Effects of restraint and haloperidol on sensory gating in the midbrain of awake rats

Abstract

Deficits in sensory processing have been reported to be associated with an array of neuropsychiatric disorders including schizophrenia. Auditory sensory gating paradigms have been routinely used to test the integrity of inhibitory circuits hypothesized to filter sensory information. Abnormal dopaminergic neurotransmission has been implicated in the expression of schizophrenic symptoms. The aim of this study was to determine if inhibitory gating in response to paired auditory stimuli would occur in putative dopaminergic and non-dopaminergic midbrain neurons. A further goal of this study was to determine if restraint, a classic model of stress known to increase extracellular dopamine levels, and systemic haloperidol injections affected inhibitory mechanisms involved in sensory gating. Neural activity in the rat midbrain was recorded across paired auditory stimuli (first auditory stimulus (S1) and second auditory stimulus (S2)) under resting conditions, during restraint and after systemic haloperidol injections. Under resting conditions, a subset of putative GABA neurons showed fast, gated, short latency responses while putative dopamine neurons showed long, slow responses that were inhibitory and ungated. During restraint, gated responses in putative GABAergic neurons were decreased (increased S2/S1 or ratio of test to conditioning (T/C)) by reducing the response amplitude to S1. Systemic haloperidol decreased the T/C ratio by preferentially increasing response amplitude to S1. The results from this study suggest that individual neurons encode discrete components of the auditory sensory gating paradigm, that phasic midbrain GABAergic responses to S1 may trigger subsequent inhibitory filtering processes, and that these GABAergic responses are sensitive to restraint and systemic haloperidol.