Title

NEUROPHYSIOLOGY OF AUDITORY INHIBITORY GATING IN RAT MEDIAL PREFRONTAL CORTEX

Date of Award

2006

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Psychology/Experimental

First Advisor

Howard Cromwell

Abstract

Medial prefrontal cortex (mPFC) is a crucial region involved in inhibitory processes. Damage to mPFC leads to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The present study was designed to examine basic properties, influence of aversive conditioning, and neuropharmacology of inhibitory gating in mPFC. Inhibitory gating is a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e., in schizophrenia, PTSD, and drug abuse). In the present research, single-units and local field potentials (LFPs) were measured using chronic microwire arrays implanted in rat mPFC. The stability of gating was first examined using paired tone tests in short-term (within session) and long-term (between session) analyses of auditory gating. LFPs displayed reduction in amplitudes of tone responses and increase of gating over both short and long-term time windows. A variety of single-unit responses retained similar levels of auditory responsiveness and inhibition in both short and long-term analysis. Next, altering the interval between tones in each tone-pair influenced the potency of inhibition. Neural inhibition decreased monotonically related to the increase in intertone interval for both LFPs and single-units. The influence of fear conditioning was investigated by administering 30 footshock pairings with tones similar to those normally used to test gating. Inhibitory gating of LFPs weakened, and animals’ orienting behavior to tones increased after, compared to before, the session of footshock and tone pairings. Systemic neuropharmacological manipulations were used to investigate effects of dopamine and GABA neurotransmitter systems on inhibitory gating of LFPs in mPFC. For effects of dopaminergic manipulations, the drugs haloperidol and apomorphine respectively strengthened and nearly eliminated inhibitory gating, and the drugs had completely opposite effects of respectively decreasing and increasing evoked response to the first tone. For effects of GABA manipulations, the drugs baclofen and pentobarbital strengthened gating to varying degrees. This set of experiments lays essential framework for investigation of inhibitory gating in mPFC and the network of connected brain structures that also display inhibitory gating.