title: Spontaneous Activity Defines Effective Convergence Ratios in an Inhibitory Circuit.
abstract: Many neurons fire spontaneously, and the rate of this firing is subject to neuromodulation. How this firing affects functional connectivity within a neural network remains largely unexplored. Here we show that changes in spontaneous firing of cartwheel interneurons in the mouse dorsal cochlear nucleus (DCN) alter the effective convergence ratio of interneurons onto their postsynaptic targets through short-term synaptic plasticity. Spontaneous firing of cartwheel cells led to activity-dependent synaptic depression of individual cartwheel synapses. Depression was rapid and profound at stimulation frequencies between 10 and 200 Hz, suggesting the presence of high release probability (Pr) vesicles at these inhibitory synapses. Weak, transient synaptic facilitation could be induced after synapses were predepressed, indicating that low-Pr vesicles are also recruited, and may thus support steady-state transmission. A two-pool vesicle depletion model with 10-fold differences in Pr could account for the synaptic depression over a wide range of stimulus conditions. As a result of depression during high spontaneous activity, more cartwheel interneurons were required for effective inhibition. Convergence of four interneurons was sufficient to compensate for the effects of depression during physiologically expected rates of activity. By simulating synaptic release during spontaneous firing, we found that recruitment of low-Pr vesicles at the synapse plays a critical role in maintaining effective inhibition within a small population of interneurons. The interplay between spontaneous spiking, short-term synaptic plasticity, and vesicle recruitment thus determines the effective size of a convergent neural network.
  
  
  CONCLUSIONS
  We examined the relationship between the structure of a small neural circuit and the properties of its individual synapses. Successful synaptic inhibition of a target cell firing requires a critical inhibitory synaptic strength. Synapses often become depressed during spontaneous presynaptic activity, and this increases the number of presynaptic neurons needed to mediate inhibition. We show that depression is limited by the presence of a pool of vesicles that resist depletion. Thus, the size of this vesicle pool determines the size of the circuit needed to mediate inhibition during different patterns of activity.
authors.affiliation: Neuroscience Graduate Program and.
authors.forename: Hsin-Wei
authors.identifier: http://orcid.org/0000-0001-6352-8003
authors.initials: HW
authors.lastname: Lu
authors.affiliation: Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239 trussell@ohsu.edu.
authors.forename: Laurence O
authors.identifier: http://orcid.org/0000-0003-1171-2356
authors.initials: LO
authors.lastname: Trussell
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D017626:Cochlear Nucleus / Q000166:cytology*; D004558:Electric Stimulation; D050487:Glycine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D062308:Optogenetics; D018408:Patch-Clamp Techniques
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D050487:Glycine Plasma Membrane Transport Proteins; D008164:Luminescent Proteins; C493270:Slc6a5 protein, mouse; C054562:yellow fluorescent protein, Bacteria
keywords: auditory; depression; glycine; plasticity; vesicle