TY - JOUR AB - Motor cortex (M1) exhibits a rich repertoire of neuronal activities to support the generation of complex movements. Although recent neuronal-network models capture many qualitative aspects of M1 dynamics, they can generate only a few distinct movements. Additionally, it is unclear how M1 efficiently controls movements over a wide range of shapes and speeds. We demonstrate that modulation of neuronal input–output gains in recurrent neuronal-network models with a fixed architecture can dramatically reorganize neuronal activity and thus downstream muscle outputs. Consistent with the observation of diffuse neuromodulatory projections to M1, a relatively small number of modulatory control units provide sufficient flexibility to adjust high-dimensional network activity using a simple reward-based learning rule. Furthermore, it is possible to assemble novel movements from previously learned primitives, and one can separately change movement speed while preserving movement shape. Our results provide a new perspective on the role of modulatory systems in controlling recurrent cortical activity. AU - Stroud, Jake P. AU - Porter, Mason A. AU - Hennequin, Guillaume AU - Vogels, Tim P ID - 8073 IS - 12 JF - Nature Neuroscience SN - 1097-6256 TI - Motor primitives in space and time via targeted gain modulation in cortical networks VL - 21 ER - TY - JOUR AB - Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that Caenorhabditis elegans O2-sensing neurons are tonic receptors that continuously signal ambient [O2] to set the animal's behavioral state. Sustained signaling relied on a Ca2+ relay involving L-type voltage-gated Ca2+ channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors. Tonic activity evoked continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O2]. Sustained O2 receptor signaling was propagated to downstream neural circuits, including the hub interneuron RMG. O2 receptors evoked similar locomotory states at particular O2 concentrations, regardless of previous d[O2]/dt. However, a phasic component of the URX receptors' response to high d[O2]/dt, as well as tonic-to-phasic transformations in downstream interneurons, enabled transient reorientation movements shaped by d[O2]/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change. AU - Busch, Karl Emanuel AU - Laurent, Patrick AU - Soltesz, Zoltan AU - Murphy, Robin Joseph AU - Faivre, Olivier AU - Hedwig, Berthold AU - Thomas, Martin AU - Smith, Heather L AU - de Bono, Mario ID - 6136 IS - 4 JF - Nature Neuroscience SN - 1097-6256 TI - Tonic signaling from O2 sensors sets neural circuit activity and behavioral state VL - 15 ER - TY - JOUR AB - CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. AU - Kim, Sooyun AU - Guzmán, José AU - Hu, Hua AU - Jonas, Peter M ID - 3258 IS - 4 JF - Nature Neuroscience SN - 1546-1726 TI - Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons VL - 15 ER - TY - JOUR AB - Recent theoretical work has provided a basic understanding of signal propagation in networks of spiking neurons, but mechanisms for gating and controlling these signals have not been investigated previously. Here we introduce an idea for the gating of multiple signals in cortical networks that combines principles of signal propagation with aspects of balanced networks. Specifically, we studied networks in which incoming excitatory signals are normally cancelled by locally evoked inhibition, leaving the targeted layer unresponsive. Transmission can be gated 'on' by modulating excitatory and inhibitory gains to upset this detailed balance. We illustrate gating through detailed balance in large networks of integrate-and-fire neurons. We show successful gating of multiple signals and study failure modes that produce effects reminiscent of clinically observed pathologies. Provided that the individual signals are detectable, detailed balance has a large capacity for gating multiple signals. AU - Vogels, Tim P AU - Abbott, L F ID - 8026 IS - 4 JF - Nature Neuroscience SN - 1097-6256 TI - Gating multiple signals through detailed balance of excitation and inhibition in spiking networks VL - 12 ER - TY - JOUR AB - Social and solitary feeding in natural Caenorhabditis elegans isolates are associated with two alleles of the orphan G-protein-coupled receptor (GPCR) NPR-1: social feeders contain NPR-1 215F, whereas solitary feeders contain NPR-1 215V. Here we identify FMRFamide-related neuropeptides (FaRPs) encoded by the flp-18 and flp-21 genes as NPR-1 ligands and show that these peptides can differentially activate the NPR-1 215F and NPR-1 215V receptors. Multicopy overexpression of flp-21 transformed wild social animals into solitary feeders. Conversely, a flp-21 deletion partially phenocopied the npr-1(null) phenotype, which is consistent with NPR-1 activation by FLP-21 in vivo but also implicates other ligands for NPR-1. Phylogenetic studies indicate that the dominant npr-1 215V allele likely arose from an ancestral npr-1 215F gene in C. elegans. Our data suggest a model in which solitary feeding evolved in an ancestral social strain of C. elegans by a gain-of-function mutation that modified the response of NPR-1 to FLP-18 and FLP-21 ligands. AU - Rogers, Candida AU - Reale, Vincenzina AU - Kim, Kyuhyung AU - Chatwin, Heather AU - Li, Chris AU - Evans, Peter AU - de Bono, Mario ID - 6156 IS - 11 JF - Nature Neuroscience SN - 1097-6256 TI - Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1 VL - 6 ER -