scholarly journals Decreased Neuronal Excitability in Medial Prefrontal Cortex during Morphine Withdrawal is associated with enhanced SK channel activity and upregulation of small GTPase Rac1

Theranostics ◽  
2020 ◽  
Vol 10 (16) ◽  
pp. 7369-7383
Author(s):  
Liang Qu ◽  
Yuan Wang ◽  
Yang Li ◽  
Xin Wang ◽  
Nan Li ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Neuronal Excitability ◽  
Small Gtpase ◽  
Morphine Withdrawal ◽  
Channel Activity ◽  
Sk Channel

scholarly journals Constitutive Genetic Deletion of Hcn1 Increases Alcohol Preference during Adolescence

2020 ◽  
Vol 10 (11) ◽  
pp. 763
Author(s):  
Michael C. Salling ◽  
Neil L. Harrison
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Consumption ◽  
Medial Prefrontal Cortex ◽  
Neuronal Excitability ◽  
Cell Types ◽  
Brain Regions ◽  
Alcohol Preference ◽  
Hcn Channels ◽  
Direct Role ◽  
Genetic Deletion

The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (Ih), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in preclinical models of substance abuse including alcohol. In the prefrontal cortex of rodents, HCN expression and Ih magnitude are developmentally regulated during adolescence and may be vulnerable to alcohol’s effects. In mice, binge alcohol consumption during the adolescent period results in a sustained reduction in Ih that coincides with increased alcohol consumption in adulthood, yet the direct role HCN channels have on alcohol consumption are unknown. Here, we show that the genetic deletion of Hcn1 causes an increase in alcohol preference on intermittent 2-bottle choice task in homozygous null (HCN1−/−) male mice compared to wild-type littermates without affecting saccharine or quinine preference. The targeted viral deletion of HCN1 in pyramidal neurons of the medial prefrontal cortex resulted in a gradual loss of Hcn1 expression and a reduction in Ih magnitude during adolescence, however, this did not significantly affect alcohol consumption or preference. We conclude that while HCN1 regulates alcohol preference, the genetic deletion of Hcn1 in the medial prefrontal cortex does not appear to be the locus for this effect.

scholarly journals Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory

2008 ◽  
Vol 15 (3) ◽  
pp. 93-96 ◽  
Author(s):  
A. R. Brennan ◽  
B. Dolinsky ◽  
M.-A. T. Vu ◽  
M. Stanley ◽  
M. F. Yeckel ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Sk Channel

scholarly journals Secondhand Smoke Decreased Excitability and Altered Action Potential Characteristics of Cardiac Vagal Neurons in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Junqing Sun ◽  
Shiyue Pan ◽  
Emma Karey ◽  
Yi-Je Chen ◽  
Kent E. Pinkerton ◽  
...  
Keyword(s):  
Action Potential ◽  
Secondhand Smoke ◽  
Neuronal Excitability ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Nucleus Ambiguus ◽  
Channel Activity ◽  
Sk Channel ◽  
Cardiovascular Morbidity And Mortality ◽  
Shs Exposure

Background: Secondhand smoke (SHS), a major indoor pollutant, is a significant risk factor for cardiovascular morbidity and mortality including arrhythmias and sudden cardiac death. Exposure to SHS can produce autonomic imbalance, as evidenced by reduced heart rate variability (HRV)—a clinical metric of cardiac vagal regulation. Currently, the mechanisms through which SHS changes the vagal preganglionic neuronal inputs to the heart to produce this remains unknown.Objectives: To characterize the effect of SHS on both the excitability and action potential (AP) characteristics of anatomically identified cardiac vagal neurons (CVNs) in the nucleus ambiguus and examine whether SHS alters small conductance calcium-activated potassium (SK) channel activity of these CVNs.Methods: Adult male mice were exposed to four weeks of filtered air or SHS (3 mg/m3) 6 h/day, 5 day/week. Using patch-clamp recordings on identified CVNs in brainstem slices, we determined neuronal excitability and AP characteristics with depolarizing step- and ramp-current injections.Results: Four weeks of SHS exposure reduced spiking responses to depolarizing current injections and increased AP voltage threshold in CVNs. Perfusion with apamin (20 nM) magnified these SHS-induced effects, suggesting reduced SK channel activity may serve to minimize the SHS-induced decreases in CVNs excitability. Medium afterhyperpolarization (a measurement of SK channel activity) was smaller in the SHS group, further supporting a lower SK channel activity. AP amplitude, rise rate, fast afterhyperpolarization amplitude (a measurement of voltage-gated channel activity), and decay rate were higher in the SHS group at membrane voltages more positive to 0 mV, suggesting altered inactivation properties of voltage-dependent channels underlying APs.Discussion: SHS exposure reduced neuronal excitability of CVNs with compensatory attenuation of SK channel activity and altered AP characteristics. Neuroplasticity of CVNs could blunt regulatory cardiac vagal signaling and contribute to the cardiovascular consequences associated with SHS exposure, including reduced HRV.

scholarly journals Two contrasting mediodorsal thalamic circuits target the medial prefrontal cortex

2021 ◽  
Author(s):  
Polina Lyuboslavsky ◽  
Alena Kizimenko ◽  
Audrey C. Brumback
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Action Potentials ◽  
Brain Slices ◽  
Membrane Resistance ◽  
Channel Activity ◽  
Cholera Toxin Subunit B ◽  
Dendritic Arbors ◽  
Subunit B ◽  
Two Populations

ABSTRACTAt the heart of the prefrontal executive and limbic networks is the mediodorsal thalamus (MD). Despite the importance of MD in a broad range of behaviors and neuropsychiatric disorders, virtually nothing is known about the physiology of neurons in MD. Here, we injected the retrograde tracer cholera toxin subunit B (CTB) into the medial prefrontal cortex (mPFC) of adult (8 – 12 week old) male and female wildtype mice. We prepared acute brain slices and used current clamp electrophysiology to measure and compare the intrinsic properties of the neurons in MD that project to mPFC (MD→mPFC neurons). MD→mPFC neurons are located predominantly in the medial (MD-M) and lateral (MD-L) subnuclei of MD. We found that that MD-M→mPFC neurons have longer membrane time constants, higher membrane resistance, less Hyperpolarization and Cyclic Nucleotide gated (HCN) channel activity, and more readily generate action potentials compared to MD-L→mPFC neurons. Additionally, MD-M→mPFC neurons have larger and more complex dendritic arbors compared to MD-L→mPFC neurons. These data demonstrating that the two populations of MD→mPFC neurons have distinct physiologies and morphologies suggests a differential role in thalamocortical information processing and potentially behavior.

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