Targeted Patching and Dendritic Ca2+ Imaging in Nonhuman Primate Brain in vivo

Abstract

Nonhuman primates provide an important model not only for understanding human brain but also for translational research in neurological and psychiatric disorders. However, many high-resolution techniques for recording neural activity in vivo that were initially established for rodents have not been yet applied to the nonhuman primate brain. Here, we introduce a combination of two-photon targeted patching and dendritic Ca2+ imaging to the neocortex of adult common marmoset, an invaluable primate model for neuroscience research. Using targeted patching, we show both spontaneous and sensory-evoked intracellular dynamics of visually identified neurons in the marmoset cortex. Using two-photon Ca2+ imaging and intracellular pharmacological manipulation, we report both action-potential-associated global and synaptically-evoked NMDA (N-methyl-D-aspartate) receptor-mediated local Ca2+ signals in dendrites and spines of the superficial-layer cortical neurons. Therefore, we demonstrate the presence of synaptic Ca2+ signals in neuronal dendrites in living nonhuman primates. This work represents a proof-of-principle for exploring the primate brain functions in vivo by monitoring neural activity and morphology at a subcellular resolution.

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks

“…We demonstrated that two-photon calcium imaging can resolve dendritic and axonal activity in the marmoset, as has been shown in the mouse 4 , 63 , 64 . It may be possible to determine whether nonlinear dendritic computation is critical for higher brain functions in non-human primates 65 , 66 . The techniques developed in the present study have the potential to connect findings from rodent and primate research, which will help our understanding of the evolutional mechanisms through which higher motor and cognitive functions have been achieved.…”

Neural System Identification With Spike-Triggered Non-Negative Matrix Factorization

“…Our current results go one step further to uncover the functional identity and potential contribution of BC for its downstream GC. Recent advancements in experimental techniques make it possible to record simultaneously the signals in the soma and multiple dendrites with both imaging and electrophysiology [51], [52]. This protocol could provide an interesting test for the utility of STNMF.…”

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

“…In contrast to blind patch-clamp techniques, the “targeted patch-clamp” technique was developed by researchers to record membrane potentials from specific target cells in the neocortex. This method consists of “two-photon targeted patching” [ 49 , 50 ] and “shadow patching” [ 51 , 52 , 53 , 54 ].…”