Throughout the brain, astrocytes form networks mediated by gap junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecular gap junction channels shape neuronal network patterns remains unclear. Here, using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we show that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support. Using a facilitation-depression model, we identify neuronal afterhyperpolarization as the key parameter underlying bursting pattern regulation by extracellular potassium in mice with disconnected astrocytes. We confirm this prediction experimentally and reveal that astroglial network control of extracellular potassium sustains neuronal afterhyperpolarization via KCNQ voltage-gated K+ channels. Altogether, these data delineate how astroglial gap junctions mechanistically strengthen neuronal population bursts and point to approaches for controlling aberrant activity in neurological diseases.

• MeSH
• Action Potentials physiology   MeSH
• Astrocytes * metabolism   MeSH
• Potassium * metabolism   MeSH
• KCNQ Potassium Channels * metabolism   genetics   MeSH
• Hippocampus * metabolism   MeSH
• Connexins metabolism   genetics   MeSH
• Gap Junctions * metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Nerve Net metabolism   MeSH
• Neurons metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Large-conductance calcium-activated potassium channels (BK channels) are important regulators of neuronal excitability in the mammalian nervous system. BK channels are activated by changes in membrane electrical potential and intracellular calcium concentration and play a key role in shaping neuronal action potential. Indeed, under typical physiological conditions, opening of BK channels allows potassium ions to flow outside of the cell leading to membrane repolarization and fast afterhyperpolarization, thus controlling cellular excitability. These aspects are of direct relevance to a new study by Farajnia et al., 2015, reported in this issue of Neurobiology of Aging, on the role of BK channels in aging circadian clock neurons.

• MeSH
• Action Potentials physiology   MeSH
• Circadian Clocks genetics   physiology   MeSH
• Circadian Rhythm genetics   physiology   MeSH
• Potassium metabolism   MeSH
• Humans MeSH
• Membrane Potentials physiology   MeSH
• Neurons physiology   MeSH
• Suprachiasmatic Nucleus physiology   MeSH
• Aging genetics   physiology   MeSH
• Calcium metabolism   physiology   MeSH
• Large-Conductance Calcium-Activated Potassium Channels physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In the mammalian autonomic nervous system, tonic and phasic neurons can be differentiated on firing patterns in response to long depolarizing current pulse. However, the similar firing patterns in the somatic primary sensory neurons and their functional significance are not well investigated. Here, we identified two types of neurons innervating somatic sensory in rat dorsal root ganglia (DRG). Tonic neurons fire action potentials (APs) in an intensity-dependent manner, whereas phasic neurons typically generate only one AP firing at the onset of stimulation regardless of intensity. Combining retrograde labeling of somatic DRG neurons with fluorescent tracer DiI, we further find that these neurons demonstrate distinct changes under inflammatory pain states induced by complete Freund's adjuvant (CFA) or bee venom toxin melittin. In tonic neurons, CFA and melittin treatments significantly decrease rheobase and AP durations (depolarization and repolarization), enhance amplitudes of overshoot and afterhyperpolarization (AHP), and increase the number of evoked action potentials. In phasic neurons, however, the same inflammation treatments cause fewer changes in these electrophysiological parameters except for the increased overshoot and decreased AP durations. In the present study, we find that tonic neurons are more hyperexcitable than phasic neurons after peripheral noxious inflammatory stimulation. The results indicate the distinct contributions of two types of DRG neurons in inflammatory pain.

• MeSH
• Action Potentials physiology   MeSH
• Pain chemically induced   physiopathology   psychology   MeSH
• Behavior, Animal physiology   MeSH
• Electrophysiological Phenomena MeSH
• Freund's Adjuvant MeSH
• Rats MeSH
• Patch-Clamp Techniques MeSH
• Neurons physiology   MeSH
• Rats, Sprague-Dawley MeSH
• Ganglia, Spinal physiology   MeSH
• Inflammation chemically induced   physiopathology   psychology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH