Gap Junctions in the Brain: Physiological and Pathological Roles

It has been long thought that inter-cellular communication in the adult mammalian brain is exclusively mediated by neurotransmission at chemical synapses. However, evidence from molecular, biological, electrophysiological, pharmacological, and genetic approaches has accumulated indicating that electrical synapses (or gap junctions) in the adult brain also contribute to inter-cellular communication by the direct electrotonic and metabolic coupling of the cytosolic compartments of adjacent cells. Moreover, it has been discovered that gap junctions are important modulators of chemical neurotransmission and neuronal excitability.

Gap junctions between glial cells or neurons are ubiquitously expressed in the mammalian brain and play a role in brain development including cell differentiation, cell migration and survival, and tissue homeostasis, as well as in human diseases including hearing loss, neuropathies, epilepsy, brain trauma, and cardiovascular disease. Furthermore, gap junctions are involved in the synchronization and rhythmic oscillation of hippocampal and neocortical neuronal ensembles, which may be important for memory formation and consolidation. Moreover, the behavioral phenotyping of gap junction mutant mice has demonstrated the importance of gap junctions in the brain for various behaviors including motor behavior and memory performance. Further analysis of the molecular structural features of gap junctions may pave the way for the development of more selective pharmacological tools to modulate specific gap junctions, and ideally this will stimulate the development of novel gap junction–related treatments for human disease conditions.

Key Features:

• Most current and comprehensive reference available covering the physiological, behavioral and pathophysiological roles of gap junctions in the brain, geared for use by researchers, clinicians, and students.

• Chapters summarize knowledge of the basic physiology of gap junctions in the brain, as well as of human disease conditions associated with mutations in single gap junction connexin genes.

• Includes reviews of pharmacological studies with gap junction blockers and openers, summarizing information obtained from phenotyping gap junctions mouse mutants.

Ekrem Dere is full professor for the Pathophysiology of Cerebral Aging at the Pierre et Marie Curie University in Paris, France. His former team at the University in Düsseldorf, Germany, has provided the first behavioral evidence demonstrating that gap junctions in the brain play an important role in various behavioral processes.