Nonlinear dendritic inhibition: A trickle that stops the wave

24 July 2020, 3.00 PM - 24 July 2020, 4.00 PM

Jan Schulz (University of Basel)


Hosted by the Computational Neuroscience Unit

GABAergic interneurons can be roughly divided according to their output targets as soma and dendrite-targeting, respectively. Parvalbumin (PV) positive interneurons, by far the most widely studied interneurons, provide powerful perisomatic inhibition. Inhibitory inputs from dendrite-targeting interneurons appear weak by comparison. However, experimental evidence from opto- and pharmacogenetic studies indicates that specifically dendrite-targeting interneurons powerfully control postsynaptic integration, synaptic plasticity and learning. The underlying mechanisms are not well understood. We recently showed that dendrite-targeting interneurons, including somatostatin positive OLM interneurons and NO-synthase positive neurogliaform cells, preferentially activate synaptic α5-subunit containing GABAARs (α5-GABAARs) in hippocampal CA1 pyramidal cells. Remarkably, α5-GABAAR-mediated IPSCs are strongly voltage-dependent and generate a 4-fold larger conductance above -50 mV than at rest. Thus, activation of these receptors can very effectively control voltage-dependent NMDAR activation in a dendrite branch-specific manner. Experiments in adult-born granule cells indicate that α5-GABAARs are initially expressed in all GABAergic synapses, but that they are selectively replaced by faster lower affinity GABAARs in perisomatic synapses targeted by PV interneurons during development. In addition to α5-GABAARs, neurogliaform cells are also known to activate dendritic GABABRs. GABABR activation directly inhibits dendritic Ca2+ spikes. In addition, the activation of G-coupled inward rectifying potassium (GIRK) channels in the dendrite profoundly alters the integrative properties of pyramidal neurons, although the direct effect of dendritic GIRK channels on the somatic membrane potential is negligible. Taken together, our observations show that dendritic inhibition effectively controls depolarization-induced electrogenesis in the dendrites while having only a minimal impact on the somatic membrane potential in the absence of excitatory inputs onto the targeted dendrites.

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