Inhibition of long-term potentiation development in rat hippocampal slice by alpha 2-macroglobulin, an acute-phase protein in the brain.
alpha-Macroglobulins/*pharmacology; Animals; Electric Stimulation; Hippocampus/drug effects/*physiology; Humans; In Vitro Techniques; Long-Term Potentiation/*drug effects; Methylamines/pharmacology; Neurites/drug effects/*physiology; Pyramidal Cells/drug effects/physiology; Rats; Synapses/drug effects/physiology; Synaptic Transmission/drug effects; Time Factors
Alpha-2-macroglobulin (alpha 2M) in the rat and human brain is an acute-phase protein synthesized primarily by astrocytes, and it has been implicated in Alzheimer's disease and other neuropathological processes. The activated forms of alpha 2M, but not the native form, can suppress the neurite outgrowth of the central neurons, presumably through binding to neurotrophic factors and through direct inhibition of neurotrophic factor receptor signal transduction. Since neurotrophic factors are known to be involved in synaptic plasticity, we tested the effect of both the native and methylamine-activated (MA-alpha 2M) forms of alpha 2M on long-term potentiation (LTP) in area CA1 of adult rat hippocampal slice. Neither native alpha 2M nor MA-alpha 2M had an effect on baseline synaptic transmission. LTP induced by 200-Hz trains in the presence of 1.4 microM or 0.14 microM native alpha 2M was indistinguishable from control LTP. Although the presence of MA-alpha 2M at the same concentrations did not interfere with LTP induction, the development and maintenance of potentiation was blocked in a concentration-dependent time course. Results of this study indicate that the accumulation and activation of alpha 2M with inflammatory neuropathologies such as Alzheimer's disease can inhibit synaptic plasticity, which might partly account for the memory deficits seen in these patients.
Cavus I; Koo P H; Teyler T J
Journal of neuroscience research
1996
1996-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/(SICI)1097-4547(19960201)43:3%3C282::AID-JNR3%3E3.0.CO;2-F" target="_blank" rel="noreferrer noopener">10.1002/(SICI)1097-4547(19960201)43:3%3C282::AID-JNR3%3E3.0.CO;2-F</a>
Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.
2-Amino-5-phosphonovalerate/pharmacology; Animals; Bicuculline/analogs & derivatives/pharmacology; Chlorides/pharmacology; Dendrites/drug effects/*physiology; Evoked Potentials/drug effects; GABA-A Receptor Antagonists; GABA-A/drug effects/*physiology; Hippocampus/*physiology; In Vitro Techniques; Kinetics; Mathematics; Membrane Potentials/drug effects; Models; Neurological; Neurons/drug effects/*physiology; Organophosphorus Compounds/pharmacology; Pyramidal Tracts/drug effects/*physiology; Quinoxalines/pharmacology; Rats; Receptors; Synapses/drug effects/physiology
1. gamma-Aminobutyric acidA (GABAA) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABAA and late, GABAB receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB receptor antagonist
Lambert N A; Borroni A M; Grover L M; Teyler T J
Journal of neurophysiology
1991
1991-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jn.1991.66.5.1538" target="_blank" rel="noreferrer noopener">10.1152/jn.1991.66.5.1538</a>
GABAa receptor-mediated field potentials are enhanced in area CA1 following prenatal cocaine exposure.
*Prenatal Exposure Delayed Effects; AMPA/physiology; Animals; Bicuculline/analogs & derivatives/pharmacology; Cocaine/*pharmacology; Female; GABA-A/*physiology; GABA-B/physiology; Hippocampus/drug effects/*physiology; In Vitro Techniques; Membrane Potentials/drug effects/physiology; N-Methyl-D-Aspartate/physiology; Pregnancy; Quinoxalines/pharmacology; Rabbits; Receptors; Synapses/drug effects/physiology
Prenatal cocaine exposure results in several documented changes in neurotransmitter receptor number and structure. Increases have been reported for cortical catecholamine and indoleamine receptor number and binding affinity, in the subunit expression of glutamatergic NMDA and AMPA receptors in the striatum, and in GABA immunoreactivity in the anterior cingulate cortex. We sought information on the functional consequences of cocaine-induced alterations in receptor structure/number. Since hippocampal amino acid neurotransmitters are of critical importance and have been shown to be affected by cocaine, we studied field potentials produced by synaptic activation of isolated glutamatergic NMDA and AMPA receptors and GABAa and GABAb responsive receptors in area CA1 of rabbit hippocampal slices. We found the GABAa receptor population produced significantly larger field potentials in cocaine-exposed offspring compared to controls, while other receptors produced responses similar to controls.
Little J Z; Teyler T J
Brain research. Developmental brain research
1998
1998-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0165-3806(98)00100-x" target="_blank" rel="noreferrer noopener">10.1016/s0165-3806(98)00100-x</a>