Gap junctions are paired membrane specializations composed of dense clusters of tubular transmembrane channels (connexons) that link head to head across the extracellular space, forming pathways for direct electrical coupling and intercellular exchange of ions and low molecular weight metabolites. In mammals, gap junctions are abundant between glial cells and recently have been discovered at """"""""mixed"""""""" (electrical plus chemical) synapses between neurons. Gap junctions are composed of one or more of the 21 different connexin proteins identified in the two draft human genome sequences. At least 13 connexin proteins are expressed in mammalian CNS. Currently, there is considerable controversy as to which connexins are present in neurons vs. glia, and whether neurons are coupled to glia through conjoint gap junctions. Glial gap junctions provide pathways for maintaining ionic homeostasis throughout the CNS, whereas neuronal gap junctions, particularly those at mixed synapses, may underlie the production of high-frequency oscillations in neurons as the substrate for conscious perception and arousal from sleep, and they may be involved in the synchronous bursting activity of epilepsy. Because the specific pairing combinations of the several connexins expressed in each gap junction plaque provide for metabolic, voltage, and ionic regulation of gap junction conductance and gating properties, it is essential to determine the connexin composition of both neuronal and glial gap junctions in normal adult animals. It also is essential to determine if, in addition to linking neurons, gap junctions link neurons to glia. Thus, the long-term goals of the proposed research are to determine the relative abundance, histological and ultrastructural distribution, cellular coupling partners, and connexin compositions of gap junctions in neurons and glia in adult mammalian CNS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044395-03
Application #
6757220
Study Section
Special Emphasis Panel (ZRG1-MDCN-4 (01))
Program Officer
Stewart, Randall R
Project Start
2002-07-01
Project End
2007-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
3
Fiscal Year
2004
Total Cost
$326,800
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Nagy, James I; Pereda, Alberto E; Rash, John E (2018) Electrical synapses in mammalian CNS: Past eras, present focus and future directions. Biochim Biophys Acta Biomembr 1860:102-123
Nagy, James I; Pereda, Alberto E; Rash, John E (2017) On the occurrence and enigmatic functions of mixed (chemical plus electrical) synapses in the mammalian CNS. Neurosci Lett :
Wang, S G; Tsao, D D; Vanderpool, K G et al. (2017) Connexin36 localization to pinealocytes in the pineal gland of mouse and rat. Eur J Neurosci 45:1594-1605
Rash, J E; Kamasawa, N; Vanderpool, K G et al. (2015) Heterotypic gap junctions at glutamatergic mixed synapses are abundant in goldfish brain. Neuroscience 285:166-93
Yao, Cong; Vanderpool, Kimberly G; Delfiner, Matthew et al. (2014) Electrical synaptic transmission in developing zebrafish: properties and molecular composition of gap junctions at a central auditory synapse. J Neurophysiol 112:2102-13
Bautista, W; Rash, J E; Vanderpool, K G et al. (2014) Re-evaluation of connexins associated with motoneurons in rodent spinal cord, sexually dimorphic motor nuclei and trigeminal motor nucleus. Eur J Neurosci 39:757-70
Serrano-Velez, Jose L; Rodriguez-Alvarado, Melanie; Torres-Vazquez, Irma I et al. (2014) Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons. Front Neural Circuits 8:66
Nagy, James Imre; Urena-Ramirez, Viridiana; Ghia, Jean-Eric (2014) Functional alterations in gut contractility after connexin36 ablation and evidence for gap junctions forming electrical synapses between nitrergic enteric neurons. FEBS Lett 588:1480-90
Bautista, W; McCrea, D A; Nagy, J I (2014) Connexin36 identified at morphologically mixed chemical/electrical synapses on trigeminal motoneurons and at primary afferent terminals on spinal cord neurons in adult mouse and rat. Neuroscience 263:159-80
Bautista, W; Nagy, J I (2014) Connexin36 in gap junctions forming electrical synapses between motoneurons in sexually dimorphic motor nuclei in spinal cord of rat and mouse. Eur J Neurosci 39:771-87

Showing the most recent 10 out of 48 publications