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Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates
W Breckinridge Carden1, Georgia M Alexander, David P Friedman
1Department Anatomical Sciences and Neurobiology, University of Louisville Health Sciences, Louisville, KY 40204, USA.
Background:
Chronic ethanol use is known to disrupt normal sleep rhythms, but the cellular basis for this disruption is unknown. An important contributor to normal sleep patterns is a low-threshold calcium current mediated by T-type calcium channels. The T-type calcium current underlies burst responses in thalamic nuclei that are important to spindle propagation, and we recently observed that this current is sensitive to acute low doses of ethanol.
Methods:
We used a combination of current clamp and voltage clamp recordings in an in vitro brain slice preparation of the dorsal lateral geniculate nucleus (LGN) of macaque monkeys that have chronically self-administered ethanol to determine whether chronic ethanol exposure may affect T-type currents.
Results:
Current clamp recordings from the LGN of ethanol naive macaques showed characteristic burst responses. However, recordings from the LGN in macaques that self-administered ethanol revealed a significant attenuation of bursts across a range of voltages (n=5). Voltage clamp recordings from control LGN neurons (n=16) and neurons (n=29) from brain slices from chronically drinking macaques showed no significant differences (P>0.05) in T-type current kinetics or in the membrane resistance of the thalamic cells between the two cohorts. However, mean T-type current amplitude measured in the chronically drinking animals was reduced by 31% (P<0.01).
Conclusions:
We conclude that chronic ethanol self-administration reduces calcium currents in thalamic relay cells without altering underlying current kinetics, which may provide a mechanistic framework for the well-documented disruptions in sleep/wake behavior in subjects with chronic ethanol exposure.
Insights
Chronic ethanol use disrupts sleep by reducing T-type calcium currents in thalamic relay cells. This study investigated the cellular mechanisms behind ethanol-induced sleep disturbances in macaque monkeys.
Area of Science:
- Neuroscience
- Sleep Research
- Pharmacology
Background:
- Chronic ethanol consumption disrupts sleep-wake cycles.
- T-type calcium channels mediate low-threshold calcium currents crucial for normal sleep patterns.
- These currents are essential for burst responses in thalamic nuclei, influencing sleep spindles.
Purpose of the Study:
- To investigate the impact of chronic ethanol self-administration on T-type calcium currents in the dorsal lateral geniculate nucleus (LGN).
- To determine the cellular basis for ethanol-induced sleep disruption.
Main Methods:
- Utilized in vitro brain slice preparations of the macaque monkey LGN.
- Employed current clamp and voltage clamp electrophysiological recordings.
- Compared neuronal activity in ethanol-naive and chronically ethanol-self-administering macaques.
Main Results:
- Chronic ethanol self-administration significantly attenuated burst responses in LGN neurons.
- No significant differences were observed in T-type current kinetics or membrane resistance.
- A 31% reduction in mean T-type current amplitude was measured in chronically drinking macaques.
Conclusions:
- Chronic ethanol self-administration reduces calcium currents in thalamic relay cells.
- This reduction occurs without altering the underlying kinetics of the currents.
- The findings provide a potential cellular mechanism for ethanol-related sleep/wake behavior disruptions.
