Summary Selecting and planning actions recruits neurons across many areas of the brain but how ensembles of neurons work together to make decisions is unknown. Temporally-coherent neural activity may provide a mechanism by which neurons coordinate their activity in order to make decisions. If so, neurons that are part of coherent ensembles may predict movement choices before other ensembles of neurons. We recorded neuronal activity in the lateral and medial banks of the intraparietal sulcus (IPS) of the posterior parietal cortex, while monkeys made choices about where to look and reach and decoded the activity to predict the choices. Ensembles of neurons that displayed coherent patterns of spiking activity extending across the IPS, “dual coherent” ensembles, predicted movement choices substantially earlier than other neuronal ensembles. We propose that dual-coherent spike timing reflects interactions between groups of neurons that play an important role in how we make decisions.
The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes, and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an important primate model system widely used in biomedical research2,3. The full heterozygosity spectrum between the two haplotypes involves 1.36% of the genome, much higher than the 0.13% indicated by the standard single nucleotide heterozygosity estimation alone. The de novo mutation rate is 0.43 × 10-8 per site per generation, where the paternal inherited genome acquired twice as many mutations as the maternal. Our diploid assembly enabled us to discover a recent expansion of the sex differentiated region and unique evolutionary changes in the marmoset Y chromosome. Additionally, we identified many genes with signatures of positive selection that might have contributed to the evolution of Callithrix biological features. Brain related genes were highly conserved between marmosets and humans, though several genes experienced lineage-specific copy number variations or diversifying selection, providing important implications for the application of marmosets as a model system.
Coherent neuronal dynamics play an important role in complex cognitive functions. Optogenetic stimulation promises to provide new ways to test the functional significance of coherent neural activity. However, the mechanisms by which optogenetic stimulation drives coherent dynamics remain unclear, especially in the nonhuman primate brain. Here, we perform computational modeling and experiments to study the mechanisms of optogenetic-stimulation-driven coherent neuronal dynamics in three male nonhuman primates. Neural responses arise from stimulation-evoked, temporally dynamic excitatory (E) and inhibitory (I) activity. Spiking activity is more likely to occur during E/I imbalances. Thus the relative difference in the driven E and I responses precisely controls spike timing by forming a brief time interval of increased spiking likelihood. Experimental results agree with parameter-dependent predictions from the computational models. These results demonstrate that optogenetic stimulation driven coherent neuronal dynamics are governed by the temporal properties of E/I activity. Transient imbalances in excitatory and inhibitory activity may provide a general mechanism for generating coherent neuronal dynamics without the need for an oscillatory generator.
30Coherent neuronal dynamics play an important role in complex cognitive functions, but the 31 causal role of neuronal coherence is unclear. Optogenetic stimulation allows causal tests of the 32 functional significance of coherent neuronal activity. While non-human primates are important 33 for studying the neural mechanisms of complex cognitive functions, optogenetic perturbation of 34 neuronal dynamics has had limited application in this animal model. Here, we develop a 35 computational framework and perform experiments to test how optogenetic stimulation perturbs 36 coherent neuronal dynamics. We show that stimulation-evoked neural responses arise from 37 temporal windows of excitatory and inhibitory activity that vary parametrically with optogenetic 38 stimulation parameters. We experimentally identify the effective temporal window of excitation 39 and inhibition and use the window in a computational model to design model-based stimulation 40 sequences. These results demonstrate optogenetic perturbations of coherent neuronal 41 dynamics and advance the use of optogenetic tools to study complex cognitive functions in the 42 primate brain. 43 44 7 132 Figure 1. Excitation and inhibition drive coherent neuronal dynamics. (A) During spontaneous 133 activity, synaptic inputs drive activity in a local network. We model spiking as being generated from 134 a Poisson process with a constant rate and LFP as being generated from a Brown noise process. 135 Under these assumptions, spontaneous spiking is not coherent with spontaneous LFP. (B) To 136 model optogenetic stimulation of a population of transduced neurons, we simulated pulsatile 137 responses generated by direct activation of ChR2 channels and synaptic activity. Pulsatile 138 responses are convolved with a stimulation sequence. The summed excitatory and inhibitory (E-I, 139 black) components comprise the simulated LFP. The individual E (blue) and I (red) activity govern 140 the variable spiking rate in the Poisson process which generates coherent spiking. (C) 141Spontaneous activity in the model has no spike-field coherence. (D) Optogenetic stimulation drives 142 correlated fields and spiking, leading to frequency selective spike-field coherence.
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