Strychnine-sensitive glycine receptors (GlyR) play a major role in the excitability of CNS neurons and are also a major target of many drugs including some general anesthetics and ethanol. The prefrontal cortex (PFC) is an important substrate responsible for cognitive function and for sedation, as well as hypnosis (unconsciousness) which is induced by general anesthetics and ethanol. However, the functions and the physiological and pharmacological properties of GlyRs in mature PFC neurons have not been well studied. In this study, whole-cell currents induced by glycine (I(Gly)) were recorded from freshly isolated PFC neurons of Sprague-Dawley rats aged 5 to 39 postnatal days (neonatal, P5-12; weanling, P17-21 and peri-adolescent, P30-39). We found that most of the neurons examined were responsive to glycine and the response was concentration dependent. With the increase of age, the sensitivity to glycine was significantly decreased and the sensitivity to picrotoxin was significantly increased. Conversely, the changes in sensitivity to strychnine were not significant. Interestingly, I(Gly) of all age groups was suppressed (to different scope) by low concentrations of picrotoxin (≤ 30 μM), which selectively blocked α homomeric GlyRs. Conversely, about 20-65% of I(Gly) remained in the presence of 300 μM picrotoxin, suggesting the picrotoxin-resistant subtype the αβ heteromeric GlyR, was also present. These data provide the first evidence that there are at least two subtypes of functional GlyRs in the PFC neurons of young rats, and their physiological and pharmacological properties change substantially during maturation.
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