Precision of Inhibition: Dendritic Inhibition by Individual GABAergic Synapses on Hippocampal Pyramidal Cells Is Confined in Space and Time

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-08, Vol.87 (3), p.576-589
• Main Authors: Müllner, Fiona E., Wierenga, Corette J., Bonhoeffer, Tobias
• Format: Article
• Language: English
• Subjects: Acquisitions & mergers; Animals; Data analysis; Dendrites - physiology; GABAergic Neurons - physiology; Hippocampus - cytology; Hippocampus - physiology; Mice; Mice, Inbred C57BL; Neural Inhibition - physiology; Organ Culture Techniques; Pyramidal Cells - physiology; Rodents; Synapses - physiology; Time Factors
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.07.003

Inhibition plays a fundamental role in controlling neuronal activity in the brain. While perisomatic inhibition has been studied in detail, the majority of inhibitory synapses are found on dendritic shafts and are less well characterized. Here, we combine paired patch-clamp recordings and two-photon Ca2+ imaging to quantify inhibition exerted by individual GABAergic contacts on hippocampal pyramidal cell dendrites. We observed that Ca2+ transients from back-propagating action potentials were significantly reduced during simultaneous activation of individual nearby inhibitory contacts. The inhibition of Ca2+ transients depended on the precise spike-timing (time constant < 5 ms) and declined steeply in the proximal and distal direction (length constants 23–28 μm). Notably, Ca2+ amplitudes in spines were inhibited to the same degree as in the shaft. Given the known anatomical distribution of inhibitory synapses, our data suggest that the collective inhibitory input to a pyramidal cell is sufficient to control Ca2+ levels across the entire dendritic arbor with micrometer and millisecond precision. •New paradigm to measure inhibition by individual GABAergic synapses•A realistic model for dendritic Ca2+ inhibition•Ca2+ transients from back-propagating APs are inhibited with large dynamic range•Ca2+ is inhibited with micrometer/millisecond precision in both shafts and spines By imaging action potential-evoked dendritic calcium signals and simultaneously activating identified inhibitory synapses, Müllner et al. measured the spatio-temporal profile of inhibition exerted by individual GABAergic synapses, which fills a gap in the biophysical understanding of dendritic inhibition.