![]() In vibrissal sensory cortex layer 4, we used iGluSnFR3 to characterize distinct patterns of touch-evoked feedforward input from thalamocortical boutons and both feedforward and recurrent input onto L4 cortical neuron dendritic spines. Simultaneous imaging and electrophysiology at individual boutons in mouse visual cortex showed that iGluSnFR3 transients report single action potentials with high specificity. The resulting indicator iGluSnFR3 exhibits rapid nonsaturating activation kinetics and reports synaptic glutamate release with decreased saturation and increased specificity versus extrasynaptic signals in cultured neurons. We developed surface display constructs that improve iGluSnFR’s nanoscopic localization to postsynapses. Using a multiassay screen in bacteria, soluble protein and cultured neurons, we generated variants with improved signal-to-noise ratios and kinetics. However, existing iGluSnFR variants exhibit low in vivo signal-to-noise ratios, saturating activation kinetics and exclusion from postsynaptic densities. The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. Thus, direct assessment of the context dependence of place cell responses requires full control and separation of sensory cues.Glutamate indicators with improved activation kinetics and localization for imaging synaptic transmission Therefore, manipulation of a local object might change not only the sensory input when the animal gets close to it but also the input at many other locations. In addition, some cues, especially visual ones, can be accessible to the animal across a wide range of locations and distances. Indeed, multiple cues, across different modalities, can usually be perceived together by animals at a given location, making it difficult to completely alter all sensory features associated with one location. Although these experiments are informative, they face the potential confound that the level of context dependence exhibited might depend on how isolated the sensory cues were from one another. In addition, place-field locations are largely remapped when animals are placed in differently shaped chambers containing the same salient cue card 9. Consistent with this, physiological recordings revealed that, in some hippocampal neurons, responses produced by local objects depend on the object's position relative to other cues 7,8. However, the hippocampus is not required in tasks where the aversive stimulus was associated only with a single cue 6. Behavioral studies have shown that the hippocampus is indispensable in contextual fear conditioning, in which animals are trained to recognize a specific context where they received an aversive stimulus 6. Several lines of evidence have suggested that sensory responses in the hippocampus might be modulated by environmental context. In rodents, the firing fields of place cells follow the rotation of visual landmarks 3,4, and, in primates, 'spatial view cells' in the hippocampus become active when the animal fixates a particular object, indicating strong visual sensory drive 5. Pyramidal cells in the hippocampus were found to selectively fire action potentials when an animal enters a specific location within the environment 2, and it was shown that sensory cues exhibit substantial influence on the firing of these neurons. It is thus important to understand to what extent the hippocampus can differentiate the same sensory cue in different contexts and how such a computation is implemented.īehavioral and physiological studies have identified the hippocampus as a critical brain area encoding space 1. In even higher areas (for example, the hippocampus), sensory responses to a given cue might be strongly modulated by the particular context, which could be beneficial for navigation by preventing confusion when similar objects occur in distinct environments. Sensory input is processed at multiple locations in the brain, with responses in early sensory systems predominantly evoked by relatively simple features of instantaneous stimuli within localized receptive fields, whereas higher sensory areas encode more complex features. ![]() Position-variant sensory cues constitute a set of landmarks that guide animals during spatial navigation. (3) Howard Hughes Medical Institute, Department of Neuroscience, Baylor College of Medicine, Houston, USA ![]() (2) Max Planck Florida Institute for Neuroscience, Jupiter, USA (1) Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, USA Author(s): Xinyu Zhao 1, Yingxue Wang 1 2, Nelson Spruston 1, Jeffrey C. ![]()
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