scholarly journals Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making

2021 ◽  
Author(s):  
Simon Musall ◽  
Xiaonan Richard Sun ◽  
Hemanth Mohan ◽  
Xu An ◽  
Steven Gluf ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Activity Patterns ◽  
Sensory Stimulation ◽  
Cell Types ◽  
Cortical Activity ◽  
Projection Neurons ◽  
Cortical Circuits ◽  
Cortical Dynamics ◽  
Functional Roles ◽  
Cell Type Specific

To understand how cortical circuits generate complex behavior, it is crucial to investigate the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed in sensory and frontal cortex, but it is not known whether these differences are the rule across all cortical areas or if different PyN types mostly follow the same cortex-wide dynamics. We used genetic and retrograde labeling to target pyramidal tract (PT), intratelencephalic (IT) and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics at a cortex-wide and within-area scale. Cortical activity and optogenetic inactivation during an auditory discrimination task also revealed distinct functional roles: all PyNs in parietal cortex were recruited during sensory stimulation but, surprisingly, PT neurons were most important for perception. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice-tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Connectivity Map ◽  
Analysis Techniques ◽  
Domain Specific ◽  
Cell Type Specific ◽  
Unique Domain

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

scholarly journals Cell type-specific membrane potential changes in dorsolateral striatum accompanying reward-based sensorimotor learning

Function ◽  
2021 ◽  
Author(s):  
Tanya Sippy ◽  
Corryn Chaimowitz ◽  
Sylvain Crochet ◽  
Carl C H Petersen
Keyword(s):  
Membrane Potential ◽  
Dopamine Receptors ◽  
Cell Types ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Cell Type ◽  
Indirect Pathway ◽  
Cell Type Specific ◽  
Striatal Membrane ◽  
Sensory Evoked

Abstract The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.

scholarly journals Transcriptome analysis for the development of cell-type specific labeling to study olfactory circuits

2020 ◽  
Author(s):  
Anzhelika Koldaeva ◽  
Cary Zhang ◽  
Yu-Pei Huang ◽  
Janine Reinert ◽  
Seiya Mizuno ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Mrna Level ◽  
Sensory System ◽  
Cell Types ◽  
Projection Neurons ◽  
Dependent Manner ◽  
Cell Type ◽  
Cell Type Specific ◽  
Sensory Evoked ◽  
Driver Line

AbstractIn each sensory system of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at some stage in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, little is known how these two types of projection neurons differ at the mRNA level. Here, we sought to identify genes that are differentially expressed between MCs and TCs, with an ultimate goal to generate a cell-type specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Despite many genes showing differential expressions, we identified only a few that were abundantly and consistently expressed only in MCs. After further validating these putative markers using in-situ hybridization, two genes, namely Pkib and Lbdh2, remained as promising candidates. Using CRISPR/Cas9-mediated gene editing, we generated Cre-driver lines and analysed the resulting recombination patterns. This analysis indicated that our new inducible Cre-driver line, Lbhd2-CreERT2, can be used to genetically label MCs in a tamoxifen dose-dependent manner, as assessed by soma locations, projection patterns and sensory-evoked responses. Hence this line is a promising tool for future investigations of cell-type specific contributions to olfactory processing and demonstrates the power of publicly accessible data in accelerating science.

scholarly journals Large-scale determination and characterization of cell type-specific regulatory elements in the human genome

2017 ◽  
Author(s):  
Can Wang ◽  
Shihua Zhang
Keyword(s):  
Histone Modifications ◽  
Large Scale ◽  
Chromatin Modification ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Type ◽  
Cell Identity ◽  
Functional Roles ◽  
Cancer Occurrence ◽  
Cell Type Specific

AbstractHistone modifications have been widely elucidated to play vital roles in gene regulation and cell identity. The Roadmap Epigenomics Consortium generated a reference catalogue of several key histone modifications across >100s of human cell types and tissues. Decoding these epigenomes into functional regulatory elements is a challenging task in computational biology. To this end, we adopted a differential chromatin modification analysis framework to comprehensively determine and characterize cell type-specific regulatory elements (CSREs) and their histone modification codes in the human epigenomes of five histone modifications across 127 tissues or cell types. The CSREs show significant relevance with cell type-specific biological functions and diseases and cell identity. Clustering of CSREs with their specificity signals reveals diverse histone codes, demonstrating the diversity of functional roles of CSREs within the same cell or tissue. Last but not least, dynamics of CSREs from close cell types or tissues can give a detailed view of developmental processes such as normal tissue development and cancer occurrence.

scholarly journals Functional annotation of lncRNA in high-throughput screening

2021 ◽  
Author(s):  
Chi Wai Yip ◽  
Divya M. Sivaraman ◽  
Anika V. Prabhu ◽  
Jay W. Shin
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Functional Annotation ◽  
Cell Types ◽  
Specific Expression ◽  
Functional Roles ◽  
Cellular Processes ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Abstract Recent efforts on the characterization of long non-coding RNAs (lncRNAs) revealed their functional roles in modulating diverse cellular processes. These include pluripotency maintenance, lineage commitment, carcinogenesis, and pathogenesis of various diseases. By interacting with DNA, RNA and protein, lncRNAs mediate multifaceted mechanisms to regulate transcription, RNA processing, RNA interference and translation. Of more than 173000 discovered lncRNAs, the majority remain functionally unknown. The cell type-specific expression and localization of the lncRNA also suggest potential distinct functions of lncRNAs across different cell types. This highlights the niche of identifying functional lncRNAs in different biological processes and diseases through high-throughput (HTP) screening. This review summarizes the current work performed and perspectives on HTP screening of functional lncRNAs where different technologies, platforms, cellular responses and the downstream analyses are discussed. We hope to provide a better picture in applying different technologies to facilitate functional annotation of lncRNA efficiently.

scholarly journals Connectivity characterization of the mouse basolateral amygdalar complex

2019 ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  
Keyword(s):  
Cell Body ◽  
Computational Analysis ◽  
Functional Characterization ◽  
Granular Cell ◽  
Cell Types ◽  
Projection Neurons ◽  
Cell Type ◽  
Analysis Techniques ◽  
Cell Type Specific

ABSTRACTThe basolateral amygdalar complex (BLA) is implicated in behavioral processing ranging from fear acquisition to addiction. Newer methods like optogenetics have enabled the association of circuit-specific functionality to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. In this work, we applied computational analysis techniques to the results of our circuit-tracing experiments to create a foundational, comprehensive, multiscale connectivity atlas of the mouse BLA. The analyses identified three domains within the classically defined anterior BLA (BLAa) that house target-specific projection neurons with distinguishable cell body and dendritic morphologies. Further, we identify brain-wide targets of projection neurons located in the three BLAa domains as well as in the posterior BLA (BLAp), ventral BLA (BLAv), lateral (LA), and posterior basomedial (BMAp) nuclei. Projection neurons that provide input to each nucleus are also identifed. Functional characterization of some projection-defined BLA neurons were demonstrated via optogenetic and recording experiments. Hypotheses relating function to connection-defined BLA cell types are proposed.

scholarly journals Hippocampal and thalamic afferents form distinct synaptic microcircuits in the mouse frontal cortex

2021 ◽  
Author(s):  
Kourtney Graham ◽  
Nelson Spruston ◽  
Erik B. Bloss
Keyword(s):  
Information Processing ◽  
Frontal Cortex ◽  
Cortical Neurons ◽  
Basolateral Amygdala ◽  
Cell Types ◽  
Brain Regions ◽  
Projection Neurons ◽  
Specific Cell ◽  
Nucleus Reuniens ◽  
Level Information

AbstractNeural circuits within the frontal cortex support the flexible selection of goal-directed behaviors by integrating input from brain regions associated with sensory, emotional, episodic, and semantic memory functions. From a connectomics perspective, determining how these disparate afferent inputs target their synapses to specific cell types in the frontal cortex may prove crucial in understanding circuit-level information processing. Here, we used monosynaptic retrograde rabies mapping to examine the distribution of afferent neurons targeting four distinct classes of local inhibitory interneurons and four distinct classes of excitatory projection neurons in mouse infralimbic cortex. Interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide received a large proportion of inputs from hippocampal regions, while interneurons expressing neuron-derived neurotrophic factor received a large proportion of inputs from thalamic regions. A more moderate hippocampal-thalamic dichotomy was found among the inputs targeting excitatory neurons that project to the basolateral amygdala, lateral entorhinal cortex, nucleus reuniens of the thalamus, and the periaqueductal gray. Together, these results show a prominent bias among hippocampal and thalamic afferent systems in their targeting to genetically or anatomically defined sets of frontal cortical neurons. Moreover, they suggest the presence of two distinct local microcircuits that control how different inputs govern frontal cortical information processing.

scholarly journals Diverse inhibitory projections from the cerebellar interposed nucleus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Elena N Judd ◽  
Samantha M Lewis ◽  
Abigail L Person
Keyword(s):  
Inferior Olive ◽  
Cell Types ◽  
Cerebellar Nuclei ◽  
Inhibitory Neurons ◽  
Cell Type ◽  
Functional Specificity ◽  
Functional Roles ◽  
Interposed Nucleus ◽  
Parallel Circuit ◽  
Cell Type Specific

The cerebellum consists of parallel circuit modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work employing cell-type-specific tracing has identified circumscribed output channels of the cerebellar nuclei (CbN) that could confer tight functional specificity. These studies have largely focused on excitatory projections of the CbN, however, leaving open the question of whether inhibitory neurons also constitute multiple output modules. We mapped output and input patterns to intersectionally restricted cell types of the interposed and adjacent interstitial nuclei in mice. In contrast to the widespread assumption of primarily excitatory outputs and restricted inferior olive-targeting inhibitory output, we found that inhibitory neurons from this region ramified widely within the brainstem, targeting both motor- and sensory-related nuclei, distinct from excitatory output targets. Despite differences in output targeting, monosynaptic rabies tracing revealed largely shared afferents to both cell classes. We discuss the potential novel functional roles for inhibitory outputs in the context of cerebellar theory.

scholarly journals Single-cell analysis of Foxp1-driven mechanisms essential for striatal development

2019 ◽  
Author(s):  
Ashley G. Anderson ◽  
Ashwinikumar Kulkarni ◽  
Matthew Harper ◽  
Genevieve Konopka
Keyword(s):  
Single Cell ◽  
Target Genes ◽  
Single Cell Analysis ◽  
Cell Types ◽  
Brain Regions ◽  
Projection Neurons ◽  
Loss Of Function ◽  
Cell Type ◽  
Motor Information ◽  
Cell Type Specific

AbstractThe striatum is a critical forebrain structure for integrating cognitive, sensory, and motor information from diverse brain regions into meaningful behavioral output. However, the transcriptional mechanisms that underlie striatal development and organization at single-cell resolution remain unknown. Here, we show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates organizational features of striatal circuitry in a cell-type-dependent fashion. Using single-cell RNA-sequencing, we examine the cellular diversity of the early postnatal striatum and find that cell-type-specific deletion ofFoxp1in striatal projection neurons alters the cellular composition and neurochemical architecture of the striatum. Importantly, using this approach, we identify the non-cell autonomous effects produced by disruptingFoxp1in one cell-type and the molecular compensation that occurs in other populations. Finally, we identify Foxp1-regulated target genes within distinct cell-types and connect these molecular changes to functional and behavioral deficits relevant to phenotypes described in patients withFOXP1loss-of-function mutations. These data reveal cell-type-specific transcriptional mechanisms underlying distinct features of striatal circuitry and identify Foxp1 as a key regulator of striatal development.

scholarly journals Gap Junctions Between Striatal D1 Neurons and Cholinergic Interneurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuqi Ren ◽  
Yang Liu ◽  
Minmin Luo
Keyword(s):  
Gap Junctions ◽  
Electrical Coupling ◽  
Cell Types ◽  
Projection Neurons ◽  
Chemical Synapse ◽  
Cell Type ◽  
Cholinergic Interneurons ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Cell Type Specific

The striatum participates in numerous important behaviors. Its principal projection neurons use GABA and peptides as neurotransmitters and interact extensively with interneurons, including cholinergic interneurons (ChIs) that are tonically active. Dissecting the interactions between projection neurons and ChIs is important for uncovering the role and mechanisms of the striatal microcircuits. Here, by combining several optogenetic tools with cell type-specific electrophysiological recordings, we uncovered direct electrical coupling between D1-type projection neurons and ChIs, in addition to the chemical transmission between these two major cell types. Optogenetic stimulation or inhibition led to bilateral current exchanges between D1 neurons and ChIs, which can be abolished by gap junction blockers. We further confirmed the presence of gap junctions through paired electrophysiological recordings and dye microinjections. Finally, we found that activating D1 neurons promotes basal activity of ChIs via gap junctions. Collectively, these results reveal the coexistence of the chemical synapse and gap junctions between D1 neurons and ChIs, which contributes to maintaining the tonically active firing patterns of ChIs.

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