A Multimodal Multi‐Shank Fluorescence Neural Probe for Cell‐Type‐Specific Electrophysiology in Multiple Regions across a Neural Circuit (Adv. Sci. 2/2022)

AbstractAnatomical methods for determining cell-type specific connectivity are essential to inspire and constrain our understanding of neural circuit function. We developed new genetically-encoded reagents for fluorescence-synapse labeling and connectivity analysis in brain tissue, using a fluorogen-activating protein (FAP)-or YFP-coupled, postsynaptically-localized neuroligin-1 targeting sequence (FAP/YFPpost). Sparse viral expression of FAP/YFPpost with the cell-filling, red fluorophore dTomato (dTom) enabled high-throughput, compartment-specific localization of synapses across diverse neuron types in mouse somatosensory cortex. High-resolution confocal image stacks of virally-transduced neurons were used for 3D reconstructions of postsynaptic cells and automated detection of synaptic puncta. We took advantage of the bright, far-red emission of FAPpost puncta for multichannel fluorescence alignment of dendrites, synapses, and presynaptic neurites to assess subtype-specific inhibitory connectivity onto L2 neocortical pyramidal (Pyr) neurons. Quantitative and compartment-specific comparisons show that PV inputs are the dominant source of inhibition at both the soma and across all dendritic branches examined and were particularly concentrated at the primary apical dendrite, a previously unrecognized compartment of L2 Pyr neurons. Our fluorescence-based synapse labeling reagents will facilitate large-scale and cell-type specific quantitation of changes in synaptic connectivity across development, learning, and disease states.

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A cortico-collicular pathway for motor planning in a memory-dependent perceptual decision task

10.1101/709170 ◽

2019 ◽

Cited By ~ 1

Author(s):

Chunyu A. Duan ◽

Yuxin Pan ◽

Guofen Ma ◽

Taotao Zhou ◽

Siyu Zhang ◽

...

Keyword(s):

Brain Function ◽

Perturbation Methods ◽

Neural Circuit ◽

Dynamic Environment ◽

Motor Planning ◽

Decision Task ◽

Cell Type ◽

Perceptual Decision ◽

Cell Type Specific ◽

Sensory Evidence

ABSTRACTSurvival in a dynamic environment requires animals to plan future actions based on past sensory evidence. However, the neural circuit mechanism underlying this crucial brain function, referred to as motor planning, remains unclear. Here, we employ projection-specific imaging and perturbation methods to investigate the direct pathway linking two key nodes in the motor planning network, the secondary motor cortex (M2) and the midbrain superior colliculus (SC), in mice performing a memory-dependent perceptual decision task. We find dynamic coding of choice information in SC-projecting M2 neurons during motor planning and execution, and disruption of this information by inhibiting M2 terminals in SC selectively impaired decision maintenance. Furthermore, cell-type-specific optogenetic circuit mapping shows that M2 terminals modulate both excitatory and inhibitory SC neurons with balanced synaptic strength. Together, our results reveal the dynamic recruitment of the premotor-collicular pathway as a circuit mechanism for motor planning.

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Cell-type specific patterned stimulus-independent neuronal activity in the Drosophila visual system during synapse formation

10.1101/376871 ◽

2018 ◽

Author(s):

Orkun Akin ◽

Bryce T. Bajar ◽

Mehmet F. Keles ◽

Mark A. Frye ◽

S. Lawrence Zipursky

Keyword(s):

Visual System ◽

Synapse Formation ◽

Neural Circuit ◽

Specific Activity ◽

System Development ◽

Nervous System Development ◽

Adult Brain ◽

Cell Type ◽

Cell Type Specific

SummaryStereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 examined of the over 100 specific neuron types in the fly visual system exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell type-specific activity coordinates the development of the functional circuitry of the adult brain.

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Simultaneous electrophysiological recording and fiber photometry in freely behaving mice

10.1101/807602 ◽

2019 ◽

Cited By ~ 2

Author(s):

Amisha A Patel ◽

Niall McAlinden ◽

Keith Mathieson ◽

Shuzo Sakata

Keyword(s):

Neural Circuit ◽

Electrophysiological Recording ◽

Field Potentials ◽

Cell Type ◽

Specific Population ◽

Population Activity ◽

Custom Made ◽

Cell Type Specific ◽

Freely Behaving

AbstractIn vivo electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial task. Over the last decade, fiber photometry based on genetically encoded calcium indicators has been widely adopted as a versatile tool to monitor cell-type-specific population activity in vivo. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system, and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free pontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that pontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics in vivo.

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Spatial and temporal locomotor learning in mouse cerebellum

10.1101/389965 ◽

2018 ◽

Author(s):

Dana M. Darmohray ◽

Jovin R. Jacobs ◽

Hugo G. Marques ◽

Megan R. Carey

Keyword(s):

Neural Circuit ◽

Human Learning ◽

Interlimb Coordination ◽

The Body ◽

Whole Body ◽

Cell Type ◽

Body Movements ◽

Locomotor Adaptation ◽

Cell Type Specific ◽

Context Specific

AbstractStable and efficient locomotion requires precise coordination of whole-body movements. Learned changes in interlimb coordination can be induced by exposure to a split-belt treadmill that imposes different speeds under each side of the body. Here we show that mice adapt to split-belt walking in a way that is remarkably similar to humans, suggesting that this form of locomotor learning is highly conserved across vertebrates. Like human learning, mouse locomotor adaptation is specific to measures of interlimb coordination, has spatial and temporal components that adapt at different rates, and is highly context-specific. Using a variety of approaches, we demonstrate that split-belt adaptation in mice specifically depends on intermediate cerebellum, but is insensitive to large lesions of cerebral cortex. Finally, cell-type specific chemogenetics combined with quantitative behavioral analysis reveal distinct neural circuit mechanisms underlying spatialvs. temporal components of locomotor adaptation.

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