Table 2.

Gap-junctional organization, connexin expression and functions in human adult brain. Stem cells are not included. Abbreviations: Astro., Astrocytes; BBB, Blood-brain barrier; CMT1X, X-linked Charcot-Marie-Tooth disease type 1; Compart., Compartments; Cx, Connexin; Ependym., Ependymocytes; Endo., Endothelial; GJ, Gap junction; GJIC, Gap-junctional intercellular communication; HC, Hemichannel; KO, Knock out mice; Neuroinflam., Neuroinflammation; NPC, Neuronal progenitor cells; ODDD, Oculodentodigital dysplasia; Oligo., Oligodendrocytes. References are indicated between brackets. In some cases, connexin function as GJIC and/or HC is questioned (?) because not proven yet [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98].

GJ Compart. /GJ Networks	Cellular Components		Connexin Expression				Brain-Related Physiological Effects of Cx Deficiency in:
	Cell Types	Major Cell Functions	Cx Types (Major Cxs)	Cx Functions		Principal Physiological Roles of Major Cxs	Mice (Cx Knock out)	Human (Cx Gene Defect)
				GJIC	HC
Neuronal	Neurons	Action potential transmission	Cx36 [25,26,27] Cx31.1 [23,29] Cx45 [30,31,32] Cx57 [33,34,35]	+ [27]	+ [28]	Electrical synapses (no synaptic delay): -Synchronization of interconnected neurons [27] -Excitability limitation in inhibitory networks [27] -Role in learning and memory [27]	Single KO Cx36: -Impaired short- and long-term memories [36,37] -Reduced motor learning [36,37]	Cx36: -Juvenile myoclonic epilepsy [38,39]
Panglial syncytium	Astrocytes	-Component of neuronal synapses (tripartite synapses) -BBB component (astrocytic endfeet)	Cx43 [40] Cx30 [40] Cx26 [41]	+ [42] + [42] ? [43]	+ [44] ?	-Glucose/lactate diffusion from capillaries to neurons and panglial syncytium (oligo., ependym.) [45] -K+ diffusion from neuron periphery and oligo. to capillaries [46,47] -Synaptic clearing of neurotransmitters, diffusion and recycling towards neurons [45] -Modulation of neuronal activity [48] -BBB maturation [49] -Gliosis and modulation of neuron activity through Cx43 HC activated by IL-1β/TNF-α (neuroinflam.) [50,51] or Ca2+/K+ [52,53,54]. Such activation leads to ATP release leading to paracrine/GJIC-mediated IP3/Ca2+ wave propagation (gliosis) [55] and gliotransmitters (glutamate) release (synaptic modulation) [56]	Single KO Cx43 (astro.): -Accelerated hippocampal spreading depression and enhanced locomotory activity [57] -Increased exploratory activity [58] -Anxiolytic-like effect in open field [58] Cx30: -Reduced exploratory activity -Anxiogenic behavior [59] Double KO Cx43 (astro.)/x30 [60]: -Vacuolated oligo. -Edematous astrocytes -Myelination abnormalities -Spatial memory impair -Sensimotor impair	Cx43: ODDD patients (according to mutations) [61]: -White matter change -Psychomotor delay -Epilepsy -Language disorder
	Oligo.	-Axon myelination to facilitate propagation of action potentials	Cx2 9[62] Cx32 [63] Cx47 [63]	? [64] + [62,65,66,67] + [62,65,66,67]	? [68]	-Myelin integrity [69] -K+ buffering from neuron periphery to astrocytes [63,70]	Single KO Cx29: -No myelin defect [71] Cx32 [72]: -Enhanced intrinsic excitability of neurons -Myelination defects in neocortex -Dysfunction of inhibitory synaptic transmission Cx47 [66]: -No behavior abnormality -Vacuolation of nerve fibers -Myelination abnormality Double KO Cx32/Cx47 [73]: -Myelination abnormality -Astrogliosis -Microglia activation Cx30/Cx47 [74]: -Myelination defects -Severe motor impairment -Decreased number of oligodendrocytes -Microglia activation	Cx32: CMT1X patients: -Mostly peripheral neuropathy [75] -Encephalopathy linked to metabolic stress (white matter lesions) [76] Cx47: Pelizaeus-Merzbacher-like disease [77,78]: -Myelination abnormality -Impaired psychomotor development
	Ependym.	-Lining cerebral cavities -Restrictive barrier between cerebrospinal and interstitial fluids -Facilitate circulation of cerebrospinal fluid by ciliated cells	Cx43 [79]	+ [79]
Vascular	Endo. cells	-Lining brain capillaries	Cx37 [80] Cx40 [80] Cx43 [80]	+ + +		-BBB integrity [81] -Maintenance and control of endothelial barrier function [81]		Cx37 polymorphism: -Ischemic stroke risk? [82]
	Pericytes	-Regulation of blood flow through contraction capacity	Cx37 [80] Cx40 [80] Cx43 [80]	+ + +		-Pericyte contraction? [83,84,85,86] -Maintenance of vascular homeostasis [81]
Other	Microglia	-Inflammation control -Phagocyte micro-organisms and damaged cells	Cx32 [87] Cx36 [88] Cx43 [89] (When activated)	? ? [88] (With neurons when activated) + [90,91]	+ [87] + [92]	-Neuron death [87] -Control of NPC proliferation, differentiation and migration [93,94,95,96,97] -Exchange of antigenic peptides? [98]