Continuous Electrical Oscillations Emerge from a Coupled Network: A Study of the Inferior Olive using Lentiviral Knockdown of Connexin36
Open Access
- 10 May 2006
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 26 (19), 5008-5016
- https://doi.org/10.1523/jneurosci.0146-06.2006
Abstract
Do continuous subthreshold oscillations in membrane potential within an electrically coupled network depend on gap junctional coupling? For the inferior olive (IO), modeling and developmental studies suggested that the answer is yes, although physiological studies of connexin36 knock-out mice lacking electrical coupling suggested that the answer is no. Here we addressed the question differently by using a lentivirus-based vector to express, in the IO of adult rats, a single amino acid mutation of connexin36 that disrupts the intracellular trafficking of wild-type connexin36 and blocks gap junctional coupling. Confocal microscopy of green fluorescence protein-labeled dendrites revealed that the mutant connexin36 prevented wild-type connexin36 from being expressed in dendritic spines of IO neurons. Intracellular recordings from lentivirally transduced IO networks revealed that robust and continuous subthreshold oscillations require gap junctional coupling of IO neuron somata within 40 μm of one another. Topological studies indicated that the minimal coupled network for supporting such oscillations may be confined to the dendritic arbor of a single IO neuron. Occasionally, genetically uncoupled IO neurons showed transient oscillations; however, these were not sustained longer than 3 s and were 69% slower and 71% smaller than the oscillations of normal IO neurons, a finding replicated with carbenoxolone, a pharmacological antagonist of gap junctions. The experiments provided the first direct evidence that gap junctional coupling between neurons, specifically mediated by connexin36, allows a continuous network oscillation to emerge from a population of weak and episodic single-cell oscillators. The findings are discussed in the context of the importance of gap junctions for cerebellar rhythms involved in movement.Keywords
This publication has 35 references indexed in Scilit:
- Block of Inferior Olive Gap Junctional Coupling Decreases Purkinje Cell Complex Spike Synchrony and RhythmicityJournal of Neuroscience, 2006
- Role of Gap Junctions in Synchronized Neuronal Oscillations in the Inferior OliveJournal of Neurophysiology, 2005
- Electrical synapses define networks of neocortical GABAergic neuronsTrends in Neurosciences, 2005
- Electrical coupling underlies theta oscillations recorded in hippocampal formation slicesBrain Research, 2004
- Carbenoxolone Inhibition of Voltage-Gated Ca Channels and Synaptic Transmission in the RetinaJournal of Neurophysiology, 2004
- ELECTRICAL SYNAPSES IN THE MAMMALIAN BRAINAnnual Review of Neuroscience, 2004
- Interneuron Diversity series: Inhibitory interneurons and network oscillations in vitroTrends in Neurosciences, 2003
- Evidence That Disruption of Connexon Particle Arrangements in Gap Junction Plaques Is Associated with Inhibition of Gap Junctional Communication by a Glycyrrhetinic Acid DerivativeExperimental Cell Research, 1996
- Dynamic organization of motor control within the olivocerebellar systemNature, 1995
- Development and properties of spontaneous oscillations of the membrane potential in inferior olivary neurons in the ratDevelopmental Brain Research, 1992