Connexin36 vs. Connexin32, “miniature” neuronal gap junctions, and limited electrotonic coupling in rodent suprachiasmatic nucleus
Open accessAbstract
Suprachiasmatic nucleus (SCN) neurons generate circadian rhythms, and these neurons normally exhibit loosely-synchronized action potentials. Although electrotonic coupling has long been proposed to mediate this neuronal synchrony, ultrastructural studies have failed to detect gap junctions between SCN neurons. Nevertheless, it has been proposed that neuronal gap junctions exist in the SCN; that they consist of connexin32 or, alternatively, connexin36; and that connexin36 knockout eliminates neuronal coupling between SCN neurons and disrupts circadian rhythms. We used confocal immunofluorescence microscopy and freeze-fracture replica immunogold labeling to examine the distributions of connexin30, connexin32, connexin36, and connexin43 in rat and mouse SCN and used whole-cell recordings to re-assess electrotonic and tracer coupling. Connexin32-immunofluorescent puncta were essentially absent in SCN but connexin36 was relatively abundant. Fifteen neuronal gap junctions were identified ultrastructurally, all of which contained connexin36 but not connexin32, whereas nearby oligodendrocyte gap junctions contained connexin32. In adult SCN, one neuronal gap junction was >600 connexons, whereas 75% were smaller than 50 connexons, which may be below the limit of detectability by fluorescence microscopy and thin-section electron microscopy. Whole-cell recordings in hypothalamic slices revealed tracer coupling with neurobiotin in <5% of SCN neurons, and paired recordings (>40 pairs) did not reveal obvious electrotonic coupling or synchronized action potentials, consistent with few neurons possessing large gap junctions. However, most neurons had partial spikes or spikelets (often <1 mV), which remained after QX-314 [N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide] had blocked sodium-mediated action potentials within the recorded neuron, consistent with spikelet transmission via small gap junctions. Thus, a few "miniature" gap junctions on most SCN neurons appear to mediate weak electrotonic coupling between limited numbers of neuron pairs, thus accounting for frequent detection of partial spikes and hypothetically providing the basis for "loose" electrical or metabolic synchronization of electrical activity commonly observed in SCN neuronal populations during circadian rhythms.
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“For FRIL, we used five adult male and five adult female mice [four albino mice expressing GFP in locus ceruleus neurons (van den Pol et al., 2002; Rash et al., 2007b) (mice courtesy of Dr. Anthony van den Pol, Yale University, New Haven, CT), five C57BL, and one CL3], plus three adult male Sprague…”
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Identification of connexin36 in gap junctions between neurons in rodent locus coeruleus
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“data on gap junctions cannot be taken as proof that the requisite gap junctions do not exist: gap junctions can be very small (< 50 connexons) and hard to find (Rash et al., 2007), and gap junctions A”
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The computational power of the human brain
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Recent advances in freeze-fracture electron microscop: the replica immunolabeling technique
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Electrical Signaling with Neuronal Gap Junctions
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Circadian Regulation of Endocrine Functions
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The neural circadian system of mammals.
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The rat suprachiasmatic nucleus: the master clock ticks at 30 Hz
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Circadian Regulation of the Brain and Behavior: A Neuroendocrine Perspective
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Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses
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Genesis of the Master Circadian Pacemaker in Mice
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Different levels of circadian (de)synchrony – where does it hurt?
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Short-term propofol anaesthesia down-regulates clock genes expression in the master clock
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Estrogen‐mediated coupling via gap junctions in the suprachiasmatic nucleus
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Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain
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Excitatory Neuromodulator Reduces Dopamine Release, Enhancing Prolactin Secretion
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Connexins in the Nervous System
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Microcircuits of the Ventral Cochlear Nucleus
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For whom the bells toll: Networked circadian clocks
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What Role do Circadian Rhythms Play in Learning and Memory?
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Connexin and Pannexin Based Channels in the Nervous System
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Gap Junctions as Electrical Synapses
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Connexin36 localization to pinealocytes in the pineal gland of mouse and rat
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EFFECTS OF AGING AND INFLAMMATORY MOLECULES ON THE SUPRACHIASMATIC CIRCADIAN CLOCK
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Circadian Regulation of Endocrine Functions
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- Authors
- Rash, J. E., Olson, C. O., Pouliot, W. A., Davidson, K. G. V., Yasumura, T., Furman, C. S., Royer, S., Kamasawa, N., Nagy, J. I., & Dudek, F. E.
- Affiliations
- Colorado State University (US)
- University of Manitoba (CA)
- University of Utah (US)
- Southern Illinois University Carbondale (US)
- Corresponding author
- Rash, J.E.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 149
- Issue
- 2
- Pages
- 350-371
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2245895
- OpenAlex
- W2061677670
- Cited by
- 82
- References
- 93
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 11
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH55595)
- National Institute of Neurological Disorders and Stroke (NS44010, R01NS038121, NS 44395, NS-38121, R01NS044395, R01NS044010, NS39040, R21NS039040, R56NS044395)
- National Center for Research Resources (S10RR015706)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- suprachiasmatic nucleus, connexin 36, connexin 32, connexin 30, connexin 43, electrical coupling, circadian rhythm, neuronal synchronization, spikelet, QX-314
- MeSH terms
- Gap Junction beta-1 Protein, Gap Junction delta-2 Protein, Animals, Detergents, Electrophysiology, Freeze Fracturing, Immunohistochemistry, Male, Microscopy, Electron, Neuroglia, Neurons, Sodium Dodecyl Sulfate, Suprachiasmatic Nucleus, Rats, Sprague-Dawley, Gap Junctions, Connexins, Mice, Knockout, Patch-Clamp Techniques, Microscopy, Confocal, Mice, Rats
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