. I. Production and characterization of monoclonal antibodies
320 Citations1985Y Ben-Barak, J. T. Russell +3 more
Solid phase specificities and absorption controls of antibodies are demonstrated to be inadequate to assess their immunocytochemical (solid phase) specificities, demonstrating heterogeneity of NP-AVP and NP-OT in the rat posterior pituitary.
Brain ResearchMelatonin directly resets the rat suprachiasmatic circadian clock in vitro
314 Citations1991Angela J. McArthur, Martha U. Gillette +1 more
Melatonin can directly reset this circadian clock during the period surrounding the day-night transition, and is tested in a rat brain slice preparation maintained in vitro for 2-3 days.
Neuroscience LettersA new fixed-array multi-microelectrode system designed for long-term monitoring of extracellular single unit neuronal activity in vitro
297 Citations1977Guenter W. Gross, E. Rieske +2 more
This two-dimensional system can be used as the floor of a tissue culture chamber and should be suitable for simultaneous long-term monitoring of single unit extracellular electrical activity from more than 30 neurons in culture.
Brain ResearchCircadian rhythmic changes of neuronal activity in the suprachiasmatic nucleus of the rat hypothalamic slice
279 Citations1982Shigenobu Shibata, Yutaka Oomura +2 more
The Journal of Comparative NeurologyCentral somatostatin systems revealed with monoclonal antibodies
269 Citations1985S.R. Vincent, C. H. S. McIntosh +2 more
A large number of positive cell groups including many previously undescribed populations were detected throughout the brain and spinal cord, suggesting a pallidohabenula somatostatin pathway.
Annual Review of PhysiologyOscillatory Neural Networks
266 Citations1985Allen I. Selverston, Maurice Moulins
The real question remains: Can a group of cells produce an oscillatory pattern without phasic sensory input?
Proceedings of the National Academy of SciencesThe suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker.
260 Citations1987William J. Schwartz, Robert A. Gross +1 more
Na+-dependent action potentials appear necessary for entrainment and expression of overt circadian rhythms, but they do not seem necessary for the pacemaker to keep accurate time.
Journal of NeuroscienceCalcium excitability and oscillations in suprachiasmatic nucleus neurons and glia in vitro
252 Citations1992AN van den Pol, SM Finkbeiner +1 more
To study the calcium responses of the cellular components that make up the clock, computer- controlled digital video and confocal scanning laser microscopy were used with the Ca2+ indicator dye fluo-3 to examine dispersed SCN cells and SCN explants with repeated sampling over time.
The Journal of Comparative Neurology<i>In vivo</i> metabolic activity of a putative circadian oscillator, the rat suprachiasmatic nucleus
229 Citations1980William J. Schwartz, Leslie Davidsen +1 more
These experiments indicate an important role for the SCN in circadian rhythm organization, and it is believed the deoxyglucose method will prove useful as a tool for better understanding the functions and mechanisms of circadian clocks.
ScienceCircadian Rhythm in Membrane Conductance Expressed in Isolated Neurons
206 Citations1993Stephan Michel, Michael E. Geusz +2 more
The persistence of daily conductance changes in isolated BRNs indicates that individual neurons can function as circadian pacemakers.
Journal of NeuroscienceThe suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14C-labeled deoxyglucose
206 Citations1984Steven M. Reppert, WJ Schwartz
The results show the utility of the deoxyglucose method for directly investigating prenatally the function of the biological clock located in the SCN.
Journal of Neuroscience MethodsSealing cultured invertebrate neurons to embedded dish electrodes facilitates long-term stimulation and recording
182 Citations1989Wade G. Regehr, Jerome Pine +3 more
A simple model is developed and tested that describes the voltage waveforms measured with array electrodes, and those measured from electrodes under cell bodies were primarily derivatives of the intracellular potential, while those measured under axon stumps were primarily proportional to local inward Na+ currents.
Journal of NeuroscienceSynaptogenesis in the rat suprachiasmatic nucleus demonstrated by electron microscopy and synapsin I immunoreactivity
178 Citations1989RY Moore, M.O. Bernstein
A correlation of these anatomical data with prior functional studies suggests that SCN neurons are born as individual circadian oscillators that undergo a rapid development in the first 10 days after birth to form a functional neural network subserving circadian rhythm generation and regulation.
Cell and Tissue ResearchImmunocytochemical localization of somatostatin-containing neurons in the rat hypothalamus
161 Citations1979Karen Dierickx, Frans Vandesande
The rat hypothalamus was studied at the light microscopic level with the use of single and double immunocytochemical staining methods and it was shown that the rat supraoptic and paraventricular hypothalamic nuclei, and their accessory neurosecretoryuclei, do not contain magnocellular somatostatin neurons.
NeuroscienceCellular communication in the circadian clock, the suprachiasmatic nucleus
148 Citations1993Anthony N. van den Pol, F. Edward Dudek
Some of the unanswered questions related to intercellular communication of suprachiasmatic nucleus cells are examined, including calcium spikes in presynaptic dendrites, ephaptic interaction, paracrine communication, glial mediation, and gap junctions.
Brain ResearchDispersed cell suspensions of fetal SCN restore circadian rhythmicity in SCN-lesioned adult hamsters
129 Citations1990Rae Silver, Michael N. Lehman +3 more
The results suggest that structural integrity of the fetal SCN is not necessary for restoration of rhythmicity after grafting, in contrast to intact hamsters and SCN-lesioned hamsters whose rhythms are restored by whole tissue grafts.
Neuroscience LettersDemonstration of GABAergic cell bodies in the suprachiasmatic nucleus: In situ hybridization of glutamic acid decarboxylase (GAD) mRNA and immunocytochemistry of GAD and GABA
126 Citations1989Hitoshi Okamura, Anne Bérod +5 more
Results indicate that GABA is a transmitter of a large portion of the SCN neuronal population and GAD protein and GABA were identified by immunocytochemistry using specific antisera.
Brain ResearchA possible glial role in the mammalian circadian clock
125 Citations1994Rebecca A. Prosser, Dale M. Edgar +2 more
It is suggested that glia play an important role in the SCN circadian clock by determining whether disrupting glial activity affects the in vitro circadian rhythm of neuronal activity and the in vivo circadian activity rhythm in rats.
Proceedings of the National Academy of SciencesNeuronal synchronization without calcium-dependent synaptic transmission in the hypothalamus.
116 Citations1993Yona Bouskila, F. Edward Dudek
It is reported that synchronous neuronal activity can occur in the hypothalamic suprachiasmatic nucleus without active Ca(2+)-dependent synaptic transmission and mechanisms other than Ca( 2+)- dependent synaptic transmission can synchronize neurons in the mammalian hypothalamus.
Journal of NeuroscienceMultielectrode analysis of coordinated, multisite, rhythmic bursting in cultured CNS monolayer networks
113 Citations1986MH Droge, G.W. Gross +2 more
The spontaneous appearance of rhythmic activity in low- density, monolayer cell cultures established from dissociated and randomly seeded spinal tissue can be explained by one or a combination of two hypotheses: an inherent specificity of some interconnections in developing mammalian cultures and the generation of organized activity by random circuits at certain stages of complexity.
Brain ResearchCircadian rhythms in spontaneous neuronal discharges of the cultured suprachiasmatic nucleus
111 Citations1990N. P. A. Bos, Majid Mirmiran
These organotypic explants, which had been cultured for several weeks in a chemically defined medium, showed alternating high and low levels of spontaneous neuronal discharges with a periodicity around 24 h, which can serve as a useful model to study the neuronal mechanisms underlying the generation of mammalian circadian rhythms.
Brain ResearchLong-term cultured neurons from rat suprachiasmatic nucleus retain the capacity for circadian oscillation of vasopressin release
109 Citations1991Noboru Murakami, Miho Takamure +4 more
This finding suggests that cultured SCN neurons retain the capacity for circadian oscillation for a long time, and should provide a useful model for the analysis of a mammalian circadian system at the cellular level.
Neuroendocrinologyc-fos Expression in Vasopressin and Oxytocin Neurons Reveals Functional Heterogeneity within Magnocellular Neurons
89 Citations2008Michelle Roberts, Alan Robinson +4 more
It is concluded that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.
Journal of Biological RhythmsMelatonin, the Pineal Gland, and Circadian Rhythms
77 Citations1993V.M. Cassone, Wade S. Warren +2 more
Data suggest that although pinealectomy does not affect rat circadian rhythms in light-dark cycles or constant darkness, wheel-running activity rhythms are severely disrupted in constant light, and that either (1) pineal feedback regulates the light sensitivity of the SCN, and/or (2) it affects coupling among circadian oscillators within the SCn or between theSCN and its output.
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyOn the nature of the circadian clock in mammals
73 Citations1993Joseph D. Miller
The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock.
Physiology & BehaviorLaboratory instrumentation and computing: Comparison of six methods for the determination of the period of circadian rhythms
72 Citations1993Roberto Refinetti
Fourier analysis and Enright's periodogram were superior to the other methods in the analysis of more complex waveforms (which more closely resemble actual circadian rhythms) and were more tolerant of low signal-to-noise ratios than the remaining methods.
Brain ResearchTetrodotoxin does not affect circadian rhythms in neuronal activity and metabolism in rodent suprachiasmatic nucleus in vitro
62 Citations1993Shigenobu Shibata, Robert Y. Moore
Single unit activity of suprachiasmatic nucleus (SCN) neurons recorded from hamster and rat hypothalamic slices in vitro exhibits a circadian rhythm in firing rate, in accord with the view that SCN neuron firing rate and glucose utilization is an expression of pacemaker activity but that pacemaker function is maintained in the SCN independent of neuronal function manifested by sodium dependent action potentials.
Brain ResearchIn vitro electrical activity in the suprachiasmatic nucleus following splitting and masking of wheel-running behavior
62 Citations1991Piotr Złomańczuk, Russell R. Margraf +1 more
The results indicate that in vitro electrical activity of the SCN is related to overt behavior in Djungarian hamsters, in that high electrical activity occurs when locomotor activity is minimal.
The Journal of PhysiologyMembrane properties of rat suprachiasmatic nucleus neurons receiving optic nerve input.
60 Citations1993Yang In Kim, F. Edward Dudek
The electrophysiological properties of suprachiasmatic nucleus (SCN) neurons receiving optic nerve input were studied with intracellular recordings in rat hypothalamic slices maintained in vitro to provide baseline data concerning the intrinsic membrane properties of these neurons and to test the hypothesis that the neurons are homogeneous Electrophysiologically.
Brain ResearchCircadian rhythms of vasopressin release in primary cultures of rat suprachiasmatic nucleus
59 Citations1993Kazuto Watanabe, Noriyuki Koibuchi +2 more
In all the cultures, the release of vasopressin showed clear circadian oscillation, which appeared within a few days in culture and lasted for more than a month.
NeuroscienceUnitary, quantal and miniature gaba-activated synaptic chloride currents in cultured neurons from the rat superior colliculus
40 Citations1992Kajetan Kraszewski, Rosemarie Grantyn
The conductance change induced by one quantum of gamma-aminobutyric acid from axonal release sites on cultured superior colliculus neurons was identified and indicates that one GABA quantum opened only 5-15 single Cl- channels.
Brain ResearchSpontaneous and stimulated firing in cultured rat suprachiasmatic neurons
33 Citations1992I.B. Walsh, R.J. van den Berg +2 more
The results indicate that cultured neurons have some electrophysiological properties in common with SCN neurons in brain slices and in vivo, and are likely to have spontaneous firing properties.
Developmental Brain ResearchElectrophysiological studies of the development of suprachiasmatic neuronal activity in hypothalamic slice preparations
26 Citations1984Shigenobu Shibata, Yutaka Oomura +2 more
The rate and pattern of neuronal discharge in the suprachiasmatic nucleus (SCN) during developmental stages were studied and compared with those of the ventromedial (VMH) and the lateral hypothalamus (LHA) using rat hypothalamic slices.
Brain ResearchUse of the patch electrode for sensitive high resolution extracellular recording
18 Citations1982Susan Forda, Thomas M. Jessell +2 more
Patch electrodes were discovered to be extremely sensitive extracellular electrodes, which can be used to detect the independent activity of very small neurites passing into the area of the patch, according to the resolution of the light microscope.
Neuroscience LettersSex differences in vasoactive intestinal peptide (VIP) concentrations in the anterior pituitary and hypothalamus of rats
13 Citations1989Peter Riskind, Janet M. Allen +3 more
Results support a possible role of VIP in the sexually dimorphic regulatory mechanisms of PRL secretion and demonstrate that hypothalamic and pituitary VIP levels vary in opposite directions, suggesting that VIP is differentially regulated at the two sites.
Brain ResearchImpulses of variable amplitude recorded from cell-attached patches on small hippocampal neurons
5 Citations1992Staffan Johansson, Peter Århem
Small cultured neurons from embryonic rat hippocampus were investigated with the cell-attached configuration of the patch-clamp technique, and the action potentials computed showed a considerable variation in amplitude.