Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

Authors

Jennifer L. Zick, University of Minnesota - Twin Cities
Rachael K. Blackman, University of Minnesota - Twin Cities
David A. Crowe, Augsburg UniversityFollow
Bagrat Amirikian, University of Minnesota - Twin Cities
Adele L. DeNicola, University of Minnesota - Twin Cities
Theoden I. Netoff, University of Minnesota - Twin Cities
Matthew V. Chafee, University of Minnesota - Twin Cities

Document Type

Article

Publication Date

6-27-2018

DOI

10.1016/j.neuron.2018.05.010

Abstract

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity might be interrelated factors in pathogenesis, supporting an activity-dependent disconnection theory of schizophrenia. In this theory, disruption of NMDAR synaptic function leads to dys-regulated timing of action potentials in prefrontal networks, accelerating synaptic disconnection through a spike-timing-dependent mechanism.

Comments

Published in final edited form as: Neuron. 2018 June 27; 98(6): 1243–1255.e5. doi:10.1016/j.neuron.2018.05.010.

Recommended Citation

Zick, J. L., Blackman, R. K., Crowe, D. A., Amirikian, B., DeNicola, A. L., Netoff, T. I., & Chafee, M. V. (2018). Blocking NMDAR disrupts spike timing and decouples monkey prefrontal circuits: Implications for activity-dependent disconnection in schizophrenia. Neuron, 98(6), 1243-1255.