Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 1, Pages 504-509Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1308388110
Keywords
tonic conductance; extrasynaptic signaling; oscillations
Categories
Funding
- Wellcome Trust
- Epilepsy Research UK
- European Research Council and Cooperation in Science and Technology Action [BM1001]
- Royal Society
- Worshipful Company of Pewterers
- Ministry of Education and Science of Russian Federation [14.B37.21.0852]
- BBSRC [BB/J001473/1] Funding Source: UKRI
- MRC [G0900613] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J001473/1] Funding Source: researchfish
- Epilepsy Research UK [F0905] Funding Source: researchfish
- Medical Research Council [G0900613] Funding Source: researchfish
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The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABA(A) conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABA(A) depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABA(A) conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABA(A) conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABA(A) conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.
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