PT - JOURNAL ARTICLE AU - Jason W. Middleton AU - Daniel J. Simons AU - Jennifer W. Simmons AU - Robert S.B. Clark AU - Patrick M. Kochanek AU - Michael Shoykhet TI - Long-Term Deficits in Cortical Circuit Function after Asphyxial Cardiac Arrest and Resuscitation in Developing Rats AID - 10.1523/ENEURO.0319-16.2017 DP - 2017 Jun 19 TA - eneuro PG - ENEURO.0319-16.2017 4099 - http://www.eneuro.org/content/early/2017/06/19/ENEURO.0319-16.2017.short 4100 - http://www.eneuro.org/content/early/2017/06/19/ENEURO.0319-16.2017.full AB - Cardiac arrest is a common cause of global hypoxic-ischemic brain injury. Poor neurologic outcome among cardiac arrest survivors results not only from direct cellular injury but also from subsequent long-term dysfunction of neuronal circuits. Here, we investigated the long-term impact of cardiac arrest during development on the function of cortical Layer IV (L4) barrel circuits in the rat primary somatosensory cortex. We used multi-electrode single neuron recordings to examine responses of presumed excitatory L4 barrel neurons to controlled whisker stimuli in adult (8 ± 2 mo old) rats that had undergone 9 min of asphyxial cardiac arrest and resuscitation during the 3rd postnatal week. Results indicate that responses to topographically appropriate "principal" whisker (PW) deflections are smaller in magnitude in cardiac arrest survivors than in control rats. Responses to adjacent whisker (AW) deflections are similar in magnitude between the two groups. Due to a disproportionate decrease in PW-evoked responses, receptive fields of L4 barrel neurons are less spatially focused in cardiac arrest survivors than in control rats. In addition, spiking activity among L4 barrel neurons is more correlated in cardiac arrest survivors than in controls. Computational modeling demonstrates that experimentally-observed disruptions in barrel circuit function after cardiac arrest can emerge from a balanced increase in background excitatory and inhibitory conductances in L4 neurons. Experimental and modeling data together suggest that after a hypoxic-ischemic insult, cortical sensory circuits are less responsive and less spatially tuned. Modulation of these deficits may represent a therapeutic approach to improving neurologic outcome after cardiac arrest.Significance Statement Cardiac arrest survivors often suffer severe neurologic injury. Neurologic injury and subsequent behavioral deficits likely arise not only from arrest-related cell death but also from long-term dysfunction of neuronal circuits. We show in a rat model of pediatric asphyxial cardiac arrest that deficits in sensory information processing persist in cortical Layer IV circuits for months after injury. As a general feature, hypoxic-ischemic brain injury leads to less responsive and less spatially tuned sensory cortical circuits. Understanding mechanisms underlying abnormal circuit function after cardiac arrest may lead to new approaches for modulating neuronal circuits and restoring normal function in survivors.