scholarly journals Cell type-specific transcriptional programs in mouse prefrontal cortex during adolescence and addiction

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aritra Bhattacherjee ◽  
Mohamed Nadhir Djekidel ◽  
Renchao Chen ◽  
Wenqiang Chen ◽  
Luis M. Tuesta ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cell Type ◽  
Cognitive Behaviors ◽  
Disease States ◽  
Transcriptional Dynamics ◽  
Chronic Cocaine ◽  
Transcriptional Changes ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Unique Cell

Abstract Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classify all unique cell subtypes in the PFC. We analyze transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.

scholarly journals Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens

2021 ◽  
Author(s):  
Hee-Dae Kim ◽  
Jing Wei ◽  
Tanessa Call ◽  
Nicole Teru Quintus ◽  
Alexander J. Summers ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Current Treatment ◽  
Specific Cell ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Circuit Function

AbstractDepression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

scholarly journals Cell-type-specific regulation of raft-associated Akt signaling

2011 ◽  
Vol 2 (4) ◽  
pp. e145-e145 ◽  
Author(s):  
Y Liu ◽  
G Yang ◽  
X Bu ◽  
G Liu ◽  
J Ding ◽  
...  
Keyword(s):  
Akt Signaling ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation

scholarly journals Quantitative synapse analysis for cell-type specific connectomics

2018 ◽  
Author(s):  
Dika A. Kuljis ◽  
Khaled Zemoura ◽  
Cheryl A. Telmer ◽  
Jiseok Lee ◽  
Eunsol Park ◽  
...  
Keyword(s):  
Large Scale ◽  
Neural Circuit ◽  
Apical Dendrite ◽  
Automated Detection ◽  
Cell Type ◽  
Disease States ◽  
Specific Localization ◽  
Cell Type Specific ◽  
Dendritic Branches ◽  
Circuit Function

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.

scholarly journals Cell Type-specific Regulation of RhoA Activity during Cytokinesis

2004 ◽  
Vol 279 (43) ◽  
pp. 44756-44762 ◽  
Author(s):  
Hisayoshi Yoshizaki ◽  
Yusuke Ohba ◽  
Maria-Carla Parrini ◽  
Natalya G. Dulyaninova ◽  
Anne R. Bresnick ◽  
...  
Keyword(s):  
Cell Type ◽  
Rhoa Activity ◽  
Cell Type Specific ◽  
Specific Regulation

scholarly journals Cell type-specific regulation of a replication origin residing within an AT-rich/LINE-1-rich isochore

Cell Cycle ◽  
2009 ◽  
Vol 8 (24) ◽  
pp. 4176-4178 ◽  
Author(s):  
Gennady Kholodii ◽  
Olga Dantsevich ◽  
Gleb Korobov ◽  
Vyacheslav Tarantul
Keyword(s):  
Replication Origin ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation
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