Neonatal ketamine exposure causes impairment of long-term synaptic plasticity in the anterior cingulate cortex of rats. 2014

R-R Wang, and J-H Jin, and A W Womack, and D Lyu, and S S Kokane, and N Tang, and X Zou, and Q Lin, and J Chen
Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing, China; Department of Psychology, College of Science, The University of Texas at Arlington, Arlington, TX, USA; Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Ketamine, a dissociative anesthetic most commonly used in many pediatric procedures, has been reported in many animal studies to cause widespread neuroapoptosis in the neonatal brain after exposure in high doses and/or for a prolonged period. This neurodegenerative change occurs most severely in the forebrain including the anterior cingulate cortex (ACC) that is an important brain structure for mediating a variety of cognitive functions. However, it is still unknown whether such apoptotic neurodegeneration early in life would subsequently impair the synaptic plasticity of the ACC later in life. In this study, we performed whole-cell patch-clamp recordings from the ACC brain slices of young adult rats to examine any alterations in long-term synaptic plasticity caused by neonatal ketamine exposure. Ketamine was administered at postnatal day 4-7 (subcutaneous injections, 20mg/kg given six times, once every 2h). At 3-4weeks of age, long-term potentiation (LTP) was induced and recorded by monitoring excitatory postsynaptic currents from ACC slices. We found that the induction of LTP in the ACC was significantly reduced when compared to the control group. The LTP impairment was accompanied by an increase in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated excitatory synaptic transmission and a decrease in GABA inhibitory synaptic transmission in neurons of the ACC. Thus, our present findings show that neonatal ketamine exposure causes a significant LTP impairment in the ACC. We suggest that the imbalanced synaptic transmission is likely to contribute to ketamine-induced LTP impairment in the ACC.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D008297 Male Males
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009473 Neuronal Plasticity The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations. Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D005260 Female Females
D006179 Gyrus Cinguli One of the convolutions on the medial surface of the CEREBRAL HEMISPHERES. It surrounds the rostral part of the brain and CORPUS CALLOSUM and forms part of the LIMBIC SYSTEM. Anterior Cingulate Gyrus,Brodmann Area 23,Brodmann Area 24,Brodmann Area 26,Brodmann Area 29,Brodmann Area 30,Brodmann Area 31,Brodmann Area 32,Brodmann Area 33,Brodmann's Area 23,Brodmann's Area 24,Brodmann's Area 26,Brodmann's Area 29,Brodmann's Area 30,Brodmann's Area 31,Brodmann's Area 32,Brodmann's Area 33,Cingulate Gyrus,Gyrus Cinguli Anterior,Retrosplenial Complex,Retrosplenial Cortex,Anterior Cingulate,Anterior Cingulate Cortex,Cingular Gyrus,Cingulate Area,Cingulate Body,Cingulate Cortex,Cingulate Region,Gyrus, Cingulate,Posterior Cingulate,Posterior Cingulate Cortex,Posterior Cingulate Gyri,Posterior Cingulate Gyrus,Posterior Cingulate Region,Superior Mesial Regions,24, Brodmann Area,Anterior Cingulate Cortices,Anterior Cingulates,Anterior, Gyrus Cinguli,Anteriors, Gyrus Cinguli,Area 23, Brodmann,Area 23, Brodmann's,Area 24, Brodmann,Area 24, Brodmann's,Area 26, Brodmann,Area 26, Brodmann's,Area 29, Brodmann,Area 29, Brodmann's,Area 30, Brodmann,Area 30, Brodmann's,Area 31, Brodmann,Area 31, Brodmann's,Area 32, Brodmann,Area 32, Brodmann's,Area 33, Brodmann,Area 33, Brodmann's,Area, Cingulate,Body, Cingulate,Brodmanns Area 23,Brodmanns Area 24,Brodmanns Area 26,Brodmanns Area 29,Brodmanns Area 30,Brodmanns Area 31,Brodmanns Area 32,Brodmanns Area 33,Cingulate Areas,Cingulate Bodies,Cingulate Cortex, Anterior,Cingulate Cortex, Posterior,Cingulate Gyrus, Anterior,Cingulate Gyrus, Posterior,Cingulate Region, Posterior,Cingulate Regions,Cingulate, Anterior,Cingulate, Posterior,Cinguli Anterior, Gyrus,Cinguli Anteriors, Gyrus,Complex, Retrosplenial,Cortex, Anterior Cingulate,Cortex, Cingulate,Cortex, Posterior Cingulate,Cortex, Retrosplenial,Gyrus Cinguli Anteriors,Gyrus, Anterior Cingulate,Gyrus, Cingular,Gyrus, Posterior Cingulate,Posterior Cingulate Cortices,Posterior Cingulate Regions,Posterior Cingulates,Region, Cingulate,Region, Posterior Cingulate,Retrosplenial Complices,Retrosplenial Cortices,Superior Mesial Region
D000778 Anesthetics, Dissociative Intravenous anesthetics that induce a state of sedation, immobility, amnesia, and marked analgesia. Subjects may experience a strong feeling of dissociation from the environment. The condition produced is similar to NEUROLEPTANALGESIA, but is brought about by the administration of a single drug. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Dissociative Anesthetics
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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