Event

GABAA receptors mediate two forms of signaling in the brain: phasic and tonic. Phasic signaling (e.g., IPSCs) is mediated by synaptic GABAA receptors, while tonic signaling (e.g., tonic current or tonic conductance) is mediated by extrasynaptic GABAA receptors. Tonic current is expressed in a cell-type specific manner and is mediated by heterogeneous and plastic GABAA receptors. These receptors are activated by ambient GABA that originates from vesicular and non-vesicular sources and is regulated by different GABA transporter systems. Tonic GABAA conductance is commonly referred as tonic inhibition. We found that ambient GABA can actually excite adult hippocampal interneurons. In these cells, the GABAA reversal potential is depolarizing, making baseline tonic GABAA conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Because hippocampal interneurons are the key to setting the network rhythms this mechanism allows bidirectional control of network synchronization by tonic GABAA receptor-mediated signaling. We also show that tonic GABAA conductance decreases the membrane time constant (τm) and improves the temporal fidelity of EPSP-spike coupling. Long-term potentiation (LTP) induced by different stimulation patterns is differently affected by tonic GABAA conductance. Our findings thus point to an important role of extrasynaptic signaling mediated by GABAA receptors in brain computations.