Auditory Sensory Gating in the Neonatal Ventral Hippocampal Lesion Model of Schizophrenia

Abstract

Background/Aims: The neonatal ventral hippocampal lesion (NVHL) rat model shows biological and behavioral abnormalities similar to schizophrenia. Disturbed sensory gating reflects a consistent neurobiological abnormality in schizophrenia. Although of critical interest, sensory gating has not been evaluated in the NVHL model. Methods: The N40 rat analog of the human P50 was measured to assess sensory response and gating in NVHL and sham rats. Epidural electrodes recorded evoked potentials (EPs), from which amplitudes, latencies, difference scores (S1–S2) and gating ratios (S2/S1) were assessed. Power and phase locking were computed for evoked EEG activity, to test for frequency-specific abnormalities. Results: Prolonged S1 N40 latency was detected in the NVHL group, but amplitude and power measures did not differ. NVHL rats demonstrated disturbed phase-locked sensory gating at theta and beta frequencies, as well as reduced phase-locked gamma activity across stimuli, most robustly at S1. Conclusions: While measures of sensory gating obtained from the EP were relatively insensitive to the NVHL model, phase locking across trials was affected. NVHL rats may have increased evoked response temporal variability, similar to patients with schizophrenia. This pattern of findings likely reflects core developmental NVHL disturbances in dorsal hippocampal circuits associated with temporal and frontal areas.

Sensory and Sensorimotor Gating Deficits after Neonatal Ventral Hippocampal Lesions in Rats

“…Our finding of reduced N40 gating in NVHL rats is somewhat supported by a previous study [36] that examined the complex oscillatory dynamics underlying sensory registration and gating indices. Although NVHL rats did not exhibit deficient S1 or S2 amplitudes or S2/S1 gating, significant S1 latency prolongation and marked disruptions in theta, beta, and gamma oscillations were observed [36], supporting the use of the NVHL for modeling neurophysiological abnormalities that are similar to those observed in schizophrenia patients.…”

“…Although NVHL rats did not exhibit deficient S1 or S2 amplitudes or S2/S1 gating, significant S1 latency prolongation and marked disruptions in theta, beta, and gamma oscillations were observed [36], supporting the use of the NVHL for modeling neurophysiological abnormalities that are similar to those observed in schizophrenia patients. …”

Reverse Translation of Clinical Electrophysiological Biomarkers in Behaving Rodents under Acute and Chronic NMDA Receptor Antagonism

“…EEG abnormalities are well characterized in schizophrenia (Cho et al, 2006;Hong et al, 2012;Rutter et al, 2009;Uhlhaas and Singer, 2010), bipolar disorder (Clementz et al, 1994), alcohol dependence (Costa and Bauer, 1997), and other psychiatric conditions. Previous studies have assessed EEG and evoked potentials in rodent models (Bickel et al, 2008;Broberg et al, 2010;Dissanayake et al, 2009;Ehrlichman et al, 2009b;Hakami et al, 2009;Vohs et al, 2009), and recent evidence suggests surface EEG is correlated with neural synchrony among local field potential (LFP) sites (Musall et al, 2014). However, the results are difficult to compare with human data due to very different approaches in how the signals are acquired and processed.…”

Phenomenological Dimensions of Sensory Gating

“…Subsequent studies have continued this line of investigation, not only replicating the findings at the phenomenological level of analysis [3][4][5][6] but also specifying candidate neurophysiological mechanisms to account for these anomalies. [7][8][9][10][11] Despite the impact of the article of McGhie and Chapman, 2 little has been done in the intervening decades to further characterize sensory gating at the phenomenological, or experiential, level of analysis. Instead, there have been tremendous advances in characterizing neurophysiological sensory gating deficits believed to produce the phenomenology McGhie and Chapman 2 characterized.…”