Disruption of medial prefrontal synchrony in the subchronic phencyclidine model of schizophrenia in rats.
Bottom Line: We found that this regimen reduced theta oscillations in the medial prefrontal cortex.It further produced abnormal cortical synchronization in putative cortical pyramidal cells.These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks.
Affiliation: School of Psychology, College of Medicine, Biological Sciences and Psychology, University of Leicester, United Kingdom.Show MeSH
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Mentions: The reduction in theta power suggested deficits in mPFC synchrony. To further investigate this observation we analyzed synchrony looking at both single-unit activity and spike-LFP locking. We analyzed 29 units in PCP-treated animals and 48 units in drug-naïve controls. In order to target putative pyramidal cells we recorded from units with relatively low firing rates. Firing rates did not differ significantly across the two groups: 0.90 Hz for saline (SEM = 0.48) and 1.12 for PCP (SEM = 0.51) and are consistent with the cells being regularly spiking units. To confirm this we calculated waveform shapes and these are largely consistent with previous work [e.g. (Bruno and Simons, 2002); initial wave duration (mean ± sd) was 0.64 ± 0.3036 ms and the second phase (corresponding to spike after-hyperpolarization) was 0.87 ± 0.34 ms]. To investigate spike synchrony we computed the cross-correlogram of spikes recorded simultaneously and calculated the area under the cross-correlogram integrating over windows of varying length (Fig. 2A). The area under the cross correlogram was significantly higher (95% bootstrapped confidence intervals) in PCP pre-treated animals over a range of window durations suggesting increased synchrony (Fig. 2B). To rule out the possibility that cluster cutting may influence this conclusion we calculated average auto-correlograms for PCP and vehicle-pretreated groups; the autocorrelograms did not differ significantly between conditions. During slow wave sleep, quiet wakefulness, and some forms of anesthesia including urethane, brain states are characterized by low-frequency, large-amplitude membrane potential changes (Steriade et al., 1993; Petersen et al., 2003). Here we found no difference in overall slow oscillation activity (<3.5 Hz) as a result of PCP treatment (Fig. 1). Still to rule out the possibility that spike cross correlations may be differentially affected by these so-called UP and DOWN states in the drugs vs. vehicle group we calculated the instantaneous oscillation phase of each spike using a Hilbert transformation of the low-pass (<3 Hz) filtered LFP trace to find spike occurrences during UP and DOWN states. Integrated averages of cross-correlations calculated from spike pairs occurring in either UP or DOWN states produced similar drug differences. Therefore we conclude that urethane-produced slow oscillations are unlikely to account for enhanced spike synchrony in PCP-treated animals.
Affiliation: School of Psychology, College of Medicine, Biological Sciences and Psychology, University of Leicester, United Kingdom.