196: ABNORMAL FIRING PATTERNS IN THE THALAMIC RETICULAR NUCLEUS AFTER ASPHYXIAL CARDIAC ARREST

Abstract

Introduction: Cardiac arrest (CA) is a major cause of morbidity and mortality in children. Our prior studies have shown that CA disrupts neuronal circuitry in the somatosensory thalamus and have suggested that neurons in the thalamic Reticular Nucleus (RTn) are particularly sensitive to hypoxic-ischemic insult. RTn contains inhibitory interneurons that modulate attention, arousal and transfer of somatosensory information to the cerebral cortex. The specific impact of CA and resuscitation on the activity patterns of RTn neurons is unknown. Methods: We used a model of asphyxial CA in developing rats, followed by single neuron extracellular recordings in vivo. Post-natal day 19–21 Long-Evans rats were intubated and mechanically ventilated. Asphyxia was induced by discontinuing mechanical ventilation under neuromuscular blockade. After 9.5 minutes, rats (n=4) were resuscitated with mechanical ventilation, external chest compressions, epinephrine and sodium bicarbonate. A separate cohort of rats (n=4) received a sham intervention without asphyxia. Single neuron recordings were carried out after a 2–3 week survival period. Rats underwent a tracheostomy, arterial and venous line placement, and a craniotomy. Recordings were obtained under fentanyl analgesia and neuromuscular blockade. Electrodes were placed into RTn using a brain atlas and local topography. Spontaneous firing rates of individual RTn neurons were recorded and compared between sham and CA rats. Recording locations were confirmed with histology. Results: We recorded from 34 and 28 RTn neurons in CA and sham rats, respectively. RTn neurons in CA rats have lower spontaneous firing rates compared to sham rats (14.5 ± 1.45 vs 18.9 ± 1.97 Hz, p < 0.05). Furthermore, RTn neurons in CA rats have abnormal firing patterns as revealed by frequency of action potential bursts. Normal RTn neurons alternate between tonic and burst firing mode, reflecting and driving normal thalamic rhythms. In sham rats, RTn neurons fire 39.8 ± 8.50 bursts/min, and 22.6 ± 4.76 percent of all discharged action potentials are contained in bursts. In contrast, in CA rats, RTn neurons discharge 10.4 ± 4.29 bursts/min, and 5.09 ± 1.80 percent of discharged action potentials are contained in bursts. Hence, RTn neurons spend significantly less time in burst firing mode in CA compared to sham rats (p<0.05). Conclusions: Asphyxial CA results in decreased firing rates and abnormal firing dynamics in thalamic RTn neurons. RTn neurons regulate attention, arousal and sensory processing. Hence, abnormal network dynamics in the thalamus may contribute to neurologic deficits observed in CA survivors and may represent a novel therapeutic target.