Alterations in the intrinsic burst activity of Purkinje neurons in offspring maternally exposed to the CB1 cannabinoid agonist WIN 55212-2.

Burst firing plays an important role in normal neuronal function and dysfunction. In Purkinje neurons, where the firing rate and discharge pattern encode the timing signals necessary for motor function, any alteration in firing properties, including burst activity, may affect the motor output. Therefore, we examined whether maternal exposure to the cannabinoid receptor agonist WIN 55212-2 (WIN) may affect the burst firing properties of cerebellar Purkinje cells in offspring. Whole-cell somatic patch-clamp recordings were made from cerebellar slices of adult male rats that were exposed to WIN prenatally. WIN exposure during pregnancy induced long-term alterations in the burst firing behavior of Purkinje neurons in rat offspring as evidenced by a significant increase in the mean number of spikes per burst (p < 0.05) and the prolongation of burst firing activity (p < 0.01). The postburst afterhyperpolarization potential (p < 0.001), the mean intraburst interspike intervals (p < 0.001) and the mean intraburst firing frequency (p < 0.001) were also significantly increased in the WIN-treated group. Prenatal exposure to WIN enhanced the firing irregularity as reflected by a significant decrease in the coefficient of variation of the intraburst interspike interval (p < 0.05). Furthermore, whole-cell voltage-clamp recordings revealed that prenatal WIN exposure significantly enhanced Ca(2+) channel current amplitude in offspring Purkinje neurons compared to control cells. Overall, the data presented here strongly suggest that maternal exposure to cannabinoids can induce long-term changes in complex spike burst activity, which in turn may lead to alterations in neuronal output.