Mapping big brains at subcellular resolution in the era of big data in zoology

Connectome-scale structural mapping is fundamental for understanding the underlying mechanisms of brain cognition and brain disease pathogenesis.By combining rapidly developing three-dimensional(3D)imaging techniques and big data analysis methods,researchers are working on mesoscale mapping of mammalian brains at an accelerated pace.Here,we briefly describe existing brain-wide imaging strategies,especially our recently established primateoptimized pipeline capable of pan-brain neuronal connectivity mapping at subcellular resolution,and further discuss their vast application prospects in the big data era of zoology.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal

Acetylcholine(ACh)is an important neuromod-ulator in various cognitive functions.However,it is unclear how ACh influences neural circuit dynamics by altering cellular properties.Here,we investigated how ACh influ-ences reverberatory activity in cultured neuronal networks.We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses,but to a much lesser extent at high doses.Moreover,high doses of ACh caused a longer duration of evoked reverberation,and a higher occur-rence of spontaneous activity.With whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal firing in a dose-dependent manner.Furthermore,all ACh-induced cellular and network changes were blocked by muscarinic,but not nicotinic receptor antagonists.With computational modeling,we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations.Thus,ACh modulates network dynamics in a biphasic fashion,probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

Conserved Spatiotemporal Dynamics with Millisecond Precision During Reverberatory Activity in a Self-organized Neuronal

Dear Editor,The timing of spiking activity across neurons is believed to play an important role in information coding in brain circuits1[1].At the cellular level,neurons can fire spikes with millisecond precision and the relative timing of pre-and postsynaptic spikes can determine the direction and extent of synaptic modification[2].When such spike-timing-dependent plasticity(STDP)and other physiological and anatomical properties are implemented in theoretical models,the simulated networks of interconnected spiking neurons exhibit neuronal groups with stereotypical time-locked spatiotemporal firing patterns with millisecond temporal precision[3].