Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Gap Junctions Compensate for Dendritic Integration



Science 30 March 2012: Vol. 335 no. 6076 pp. 1624-1628
Gap Junctions Compensate for Sublinear Dendritic Integration in an Inhibitory Network

Koen Vervaeke1, Andrea Lőrincz2, Zoltan Nusser2, R. Angus Silver1

1Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.

2Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Szigony utca 43, H-1083 Budapest, Hungary.


Electrically coupled inhibitory interneurons dynamically control network excitability, yet little is known about how chemical and electrical synapses regulate their activity. Using two-photon glutamate uncaging and dendritic patch-clamp recordings, we found that the dendrites of cerebellar Golgi interneurons acted as passive cables. They conferred distance-dependent sublinear synaptic integration and weakened distal excitatory inputs. Gap junctions were present at a higher density on distal dendrites and contributed substantially to membrane conductance. Depolarization of one Golgi cell increased firing in its neighbors, and inclusion of dendritic gap junctions in interneuron network models enabled distal excitatory synapses to drive network activity more effectively. Our results suggest that dendritic gap junctions counteract sublinear dendritic integration by enabling excitatory synaptic charge to spread into the dendrites of neighboring inhibitory interneurons.

Inhibitory interneurons balance network excitation, enhance spike-time precision of principal neurons, and control synchrony within and across brain regions. Yet, little is known about how interneurons integrate chemical and electrical synaptic inputs because of the inaccessibility of their dendrites. To investigate this, we studied dendritic integration in Golgi cells (GoCs), the main inhibitory interneurons in the input layer of the cerebellar cortex. GoCs receive excitatory mossy fiber (MF) and parallel fiber (PF) inputs onto their proximal and distal dendrites, respectively, and are predominantly interconnected by gap junctions (GJs). Two-photon uncaging of 4-methoxy-7-nitroindolinyl glutamate was used to mimic synaptic inputs at different dendritic locations. We tested the linearity of synaptic integration in a dendritic branch by comparing the arithmetic sum of individual photolysis-evoked excitatory postsynaptic potentials (pEPSPs), generated at different locations (section range 10 to 35 m; 18 5 m, 49 cells), with the response when all locations were activated synchronously (within a 3-ms window). For small pEPSPs, the synchronous response and arithmetic sum were similar, but for stronger pEPSPs, the integration became markedly sublinear. Sublinear integration was observed in apical and basolateral dendrites (0 to 261 m from soma, 120 54 m, 65 apical and 16 basolateral branches). However, for a given size of pEPSP recorded at the soma, sublinear dendritic integration became more pronounced with increasing distance from the soma.

In vivo, GoCs receive both synchronous and slowly modulated asynchronous synaptic inputs that are spatially distributed on the dendritic tree.

Our results show that the passive properties of GoC dendrites confer distance-dependent sublinear chemical synaptic integration. This weakens the impact of distal excitatory inputs. However, the high density of dendritic GJs in the molecular layer enables PF synaptic charge to flow into the dendrites of neighboring GoCs. This GJ-mediated lateral excitation counteracts the effects of sublinear dendritic behavior by enabling distal inputs to drive network activity more effectively. Dendritic GJs therefore counteract the problem of dendritic saturation without the need to boost electrically remote synaptic input with active dendritic conductances. A key role of interneurons is to counteract and balance network excitation. The combination of passive dendrites and dendritic GJs facilitates this by enabling a larger fraction of interneurons to respond to localized patches of synaptic excitation. Our results reveal how GJs on inhibitory interneuron dendrites could contribute to spatial averaging, which has been proposed in the retina and excitatory olfactory neurons in insects, and to the broad tuning of inhibitory interneurons in cortex. These mechanisms are also likely to contribute to gain control in the granule cell layer through PF-mediated feedback, and it seems likely that interneurons in cortical and subcortical structures use similar mechanisms. Our results suggest that interneurons do not operate as fully independent neuronal units but share charge during chemical synaptic excitation and thus exhibit features of a syncitium.

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