Optogenetic Inhibition of Medial Prefrontal Cortex–Pontine Nuclei Projections During the Stimulus-free Trace Interval Impairs Temporal Associative Motor Learning

Wu, Guohao; Liu, Shulei; Yao, Juan; Li, Xuan; Wu, Bing; Ye, Jian-Ning; Sui, Jian-feng

doi:10.1093/cercor/bhx238

Cited by 12 publications

(11 citation statements)

References 61 publications

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“…Firstly plasmid adeno-associated virus (pAAV) or control viruses were injected into the bilateral hippocampus. The viruses encode either the third-generation chloride pump halorhodopsin which was fused in-frame to enhanced yellow fluorescent protein (eNpHR3.0-EYFP) or only EYFP[30]. Both target genes are under control of the human synapsin I (hSyn) promoter (Fig 1A).…”

Section: Resultsmentioning

confidence: 99%

Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia

Fan

et al. 2019

PLoS ONE

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Schizophrenia (SZ) is a serious and incurable mental disorder characterized by clinical manifestations of positive and negative symptoms and cognitive dysfunction. High-frequency deep brain stimulation (DBS) of the ventral hippocampus (VHP) has been recently applied as a therapeutic approach for SZ in both experimental and clinical studies. However, little is known about the precise mechanism of VHP-DBS treatment for SZ and the role of hippocampal cell activation in the pathogenesis of SZ. With optogenetic technology in this study, we tried to inhibit neuronal activity in the VHP which has dense projections to the prefrontal cortex, before measuring long stumulus-induced delay eyeblink conditioning (long-dEBC) in a rodent model of SZ. Rats were administrated with phencyclidine (PCP, 3 mg/kg, 1/d, ip) for successive 7 days before optogenetic intervention. The current data show that PCP administration causes significant impairment in the acquisition and timing of long-dEBC; the inhibition of bilateral VHP neurons alleviates the decreased acquisition and impaired timing of longd-dEBC in PCP-administered rats. The results provide direct evidence at the cellular level that the inhibition of VHP neuronal cells may be a prominent effect of hippocampal DBS intervention, and increased activity in the hippocampal network play a pivotal role in SZ.

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Section: Resultsmentioning

confidence: 99%

Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia

Fan

et al. 2019

PLoS ONE

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“…Rats were anaesthetized with a mixture of ketamine (100 mg/kg, i.p., Gutian, Fujian, China) and xylazine (9 mg/kg, i.p., Sigma-Aldrich, St. Louis, MO, USA) and fixed in a stereotaxic apparatus (Model 942, David Kopf Instruments, Tujunga, California, USA) as described previously 17,18,109 . The virus was injected using a glass micropipette (tip diameter 10–20 µm) attached to a 5 µl Hamilton microsyringe (51189, Stoelting, Wood Dale, Illinois, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, the “averaged EMG amplitude” was analyzed by averaging EMG of individual rat over the valid trials and further averaged for each group. The learning (acquisition) criterion was at least 6 consecutive CRs with one acquisition training session 17,18,66,112,113 .…”

Section: Methodsmentioning

confidence: 99%

Reevaluating the ability of cerebellum in associative motor learning

Yao

Sun

et al. 2019

Sci Rep

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It has been well established that the cerebellum and its associated circuitry constitute the essential neuronal system for both delay and trace classical eyeblink conditioning (DEC and TEC). However, whether the cerebellum is sufficient to independently modulate the DEC, and TEC with a shorter trace interval remained controversial. Here, we used direct optogenetic stimulation of mossy fibers in the middle cerebellar peduncle (MCP) as a conditioned stimulus (CS) replacement for the peripheral CS (eg, a tone CS or a light CS) paired with a periorbital shock unconditioned stimulus (US) to examine the ability of the cerebellum to learn the DEC and the TEC with various trace intervals. Moreover, neural inputs to the pontine nucleus (PN) were pharmacological blocked to limit the associative motor learning inside the cerebellum. We show that all rats quickly acquired the DEC, indicating that direct optogenetic stimulation of mossy fibers in the left MCP is a very effective and sufficient CS to establish DEC and to limit the motor learning process inside the cerebellum. However, only five out of seven rats acquired the TEC with a 150-ms trace interval, three out of nine rats acquired the TEC with a 350-ms trace interval, and none of the rats acquired the TEC with a 500-ms trace interval. Moreover, pharmacological blocking glutamatergic and GABAergic inputs to the PN from the extra-cerebellar and cerebellar regions has no significant effect on the DEC and TEC learning with the optogenetic CS. These results indicate that the cerebellum has the ability to independently support both the simple DEC, and the TEC with a trace interval of 150 or 350 ms, but not the TEC with a trace interval of 500 ms. The present results are of great importance in our understanding of the mechanisms and ability of the cerebellum in associative motor learning and memory.

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“…Electrophysiological verification of pharmacogenetics was performed as previously described (37,(48)(49)(50)(51)(52). Twenty to 25 days after virus injection, the rats were anesthetized with 3% pentobarbital sodium (40 mg/kg, ip) and decapitated.…”

Section: Electrophysiological Verification Of Pharmacogeneticsmentioning

confidence: 99%

Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing

et al. 2022

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Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.

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Optogenetic Inhibition of Medial Prefrontal Cortex–Pontine Nuclei Projections During the Stimulus-free Trace Interval Impairs Temporal Associative Motor Learning

Cited by 12 publications

References 61 publications

Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia

Optogenetic inhibition of ventral hippocampal neurons alleviates associative motor learning dysfunction in a rodent model of schizophrenia

Reevaluating the ability of cerebellum in associative motor learning

Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing

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