Hypoxia Depresses Synaptic Transmission in the Primary Motor Cortex of the Infant Rat-Role of Adenosine A1 Receptors and Nitric Oxide.

Abstract

The acute and long-term consequences of perinatal asphyxia have been extensively investigated, but only a few studies have focused on postnatal asphyxia. In particular, electrophysiological changes induced in the motor cortex by postnatal asphyxia have not been examined so far, despite the critical involvement of this cortical area in epilepsy. In this study, we exposed primary motor cortex slices obtained from infant rats in an age window (16-18 day-old) characterized by high incidence of hypoxia-induced seizures associated with epileptiform motor behavior to 10 min of hypoxia. Extracellular field potentials evoked by horizontal pathway stimulation were recorded in layers II/III of the primary motor cortex before, during, and after the hypoxic event. The results show that hypoxia reversibly depressed glutamatergic synaptic transmission and neuronal excitability. Data obtained in the presence of specific blockers suggest that synaptic depression was mediated by adenosine acting on pre-synaptic A1 receptors to decrease glutamate release, and by a nitric oxide (NO)/cGMP postsynaptic pathway. These effects are neuroprotective because they limit energy failure. The present findings may be helpful in the preclinical search for therapeutic strategies aimed at preventing acute and long-term neurological consequences of postnatal asphyxia.