scholarly journals Downregulation of HCN1 Channels in Hippocampus and Prefrontal Cortex in Methamphetamine Re-Exposed Mice With Enhanced Working Memory

2019 ◽  
pp. 107-117 ◽  
Author(s):  
Mei Zhou ◽  
Kuan Lin ◽  
Yuanren Si ◽  
Qin R ◽  
Lin Chen ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Protein Expression ◽  
Memory Function ◽  
Morris Water Maze Test ◽  
Hcn Channels ◽  
Protein Expressions ◽  
Important Regulator ◽  
Hcn1 Channels

The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a potential role in the neurological basis underlying drug addiction. However, little is known about the role of HCN channels in methamphetamine (METH) abuse. In the present study, we examined the changes in working memory functions of METH re-exposed mice through Morris water maze test, and investigated the protein expression of HCN1 channels and potential mechanisms underlying the modulation of HCN channels by Western blotting analysis. Mice were injected with METH (1 mg/kg, i.p.) once per day for 6 consecutive days. After 5 days without METH, mice were re-exposed to METH at the same concentration. We found that METH re-exposure caused an enhancement of working memory, and a decrease in the HCN1 channels protein expression in both hippocampus and prefrontal cortex. The phosphorylated extracellular regulated protein kinase 1/2 (p-ERK1/2), an important regulator of HCN channels, was also obviously reduced in hippocampus and prefrontal cortex of mice with METH re-exposure. Meanwhile, acute METH exposure did not affect the working memory function and the protein expressions of HCN1 channels and p-ERK1/2. Overall, our data firstly showed the aberrant protein expression of HCN1 channels in METH re-exposed mice with enhanced working memory, which was probably related to the down-regulation of p-ERK1/2 protein expression.

scholarly journals A Possible Link Between HCN Channels and Depression

2018 ◽  
Vol 2 ◽  
pp. 247054701878778 ◽  
Author(s):  
Chung Sub Kim ◽  
Daniel Johnston
Keyword(s):  
Protein Expression ◽  
Neuronal Excitability ◽  
Acute Stress ◽  
Hcn Channels ◽  
Chronic Unpredictable Stress ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hcn1 Channels ◽  
The Brain

Growing evidence suggests a possible link between hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels and depression. In a recent study published in Molecular Psychiatry, we first demonstrate that Ih (the membrane current mediated by HCN channels) and HCN1 protein expression were increased in dorsal, but not in ventral, CA1 region following chronic, but not acute stress. This upregulation of Ih was restricted to the perisomatic region of CA1 neurons and contributed to a reduction of neuronal excitability. A reduction of HCN1 protein expression in dorsal CA1 region before the onset of chronic unpredictable stress-induced depression was sufficient to provide resilient effects to chronic unpredictable stress. Furthermore, in vivo block of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pumps, a manipulation known to increase intracellular calcium levels and upregulate Ih, produced anxiogenic-like behavior and an increase in Ih, similar to that observed in chronic unpredictable stress model of depression. Here, we share our view on (1) how the function and expression of HCN1 channels are changed in the brain in a subcellular region-specific manner during the development of depression and (2) how a reduction of HCN1 protein expression provides resilience to chronic stress.

scholarly journals Role of prefrontal cortex and the midbrain dopamine system in working memory updating

2012 ◽  
Vol 109 (49) ◽  
pp. 19900-19909 ◽  
Author(s):  
K. D'Ardenne ◽  
N. Eshel ◽  
J. Luka ◽  
A. Lenartowicz ◽  
L. E. Nystrom ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dopamine System ◽  
Memory Updating ◽  
Working Memory Updating ◽  
Midbrain Dopamine

scholarly journals Integration in Working Memory: A Magnetic Stimulation Study on the Role of Left Anterior Prefrontal Cortex

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43731 ◽  
Author(s):  
Nicola De Pisapia ◽  
Marco Sandrini ◽  
Todd S. Braver ◽  
Luigi Cattaneo
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Magnetic Stimulation ◽  
Anterior Prefrontal Cortex

The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task

1994 ◽  
Vol 71 (2) ◽  
pp. 515-528 ◽  
Author(s):  
T. Sawaguchi ◽  
P. S. Goldman-Rakic
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Injection Site ◽  
Target Location ◽  
Dopamine Antagonists ◽  
Dopamine Antagonist ◽  
Delayed Response ◽  
Intracerebral Injection ◽  
Control Task

1. To examine the role of dopamine receptors in the prefrontal cortex (PFC) on working memory, we injected dopamine antagonists (SCH23390, SCH39166, haloperidol, sulpiride, and raclopride) locally into the dorsolateral PFC in two monkeys trained to perform an oculomotor delayed-response (ODR) task. In the ODR task, monkeys fixate a central spot on a cathode ray tube (CRT) monitor while a visual cue is briefly (300 ms) presented in one of several peripheral locations in the visual field. After a delay of 1.5-6 s, the fixation spot is turned off, instructing the monkey to move its eyes to the target location that had been indicated by the visuospatial cue before the delay. Each monkey also performed a control task in which the cue remained on during the delay period. In this task the monkey's response was sensory rather than memory guided. 2. Local intracerebral injection of the selective dopamine antagonists SCH23390 (10-80 micrograms) and SCH39166 (1-5 micrograms) and/or the nonselective dopamine antagonist haloperidol (10-100 micrograms) induced deficits in ODR task performance at a total of 22 sites in the dorsolateral PFC. The deficit was characterized by a decrease in the accuracy of the memory-guided saccade as well as an increase in the latency of the response. The deficit usually appeared within 1-3 min after the injection, reached a peak at 20-40 min, and recovered at 60-90 min. 3. Performance change was restricted to a few specific target locations, which varied with the injection site and were most often contralateral to the injection site. 4. The degree of impairment in the ODR task occasioned by the injection of the dopamine antagonists was sensitive to the duration of delay; longer delays were associated with larger decreases in the accuracy and delayed onset of the memory-guided saccade. 5. The deficit was dose dependent; higher doses induced larger errors and increases in the onset of the memory-guided saccade. 6. Dopamine antagonists did not affect performance on the control task, which required the same eye movements but was sensory guided. Thus, in the same experimental session in which ODR performance was impaired, the accuracy and the latency of the sensory-guided saccades were normal for every target location.(ABSTRACT TRUNCATED AT 400 WORDS)

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