In vivo microinjections of cholinergic compounds into the medial pontine reticular formation have produced some or depending on the injection site, all of the phenomena of REM, thus providing the only adequate pharmacological model of this behavioral state. The necessary anatomical substrate, a cholinergic projection to the mPRF was recently demonstrated, however the direct effect of cholinergic agonists on mPRF neurons is unknown. We have examined the effects of carbachol on mPRF neurons recorded in vitro from brainstem slices of Sprague-Dawley rats (8-10 days old). Three kinds of response to the application of carbachol (0.5-1 microM) were observed (n = 15) as follows: a depolarizing response (67%), a hyperpolarizing response (20%) and a biphasic response consisting of a hyperpolarizing response followed by a depolarizing response (13%). Under voltage clamp control, the depolarizing response was observed as an inward current resulting from a decrease in conductance which was constant over the membrane potential range of -100 to -50 mV. Reversal potential was negative to -80 mV. An increase in the excitability of neurons (as measured by responses to identical intracellularly applied depolarizing current pulses) during the depolarizing responses was due to the increase in steady state inward current. When intracellular DC current of equal amplitude but opposite polarity was applied, no increase in excitability was observed. This response was always blocked by the addition of atropine (0.5-1 microM) to the perfusate. The hyperpolarizing response was observed as an increase in outward current due to an increase in conductance with marked voltage sensitivity (over the range of -100 to -50 mV) characteristic of the anomalous rectifier. Preliminary data indicated that the hyperpolarizing response was more sensitive to pirenzepine (complete blockade at 1.0 microM) than the depolarizing response (complete blockade at 2 microM) but neither response was affected by pirenzepine concentrations of 200 nM or less. Cholinergic effects on evoked depolarizing PSPs were examined on neurons with depolarizing (n = 3) and biphasic (n = 1) responses and in all cases, the PSPs were enhanced. This enhancement was blocked by atropine. In conclusion, it is suggested that activation of two different muscarinic receptors (neither of which is the M1 receptor) on mPRF neurons results in two different responses, a decrease in a voltage-insensitive potassium conductance and an increase in the anomalous rectifier.
|Original language||English (US)|
|Title of host publication||EXS|
|Number of pages||15|
|State||Published - 1989|
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