title: Auditory steady state responses in a schizophrenia rat model probed by excitatory/inhibitory receptor manipulation.
abstract: Alterations in neural synchrony and oscillations may contribute to the pathophysiology of schizophrenia and reflect aberrations in cortical glutamatergic and GABAergic neurotransmission. We tested the effects of a GABA agonist and an NMDA antagonist on auditory steady state responses (ASSRs) in awake rats with neonatal ventral hippocampal lesions (NVHLs) as a neurodevelopmental model of schizophrenia. NVHL vs. SHAM lesioned rats were injected with saline then either ketamine (NMDA antagonist) or muscimol (GABA(A) agonist). Time-frequency analyses examined alterations in phase locking (consistency) across trials and changes in total power (magnitude). ASSRs were compared at five stimulation frequencies (10, 20, 30, 40, and 50 Hz). In SHAM rats, phase locking and power generally increased with stimulation frequency. Both ketamine and muscimol also increased phase locking and power in SHAM rats, but mostly in the 20 to 40 Hz range. NVHL and ketamine altered the frequency dependence of phase locking, while only ketamine changed power frequency dependence. Muscimol affected power, but not phase locking, in the NVHL rats. NVHL and ketamine models of schizophrenia produce similar independent effects on ASSR, potentially representing similar forms of cortical network/glutamatergic dysfunction, albeit the effects of ketamine were more robust. Muscimol produced NVHL-dependent reductions in ASSR measures, suggesting that cortical networks in this model are intolerant to post-synaptic GABAergic stimulation. These findings suggest the utility of combining lesion, pharmacological, and ASSR approaches in understanding neural mechanisms underlying disturbed synchrony in schizophrenia.
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, 1111 W. 10th St. Indianapolis, IN 46202, USA. jvohs@iupui.edu
authors.forename: Jenifer L
authors.initials: JL
authors.lastname: Vohs
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Chambers
authors.forename: Brian F
authors.initials: BF
authors.lastname: O'Donnell
authors.forename: Giri P
authors.initials: GP
authors.lastname: Krishnan
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Morzorati
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists