Delta oscillation and short-term plasticity in the rat medial prefrontal cortex: modelling NMDA hypofunction of schizophrenia

• Published in: The international journal of neuropsychopharmacology 2011-02, Vol.14 (1), p.29-42
• Main Authors: Kiss, Tamás, Hoffmann, William E., Hajós, Mihály
• Format: Article
• Language: English
• Subjects: Animals; Biphenyl Compounds - pharmacology; Delta Rhythm - drug effects; Disease Models, Animal; Dizocilpine Maleate - pharmacology; Electric Stimulation; Electroencephalography - drug effects; Excitatory Postsynaptic Potentials - drug effects; Hippocampus - drug effects; Hippocampus - physiopathology; Lidocaine - administration & dosage; Male; N-Methylaspartate - physiology; Neuronal Plasticity - drug effects; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Quinazolines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Schizophrenia - chemically induced; Schizophrenia - physiopathology; Sulfonamides - pharmacology; Synaptic Transmission - drug effects; Time Factors
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145710000271

Dysfunction of the prefrontal cortex (PFC) is considered to be an important factor contributing to a decrease in cognitive performance of schizophrenia patients. The medial PFC (mPFC) is innervated by the hippocampus/subiculum, and the subiculum–mPFC pathway is known to be involved in various cognitive processes. Glutamate-containing subicular axons innervate cortical pyramidal neurons and interneurons where AMPA and NMDA receptors are implicated in synaptic transmission. In our experiments, properties of subiculum–mPFC interactions were studied using pathway stimulation and local field potential (LFP) recordings of the mPFC in urethane-anaesthetized rats. Changes in paired-pulse facilitation (PPF) and LFP oscillations, effects of the NMDA receptor antagonist MK-801, and the AMPAkine LY451395 were evaluated. Effects of disruption of the thalamo-cortical loop with local microinjection of lidocaine into the mediodorsal thalamic nucleus (MD) were also studied. Our findings demonstrate that both systemic administration of MK-801 and local MD lidocaine microinjection produce similar changes in LFP oscillations and reduction in PPF. Specifically, it was observed that MK-801 (0.05 mg/kg i.v.) and intra-thalamic lidocaine changed regular, 2 Hz delta oscillation to a less regular 0.5–1.5 Hz delta rhythm. Concurrently, PPF in response to electrical stimulation of the subiculum was significantly attenuated. Administration of the AMPAkine LY451395 (0.01 mg/kg i.v.) reversed the MK-801- and lidocaine-induced changes, and was itself blocked by the AMPA receptor antagonist CP-465022. Analysis of our findings suggests a critical role of cortical interneurons in NMDA/AMPA receptor-mediated changes in thalamo-cortical oscillations and PPF, and contributes to our understanding of the NMDA hypofunction model of schizophrenia.