ABSTRACT
Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
Subject(s)
Association Learning/physiology , Brain Waves/physiology , GABAergic Neurons/physiology , Interneurons/physiology , Memory, Short-Term/physiology , Receptors, N-Methyl-D-Aspartate/physiology , Animals , Association Learning/drug effects , Brain Waves/drug effects , Conditioning, Psychological/drug effects , Conditioning, Psychological/physiology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GABA Antagonists/pharmacology , GABAergic Neurons/metabolism , Interneurons/drug effects , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory, Short-Term/drug effects , Mice , Mice, Transgenic , Parvalbumins/metabolism , Photic Stimulation/methods , Picrotoxin/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/genetics , Sensory Gating/drug effects , Sensory Gating/physiology , Stereotyped Behavior/drug effects , Stereotyped Behavior/physiologySubject(s)
Androstadienes/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Asthma/blood , Administration, Inhalation , Androstadienes/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Asthma/drug therapy , Dose-Response Relationship, Drug , Fluticasone , Humans , Lung Volume MeasurementsABSTRACT
Several new techniques have been introduced for use in the esthetic restoration of posterior cavities to substitute for the presumed toxicity of amalgam. Composite-laminated glass-ionomer cement restorations, the sandwich technique, have been recommended for caries-risk patients. Clinical evaluation of the use of conventional glass-ionomer cements in the open-sandwich restoration has shown a high failure rate. The aim of this study was to evaluate the durability and cariostatic effect of a modified open-sandwich restoration utilizing a resin-modified glass-ionomer cement (RMGIC) in large cavities. The materials consisted of 274 mostly extensive Class II Vitremer/Z100 restorations performed by four dentists in 168 adults. Six experimental groups were investigated. In four groups a thick and in two groups a thin layer of cement was placed. Cavity conditioning before application of the RMGIC self-etching primer was done in 3 groups with polyacrylic acid and in one group with maleic acid; in two groups, only water rinsing was performed. The restorations were evaluated at baseline and after 6, 12, 24, and 36 months according to modified USPHS criteria (van Dijken, 1986). After 3 years, 239 restorations were evaluated. Twelve (5%) were estimated as non-acceptable. Two were replaced, and seven were repaired with resin composite. Tooth fractures were observed in 2.5%. Slight erosion of the RMGIC part was seen in 4%, and in one case operative treatment was indicated. Post-operative sensitivity was reported for 9 teeth. Forty-three percent of the patients were considered as caries-risk patients. Only one restoration showed secondary caries. The three-year results indicated that the modified open-sandwich restoration is an appropriate alternative to amalgam including extensive restorations.