Scholars@Duke
J. Victor Nadler

J. Victor Nadler

Professor Emeritus of Pharmacology & Cancer Biology
Pharmacology & Cancer Biology
nadle002@acpub.duke.edu
Duke Box 3813, Durham, NC 27710
308 Research Drive, Durham, NC 27710

Scholarly Works - Journal articles

Mechanisms of increased hippocampal excitability in the Mashl+/- mouse model of Na+ /K+ -ATPase dysfunction.

Journal article Epilepsia · July 2018 OBJECTIVE: Na+ /K+ -ATPase dysfunction, primary (mutation) or secondary (energy crisis, neurodegenerative disease) increases neuronal excitability in the brain. To evaluate the mechanisms underlying such increased excitability we studied mice carrying the ... Full text Link to item Cite

Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models.

Journal article Sci Data · May 9, 2017 Global expression profiling of neurologic or psychiatric disorders has been confounded by variability among laboratories, animal models, tissues sampled, and experimental platforms, with the result being that few genes demonstrate consistent expression cha ... Full text Open Access Link to item Cite

Persistent Hyperactivity of Hippocampal Dentate Interneurons After a Silent Period in the Rat Pilocarpine Model of Epilepsy.

Journal article Front Cell Neurosci · 2016 Profile of GABAergic interneuron activity after pilocarpine-induced status epilepticus (SE) was examined in the rat hippocampal dentate gyrus by analyzing immediate early gene expression and recording spontaneous firing at near resting membrane potential ( ... Full text Link to item Cite

What is a seizure focus?

Journal article Adv Exp Med Biol · 2014 The seizure focus is the site in the brain from which the seizure originated and is most likely equivalent to the epileptogenic zone, defined as the area of cerebral cortex indispensable for the generation of clinical seizures. The boundaries of this regio ... Full text Link to item Cite

Morphologic integration of hilar ectopic granule cells into dentate gyrus circuitry in the pilocarpine model of temporal lobe epilepsy.

Journal article J Comp Neurol · August 1, 2011 After pilocarpine-induced status epilepticus, many granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) are hyperexcitable and may therefore increase circuit excitability. This s ... Full text Link to item Cite

Aspartate release and signalling in the hippocampus.

Journal article Neurochem Res · April 2011 The Ca(2+)-dependent release of aspartate from hippocampal preparations was first reported 35 years ago, but the functional significance of this process remains uncertain. Aspartate satisfies all the criteria normally required for identification of a CNS t ... Full text Link to item Cite

Plasticity of glutamate synaptic mechanisms

Journal article Epilepsia · December 1, 2010 Enhanced glutamate synaptic transmission may be expected to alter the balance of excitation and inhibition in brain, leading to seizures. Several differences between epileptic and nonepileptic brains in presynaptic and postsynaptic glutamate mechanisms hav ... Full text Cite

Seizure-induced basal dendrites on granule cells

Journal article Epilepsia · December 1, 2010 Seizure-induced hilar basal dendrites on dentate granule cells are observed in several rodent models of temporal lobe epilepsy. Ultrastructural evidence showed that basal dendrites receive predominantly excitatory synapses, including many from mossy fibers ... Full text Cite

High ratio of synaptic excitation to synaptic inhibition in hilar ectopic granule cells of pilocarpine-treated rats.

Journal article J Neurophysiol · December 2010 After experimental status epilepticus, many dentate granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) have also been found in persons with epilepsy. These cells exhibit a high ... Full text Link to item Cite

Postsynaptic response to stimulation of the Schaffer collaterals with properties similar to those of synaptosomal aspartate release.

Journal article Brain Res · October 27, 2009 Aspartate satisfies all the criteria normally required for identification of a CNS neurotransmitter. Nevertheless, little electrophysiological evidence supports the existence of aspartate transmission. In studies with rat hippocampal synaptosomes, chemical ... Full text Link to item Cite

Enhanced tonic GABA current in normotopic and hilar ectopic dentate granule cells after pilocarpine-induced status epilepticus.

Journal article J Neurophysiol · August 2009 In temporal lobe epilepsy, loss of inhibitory neurons and circuit changes in the dentate gyrus promote hyperexcitability. This hyperexcitability is compensated to the point that dentate granule cells exhibit normal or even subnormal excitability under some ... Full text Link to item Cite

Impaired firing and sodium channel function in CA1 hippocampal interneurons after transient cerebral ischemia.

Journal article J Cereb Blood Flow Metab · August 2007 Although interneurons in area CA1 of the hippocampus are less vulnerable to cerebral ischemia than CA1 pyramidal cells, it is not clear whether their relatively intact cellular morphology implies preservation of normal function. As maintenance of cellular ... Full text Link to item Cite

Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy: correlation of cell loss with mossy fiber sprouting.

Journal article Exp Neurol · June 2007 Mossy fiber sprouting and the genesis of ectopic granule cells contribute to reverberating excitation in the dentate gyrus of epileptic brain. This study determined whether the extent of sprouting after status epilepticus in rats correlates with the seizur ... Full text Link to item Cite

Reduced aspartate release from rat hippocampal synaptosomes loaded with Clostridial toxin light chain by electroporation: evidence for an exocytotic mechanism.

Journal article Neurosci Lett · February 2, 2007 Featured Publication Aspartate can be released from certain hippocampal pathways along with glutamate or GABA. Although aspartate immunoreactivity has been localized to synaptic vesicles and aspartate release is Ca(2+)-dependent, there has been no clear evidence favoring an ex ... Full text Link to item Cite

Neuropeptide Y in the recurrent mossy fiber pathway.

Journal article Peptides · February 2007 Featured Publication In the epileptic brain, hippocampal dentate granule cells become synaptically interconnected through the sprouting of mossy fibers. This new circuitry is expected to facilitate epileptiform discharge. Prolonged seizures induce the long-lasting neoexpressio ... Full text Link to item Cite

Excitatory Amino Acids

Journal article · January 1, 2007 Glutamate is the predominant excitatory transmitter in the mammalian central nervous system. Glutamate plays a key role in pathways known or suspected to be involved in neuropsychiatric and neurodegenerative diseases. Thus, drugs directed at glutamate mech ... Full text Cite

Neuropeptide Y regulates recurrent mossy fiber synaptic transmission less effectively in mice than in rats: Correlation with Y2 receptor plasticity.

Journal article Neuroscience · December 28, 2006 A unique feature of temporal lobe epilepsy is the formation of recurrent excitatory connections among granule cells of the dentate gyrus as a result of mossy fiber sprouting. This novel circuit contributes to a reduced threshold for granule cell synchroniz ... Full text Link to item Cite

Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy.

Journal article Brain Res · March 17, 2006 Recurrent mossy fiber synapses in the dentate gyrus of epileptic brain facilitate the synchronous firing of granule cells and may promote seizure propagation. Mossy fiber terminals contain and release zinc. Released zinc inhibits the activation of NMDA rec ... Full text Link to item Cite

Depressed responses to applied and synaptically-released GABA in CA1 pyramidal cells, but not in CA1 interneurons, after transient forebrain ischemia.

Journal article J Cereb Blood Flow Metab · January 2006 Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas most CA1 interneurons survive. It has been proposed that calcium-binding proteins, neurotrophins, and/or inhibitory neuropeptides protect interneurons from ischemia. However, ... Full text Link to item Cite

Spontaneous release of neuropeptide Y tonically inhibits recurrent mossy fiber synaptic transmission in epileptic brain.

Journal article J Neurosci · February 16, 2005 Featured Publication In the pilocarpine model of temporal lobe epilepsy, mossy fibers coexpress the inhibitory transmitter neuropeptide Y (NPY) with glutamate. The effects of endogenous and applied NPY on recurrent mossy fiber synaptic transmission were investigated with the u ... Full text Link to item Cite

Aspartate release from rat hippocampal synaptosomes.

Journal article Neuroscience · 2004 Featured Publication Certain excitatory pathways in the rat hippocampus can release aspartate along with glutamate. This study utilized rat hippocampal synaptosomes to characterize the mechanism of aspartate release and to compare it with glutamate release. Releases of asparta ... Full text Link to item Cite

The recurrent mossy fiber pathway of the epileptic brain.

Journal article Neurochem Res · November 2003 Featured Publication The dentate gyrus is believed to play a key role in the pathogenesis of temporal lobe epilepsy. In normal brain the dentate granule cells serve as a high-resistance gate or filter, inhibiting the propagation of seizures from the entorhinal cortex to the hi ... Full text Link to item Cite

Short-term frequency-dependent plasticity at recurrent mossy fiber synapses of the epileptic brain.

Journal article J Neurosci · June 15, 2003 Featured Publication The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in human temporal lobe epilepsy and in animal models of this disorder, creating monosynaptic connections among granule cells. This novel granule cell network can support reverberat ... Full text Link to item Cite

Quantitative and morphological analysis of dentate granule cells with recurrent basal dendrites from normal and epileptic rats.

Journal article Hippocampus · 2002 Granule cells with recurrent basal dendrites (RBDs) were previously reported in both control and epileptic rats. RBDs are dendrites that arise from the basal half of granule cell bodies and curve toward and extend into the molecular layer. They are increas ... Full text Link to item Cite

Glutamate receptor involvement in dentate granule cell epileptiform activity evoked by mossy fiber stimulation.

Journal article Brain Res · October 5, 2001 In many persons with temporal lobe epilepsy, dentate granule cells form an interconnected synaptic network. This recurrent mossy fiber circuit mediates reverberating excitation that may facilitate seizure propagation by synchronizing granule cell discharge ... Full text Link to item Cite

Synaptically-released zinc inhibits N-methyl-D-aspartate receptor activation at recurrent mossy fiber synapses.

Journal article Brain Res · August 10, 2001 Hippocampal slices from pilocarpine-treated rats were used to explore the effect of zinc released at mossy fiber synapses on dentate granule cells. Chelation of zinc enhanced the N-methyl-D-aspartate (NMDA) receptor-mediated component of the excitatory pos ... Full text Link to item Cite

Lack of effect of mossy fiber-released zinc on granule cell GABA(A) receptors in the pilocarpine model of epilepsy.

Journal article J Neurophysiol · May 2001 The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in the epileptic brain and serves as a mechanism for synchronization of granule cell epileptiform activity. It has been suggested that this pathway also promotes epileptiform activ ... Full text Link to item Cite

Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer.

Journal article Brain Res · February 2, 2001 Several investigators have shown the existence of dentate granule cells in ectopic locations within the hilus and molecular layer using both Golgi and retrograde tracing studies but the ultrastructural features and synaptic connections of ectopic granule c ... Full text Link to item Cite

Status epilepticus-induced hilar basal dendrites on rodent granule cells contribute to recurrent excitatory circuitry.

Journal article J Comp Neurol · December 11, 2000 Mossy fiber sprouting into the inner molecular layer of the dentate gyrus is an important neuroplastic change found in animal models of temporal lobe epilepsy and in humans with this type of epilepsy. Recently, we reported in the perforant path stimulation ... Full text Link to item Cite

Modest increase in extracellular potassium unmasks effect of recurrent mossy fiber growth.

Journal article J Neurophysiol · November 2000 Featured Publication The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in many persons with temporal lobe epilepsy. The new connections among granule cells provide a novel mechanism of synchronization that could enhance the participation of these cell ... Full text Link to item Cite

gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester selectively blocks inhibitory synaptic transmission in rat dentate gyrus.

Journal article Eur J Pharmacol · March 17, 2000 gamma-Aminobutyrate, alpha-carboxy-2-nitrobenzyl ester (cGABA) is a stable photoactivatable probe used to study gamma-aminobutyrate (GABA) receptors. GABA is released from this compound when it is exposed to ultraviolet light, but little is known about the ... Full text Link to item Cite

Benzodiazepines protect hippocampal neurons from degeneration after transient cerebral ischemia: an ultrastructural study.

Journal article Neuroscience · 2000 The ability of full and partial benzodiazepine receptor agonists to prevent DNA fragmentation and neuronal death after transient cerebral ischemia was investigated in the Mongolian gerbil. Diazepam (10mg/kg, i.p.) or the partial agonist imidazenil (3mg/kg, ... Full text Link to item Cite

Mossy fiber-granule cell synapses in the normal and epileptic rat dentate gyrus studied with minimal laser photostimulation.

Journal article J Neurophysiol · October 1999 Featured Publication Dentate granule cells become synaptically interconnected in the hippocampus of persons with temporal lobe epilepsy, forming a recurrent mossy fiber pathway. This pathway may contribute to the development and propagation of seizures. The physiology of mossy ... Full text Link to item Cite

The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.

Journal article Nat Genet · April 1999 Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Dros ... Full text Link to item Cite

Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth.

Journal article J Neurophysiol · April 1999 Featured Publication A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells ... Full text Link to item Cite

Proline-induced inhibition of glutamate release in hippocampal area CA1.

Journal article Brain Res · September 26, 1997 Concentrations of proline typical of human CSF have been shown to potentiate transmission at Schaffer collateral-commissural synapses on CA1 pyramidal cells of the rat hippocampus. This study tested the hypothesis that proline enhances excitatory synaptic ... Full text Link to item Cite

Proline-induced potentiation of glutamate transmission.

Journal article Brain Res · July 4, 1997 The amino acid proline has long been suspected to serve as a modulator of synaptic transmission in the mammalian brain, but no such function has been identified. The selective expression of high affinity proline transport by a subset of glutamate pathways ... Full text Link to item Cite

Sodium-dependent proline and glutamate uptake by hippocampal synaptosomes during postnatal development.

Journal article Brain Res Dev Brain Res · June 18, 1997 NA(+)-dependent uptake of proline and glutamate by hippocampal synaptosomes was studied during postnatal development. At all ages from 9 days to adulthood, hippocampal synaptosomes transported proline by both a high-affinity and a low-affinity process, whe ... Full text Link to item Cite

Regulation of alternative splicing of NMDAR1 in the kindling model.

Journal article Brain Res Mol Brain Res · September 5, 1996 Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Sever ... Full text Link to item Cite

A novel nonopioid action of enkephalins: competitive inhibition of the mammalian brain high affinity L-proline transporter.

Journal article Mol Pharmacol · June 1996 The high affinity L-proline transporter (PROT) is a member of the family of Na+ (and Cl-)-dependent plasma membrane transport proteins that comprises transporters for several neurotransmitters, osmolytes, and metabolites. The brain-specific expression of P ... Link to item Cite

Polyamines antagonize N-methyl-D-aspartate-evoked depolarizations, but reduce Mg2+ block.

Journal article Eur J Pharmacol · May 4, 1995 This study utilized a grease-gap preparation to investigate the effects of polyamines on responses of CA1 hippocampal pyramidal cells to N-methyl-D-aspartate (NMDA) and on the block of the NMDA channel by Mg2+. In the absence of added Mg2+, 1,10-diaminodec ... Full text Link to item Cite

Release of glutamate and aspartate from CA1 synaptosomes: selective modulation of aspartate release by ionotropic glutamate receptor ligands.

Journal article J Neurochem · April 1995 Synaptosomes prepared from area CA1 of the rat hippocampus were used to determine (a) whether Schaffer collateral-commissural-ipsilateral associational terminals release both aspartate and glutamate in a Ca(2+)-dependent manner when reuptake of released gl ... Full text Link to item Cite

Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.

Journal article J Neurochem · March 1995 Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3-derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 mi ... Full text Link to item Cite

Hippocampal mossy fiber sprouting and synapse formation after status epilepticus in rats: visualization after retrograde transport of biocytin.

Journal article J Comp Neurol · February 20, 1995 In complex partial epilepsy and in animal models of epilepsy, hippocampal mossy fibers appear to develop recurrent collaterals that invade the dentate molecular layer. Mossy fiber collaterals have been proposed to subserve recurrent excitation by forming g ... Full text Link to item Cite

Kindling induces the long-lasting expression of a novel population of NMDA receptors in hippocampal region CA3.

Journal article J Neurosci · July 1994 Kindling refers to a phenomenon in which repeated application of initially subconvulsive electrical stimulations produces limbic and clonic motor seizures of progressively increasing severity. Once established, the increased excitability is lifelong. Enhan ... Full text Link to item Cite

Kindling reduces sensitivity of CA3 hippocampal pyramidal cells to competitive NMDA receptor antagonists.

Journal article Neuropharmacology · February 1994 Kindling is a form of experimental epilepsy in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. A previous study demonstrated that kindling enhances the sensitivity of hippocampal CA3 pyramidal cells to N ... Full text Link to item Cite

The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1.

Journal article Eur J Pharmacol · December 21, 1993 Riluzole is believed to exert its anticonvulsant and neuroprotective actions by reducing glutamate release. This study demonstrated that 10-30 microM riluzole reduces the K(+)-evoked release of glutamate and aspartate from slices of hippocampal area CA1. O ... Full text Link to item Cite

NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells.

Journal article Eur J Pharmacol · August 14, 1992 This study investigated the actions of proline on CA1 hippocampal pyramidal cells with use of slice preparations. Bath-applied L-proline first induced these cells to fire multiple orthodromic population spikes in response to a single stimulus and then bloc ... Full text Link to item Cite

Autoradiographic localization of proline uptake in excitatory hippocampal pathways.

Journal article Hippocampus · July 1992 An autoradiographic method was developed to localize sites of high-affinity, Na(+)-dependent proline uptake in the rat hippocampal formation. Hippocampal slices were incubated with [3H]proline, fixed with a glutaraldehyde/carbodiimide mixture, and cut into ... Full text Link to item Cite

Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA.

Journal article J Neurosci · May 1992 Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensit ... Full text Link to item Cite

Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil.

Journal article J Cereb Blood Flow Metab · July 1991 This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neoco ... Full text Link to item Cite

Autoreceptor regulation of glutamate and aspartate release from slices of the hippocampal CA1 area.

Journal article J Neurochem · May 1991 Slices of hippocampal area CA1 were employed to test the hypothesis that the release of glutamate and aspartate is regulated by the activation of excitatory amino acid autoreceptors. In the absence of added Mg2+, N-methyl-D-aspartate (NMDA)-receptor antago ... Full text Link to item Cite

Increased AMPA-sensitive quisqualate receptor binding and reduced NMDA receptor binding in epileptic human hippocampus.

Journal article J Neurosci · February 1991 Based on results from the kindling model of epilepsy, we hypothesized that enhanced binding of radioligands to the NMDA receptor and decreased binding to the alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA)-sensitive quisqualate (ASQ) receptor ... Full text Link to item Cite

Cholecystokinin blocks some effects of kainic acid in CA3 region of hippocampal slices.

Journal article Peptides · 1991 We investigated the relationship between the effects of cholecystokinin (CCK) and kainic acid (KA) in the CA3 region of hippocampal slices from rats. As has been reported previously, KA in nanomolar concentrations caused spontaneous epileptiform discharges ... Full text Link to item Cite

Postischemic synaptic excitation and N-methyl-D-aspartate receptor activation in gerbils.

Journal article Stroke · November 1990 Transient forebrain ischemia leads to the delayed degeneration of CA1b hippocampal pyramidal cells. In previous studies using the gerbil carotid occlusion model, we demonstrated that CA1b pyramidal cell degeneration is preceded by a period of enhanced exci ... Link to item Cite

Developmental increase in the sensitivity to magnesium of NMDA receptors on CA1 hippocampal pyramidal cells.

Journal article Brain Res Dev Brain Res · October 1, 1990 The N-methyl-D-aspartate (NMDA) receptor is involved in processes, such as associative learning, that are particularly important during early postnatal development. It has been suggested that the activity and regulation of this receptor changes during deve ... Full text Link to item Cite

A simple, inexpensive method of monitoring brain temperature in conscious rodents.

Journal article J Neurosci Methods · August 1990 A method was developed to monitor brain temperature in conscious, unrestrained rodents. A commercially available thermocouple microprobe was modified so that it could be screwed firmly into a guide cannula that had been stereotactically implanted in the br ... Full text Link to item Cite

Stimulation-induced status epilepticus: role of the hippocampal mossy fibers in the seizures and associated neuropathology.

Journal article Brain Res · March 26, 1990 A study of seizure activity and neuronal cell death produced by intracerebroventricular kainic acid had suggested that seizures conveyed by the hippocampal mossy fibers are more damaging to CA3 pyramidal cells than seizures conveyed by other pathways. To t ... Full text Link to item Cite

Effects of transient forebrain ischemia in area CA1 of the gerbil hippocampus: an in vitro study.

Journal article Adv Exp Med Biol · 1990 Selective delayed post-ischemic degeneration of CA1b neurons takes place in tissue slices in vitro as it does in brain in situ. Therefore neither selectivity nor the delay of the process can be explained by vascular factors. Changes of orthodromic evoked p ... Full text Link to item Cite

Selective neocortical and thalamic cell death in the gerbil after transient ischemia.

Journal article Neuroscience · 1990 In animal models of transients ischemia, selective vulnerability and delayed neuronal death in the hippocampus have been extensively described. However, little is known about selective damage in the neocortex and the thalamus, even though deficits in senso ... Full text Link to item Cite

Kainate and quisqualate receptor autoradiography in rat brain after angular bundle kindling.

Journal article Neuroscience · 1990 The kainate and quisqualate types of excitatory amino acid receptor were visualized autoradiographically in brain sections from rats kindled by stimulating the angular bundle. Kainate receptors were labeled with [3H]kainate and quisqualate receptors with L ... Full text Link to item Cite

Electron microscopic study of the gerbil dentate gyrus after transient forebrain ischemia.

Journal article Acta Neuropathol · 1990 Silver impregnation performed 1-2 days after transient forebrain ischemia in the Mongolian gerbil demonstrated terminal-like granular deposits in the outer two-thirds of the hippocampal dentate molecular layer (perforant path terminal zone), even though ne ... Full text Link to item Cite

Regulation of glutamate and aspartate release from the Schaffer collaterals and other projections of CA3 hippocampal pyramidal cells.

Journal article Prog Brain Res · 1990 Excitatory synaptic transmission in the CNS can be modulated by endogenous substances and metabolic states that alter release of the transmitter, usually glutamate and/or aspartate. To explore this issue, we have studied the release of endogenous glutamate ... Full text Link to item Cite

Kindling, prenatal exposure to ethanol and postnatal development selectively alter responses of hippocampal pyramidal cells to NMDA.

Journal article Adv Exp Med Biol · 1990 Our studies suggest that treatments, such as kindling and exposure to ethanol in utero, which produce irreversible pathological changes in brain function also selectively alter neuronal responses to NMDA. We have identified increases in agonist potency, wh ... Full text Link to item Cite

Postischemic synaptic excitation and N-methyl-D-aspartate receptor activation in gerbils

Journal article Stroke · 1990 Transient forebrain ischemia leads to the delayed degeneration of CA1b hippocampal pyramidal cells. In previous studies using the gerbil carotid occlusion model, we demonstrated that CA1b pyramidal cell degeneration is preceded by a period of enhanced exci ... Cite

Postischemic synaptic physiology in area CA1 of the gerbil hippocampus studied in vitro.

Journal article J Neurosci · November 1989 After transient forebrain ischemia in the Mongolian gerbil, CA1b hippocampal pyramidal cells degenerate during a period of 2-4 d. We tested the hypothesis that this delayed neuronal death is preceded by excessive synaptic excitation. Hippocampal slices wer ... Full text Link to item Cite

Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro.

Journal article Brain Res · October 23, 1989 The effects of glucose deficiency on (1) the K+-evoked release of glutamate and aspartate and (2) excitatory synaptic transmission were studied in the Schaffer collateral-commissural-ipsilateral associational (SCCIA) projection to area CA1 of the rat hippo ... Full text Link to item Cite

N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex.

Journal article Proc Natl Acad Sci U S A · October 1989 Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) rec ... Full text Link to item Cite

Biochemical evidence for enhanced sensitivity to N-methyl-D-aspartate in the hippocampal formation of kindled rats.

Journal article Brain Res · September 4, 1989 The inhibitory effect of N-methyl-D-aspartate (NMDA) upon carbachol-stimulated phosphoinositide (PI) hydrolysis was studied in transverse hippocampal slices prepared from control and amygdaloid kindled rats. Kindling significantly increased the inhibitory ... Full text Link to item Cite

A grease-gap method for studying the excitatory amino acid pharmacology of CA1 hippocampal pyramidal cells.

Journal article J Neurosci Methods · August 1989 A grease-gap method for studying the pharmacology of CA1 hippocampal pyramidal cells was developed with use of rat hippocampal slices that included only area CA1 and the retrohippocampal area. These slices were transferred to a two-compartment superfusion ... Full text Link to item Cite

Kainic acid inhibits cholecystokinin release from rat hippocampal slices.

Journal article Neurosci Lett · May 22, 1989 Antagonistic interactions between cholecystokinin (CCK) and nanomolar concentrations of kainic acid (KA) have been reported in area CA3 of the rat hippocampal slice. This study tested the possibility that kainic acid inhibits the release of CCK. Elevated K ... Full text Link to item Cite

N-methyl-D-aspartate receptor autoradiography in rat brain after angular bundle kindling.

Journal article Brain Res · March 20, 1989 The specific binding of L-[3H]glutamate to N-methyl-D-aspartate (NMDA) receptors in brain regions of kindled rats was visualized autoradiographically and quantitated. When assayed 28 days after the last evoked seizure, NMDA receptor binding had declined by ... Full text Link to item Cite

Absence of electrographic seizures after transient forebrain ischemia in the Mongolian gerbil.

Journal article Brain Res · January 2, 1989 EEG was continuously recorded from Mongolian gerbils for 4 days after transient bilateral forebrain ischemia, to determine whether ischemic brain damage in this species is necessarily associated with seizures. Gerbils were chronically implanted with EEG re ... Full text Link to item Cite

Lesions of excitatory pathways reduce hippocampal cell death after transient forebrain ischemia in the gerbil.

Journal article Acta Neuropathol · 1989 Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocamp ... Full text Link to item Cite

Novel approach to studying N‐methyl‐D‐aspartate receptor function in the kindling model of epilepsy

Journal article Drug Development Research · January 1, 1989 Kindling is the most widely studied animal model of epilepsy. This manuscript reviews studies of the role of N‐methyl‐D‐aspartate (NMDA) receptors in the kindling model. Pharmacologic studies suggest that 1) NMDA receptor activation contributes to the deve ... Full text Cite

Selective neuronal death after transient forebrain ischemia in the Mongolian gerbil: a silver impregnation study.

Journal article Neuroscience · November 1988 An important feature of ischemic brain damage is the exceptional vulnerability of specific neuronal populations and the relative resistance of others. Silver impregnation was used to delineate the extent and time-course of neuronal degeneration produced by ... Full text Link to item Cite

Regulation of glutamate and aspartate release from slices of the hippocampal CA1 area: effects of adenosine and baclofen.

Journal article J Neurochem · November 1988 Glutamate and/or aspartate is the probable transmitter released from synaptic terminals of the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers in area CA1 of the rat hippocampal formation. Slices of the CA1 area were empl ... Full text Link to item Cite

Ontogenetic changes in laminar distribution of ornithine decarboxylase during development of cerebellar cortex: autoradiographic localization with [3H]alpha-difluoromethylornithine.

Journal article Neuroscience · November 1988 Ornithine decarboxylase is the first enzyme in the biosynthesis of the polyamines, which control macromolecule synthesis during cellular development. Polyamines appear to play a critical role in the development of the rat cerebellar cortex, since postnatal ... Full text Link to item Cite

Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration.

Journal article Neuroscience · September 1988 The effects of a hippocampal mossy fiber lesion have been determined on neuronal degeneration and limbic seizures provoked by the subsequent intracerebroventricular administration of kainic acid to unanesthetized rats. Mossy fiber lesions were made either ... Full text Link to item Cite

Toxicity of L-proline toward rat hippocampal neurons.

Journal article Brain Res · July 19, 1988 Intrahippocampal injections of L-proline, a neutral amino acid excitant, non-selectively destroyed pyramidal and granule cells. Co-administration of equimolar kynurenate, an excitatory amino acid antagonist, markedly reduced the extent of neuronal cell dea ... Full text Link to item Cite

Mossy fiber lesion reduces the probability that kainic acid will provoke CA3 hippocampal pyramidal cell bursting.

Journal article Brain Res · February 9, 1988 Hippocampal slices prepared from rats which had received a mossy fiber lesion differed in their response to 50 nM kainic acid. Those slices in which the mossy fiber projection had been substantially destroyed were significantly less likely to develop epile ... Full text Link to item Cite

On the relation between seizures and brain lesions after intracerebroventricular kainic acid.

Journal article Neurosci Lett · January 11, 1988 To analyze the relation between kainic acid-induced limbic seizures and the associated brain lesions, various doses of kainic acid (117-940 pmol) were administered intracerebroventricularly to unanesthetized rats. Rats which experienced status epilepticus ... Full text Link to item Cite

Sodium-dependent proline uptake in the rat hippocampal formation: association with ipsilateral-commissural projections of CA3 pyramidal cells.

Journal article J Neurochem · October 1987 Na+-dependent uptake of L-[3H]proline was measured in a crude synaptosomal preparation from the entire rat hippocampal formation or from isolated hippocampal regions. Among hippocampal regions, Na+-dependent proline uptake was significantly greater in area ... Full text Link to item Cite

The effects of cholecystokinin and cholecystokinin antagonists on synaptic function in the CA1 region of the rat hippocampal slice.

Journal article Brain Res · July 7, 1987 The effects of two CCK antagonists, benzotript and proglumide, and of sulfated and non-sulfated cholecystokinin octapeptide (CCK-8-S and CCK-8-NS), were studied in the CA1 region of the rat hippocampal slice. Both benzotript and proglumide shifted presynap ... Full text Link to item Cite

A model of status epilepticus based on electrical stimulation of hippocampal afferent pathways.

Journal article Exp Neurol · June 1987 A new model of status epilepticus has been developed in the unanesthetized rat. The model involves repetitive tetanic stimulation of hippocampal afferent pathways. Pulse trains were delivered according to a fixed schedule (0.2 to 0.4-ms monophasic rectangu ... Full text Link to item Cite

Sodium-independent binding of L-[3H]proline to hippocampal synaptic membranes.

Journal article Eur J Pharmacol · November 4, 1986 L-[3H]Proline binds specifically and saturably to rat hippocampal synaptic membranes in the absence of inorganic ions. Saturation isotherms constructed in Hepes-Tris buffer best fit a model of a single independent population of binding sites with a dissoci ... Full text Link to item Cite

Efficacy of baclofen and phenobarbital against the kainic acid limbic seizure-brain damage syndrome.

Journal article J Pharmacol Exp Ther · November 1986 Baclofen and phenobarbital were tested for anticonvulsant efficacy against limbic seizures produced by i.c.v. infusion of kainic acid (KA) in unanesthetized rats. All rats treated with KA alone developed a prolonged status epilepticus associated with exten ... Link to item Cite

Comparison of seizures and brain lesions produced by intracerebroventricular kainic acid and bicuculline methiodide.

Journal article Exp Neurol · September 1986 Intracerebroventricular kainic acid produces in rats brain lesions similar to Ammon's horn sclerosis in humans. To test the hypothesis that these lesions result indirectly from prolonged seizure activity and not from a direct action of kainic acid on the n ... Full text Link to item Cite

Baclofen suppresses bursting activity induced in hippocampal slices by differing convulsant treatments.

Journal article Eur J Pharmacol · July 31, 1986 Epileptiform activity was induced in area CA3 of hippocampal slices by superfusion of medium containing 50 microM bicuculline and 3.5 mM K, 50 microM bicuculline and 5 mM K, 50 nM kainic acid and 3.5 mM K, or 7 mM K. Burst potentials were recorded at rates ... Full text Link to item Cite

Autoradiographic localization of ornithine decarboxylase in cerebellar cortex of the developing rat with [3H]alpha-difluoromethylornithine.

Journal article Neuroscience · 1986 Ornithine decarboxylase was autoradiographically localized in the developing rat cerebellar cortex after intracisternal injection of [3H]alpha-difluoromethylornithine, a specific, irreversible inhibitor of the enzyme. At nine days of age, when cerebellar o ... Full text Link to item Cite

Effects of neonatal treatment with 6-aminonicotinamide on basal and isoproterenol-stimulated ornithine decarboxylase activity in cerebellum of the development rat.

Journal article Biochem Pharmacol · September 15, 1985 6-Aminonicotinamide (6-AN) is a nicotinic acid (vitamin B3) antagonist which, when administered to immature animals, has a profound influence on brain development. To explore the biochemical mechanisms which underlie these actions, we evaluated effects of ... Full text Link to item Cite

Binding sites for L-[3H]glutamate on hippocampal synaptic membranes: three populations differentially affected by chloride and calcium ions.

Journal article J Neurochem · June 1985 The effects of Cl- and Ca2+ were studied on the specific binding of L-[3H]glutamate to multiple sites on rat hippocampal synaptic membranes. Quisqualate (5 microM) or DL-2-amino-4-phosphonobutyrate (2-APB) (300 microM) was used to discriminate two previous ... Full text Link to item Cite

Impaired development of cerebellar cortex in rats treated postnatally with alpha-difluoromethylornithine.

Journal article Neuroscience · May 1985 alpha-Difluoromethylornithine specifically and irreversibly inhibits the enzyme ornithine decarboxylase. Ornithine decarboxylase catalyses the initial step in the synthesis of polyamines, which are thought to play an essential role in growth and developmen ... Full text Link to item Cite

Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats.

Journal article J Neurosci · April 1985 In the rat hippocampal formation, degeneration of CA4-derived afferent fibers provokes the growth of mossy fiber collaterals into the fascia dentata. These aberrant fibers subsequently form granule cell-granule cell synapses. The hippocampal slice preparat ... Full text Link to item Cite

Reduced kainic acid binding in rat hippocampal formation after limbic kindling.

Journal article Brain Res · December 3, 1984 The specific binding of [3H]kainic acid to hippocampal membranes was examined autoradiographically in rats kindled by tetanic stimulation of the amygdala or angular bundle. One day after the last of 3 class 4-5 kindled seizures, the specific binding of [3H ... Full text Link to item Cite

Selective and reversible increase in the number of quisqualate-sensitive glutamate binding sites on hippocampal synaptic membranes after angular bundle kindling.

Journal article Brain Res · July 30, 1984 The specific binding of L-[3H]glutamate to hippocampal synaptic membranes was examined in rats kindled by tetanic stimulation of the angular bundle. One day after the last of a minimum of 3 class 4 kindled seizures, the binding of L-[3H]glutamate to a quis ... Full text Link to item Cite

Evidence for differential localization of two binding sites for L-[3H]glutamate in rat fascia dentata.

Journal article Brain Res · October 16, 1983 Two binding sites for L-[3H]glutamate were tentatively localized in rat fascia dentata by determining the effects of selective lesions on specific binding. Both destruction of dentate granule cells with colchicine and ablation of the ipsilateral entorhinal ... Full text Link to item Cite

Effects of baclofen on synaptically-induced cell firing in the rat hippocampal slice.

Journal article Br J Pharmacol · September 1983 The effects of baclofen on the synaptically-induced firing of pyramidal and granule cell populations were tested in the rat hippocampal slice. Population spikes were evoked by stimulating excitatory pathways in the presence and absence of bath-applied drug ... Full text Link to item Cite

L-[3H]Glutamate binding to hippocampal synaptic membranes: two binding sites discriminated by their differing affinities for quisqualate.

Journal article J Neurochem · August 1983 The excitatory glutamate analogs quisqualate and ibotenate were employed to distinguish multiple binding sites for L-[3H]glutamate on freshly prepared hippocampal synaptic membranes. The fraction of bound radioligand that was displaceable by 5 microM quisq ... Full text Link to item Cite

Anticonvulsant-like actions of baclofen in the rat hippocampal slice.

Journal article Br J Pharmacol · April 1983 1 The effects of baclofen were tested on epileptiform discharge in the rat hippocampal slice. Slices were superfused with bicuculline methiodide (100 microM) and maximal periods of afterdischarge were evoked by stimulating the Schaffer collateral-commissur ... Full text Link to item Cite

L-[3H]glutamate binding to hippocampal synaptic membranes: Two binding sites discriminated by their differing affinities for quisqualate

Journal article Journal of Neurochemistry · 1983 The excitatory glutamate analogs quisqualate and ibotenate were employed to distinguish multiple binding sites for L-[3H]glutamate on freshly prepared hippocampal synaptic membranes. The fraction of bound radioligand that was displaceable by 5 μM quisquala ... Cite

Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice.

Journal article J Pharmacol Exp Ther · November 1982 The effects of baclofen, an antispastic drug, on excitatory transmission were tested by bath application to the hippocampal slice preparation. (+/-)-Baclofen (20 microM) strongly depressed extracellularly recorded synaptic responses to stimulation of proje ... Link to item Cite

Autoradiographic evidence that septohippocampal fibers reinnervate fascia dentata denervated by entorhinal lesion during development.

Journal article Anat Embryol (Berl) · September 1982 The projection from the ventromedial septum to the fascia dentata was investigated autoradiographically in normal adult rats and in adult rats whose entorhinal cortex had been removed unilaterally at the age of 11 days. In the fascia dentata of normal rats ... Full text Link to item Cite

Complex binding of L-[3H]glutamate to hippocampal synaptic membranes in the absence of sodium.

Journal article J Neurochem · April 1982 Specific binding of L-[3H]glutamate was investigated with a thoroughly washed synaptic membrane preparation from rat hippocampal formation, a region of brain densely innervated by putatively glutamatergic fibers. L-[3H]Glutamate bound rapidly, saturably, a ... Full text Link to item Cite

Desensitization-like changes in GABA receptor binding of rat fascia dentata after entorhinal lesion.

Journal article Neurosci Lett · November 4, 1981 Destruction of the hippocampal perforant path fibers reduced the binding of [3H]GABA to membranes prepared from the rat fascia dentata. This result could be detected 1--4 months after surgery, but not in 10 days or less. Such a delayed response appears mos ... Full text Link to item Cite

Perforant path lesion depletes glutamate content of fascia dentata synaptosomes.

Journal article Neurosci Lett · September 25, 1981 Destruction of the hippocampal perforant path fibers reduces the glutamate content of a crude synaptosomal fraction of the rat fascia dentata by about 40%, but does not reduce the aspartate content. This result supports the hypothesis that the perforant pa ... Full text Link to item Cite

Fate of the hippocampal mossy fiber projection after destruction of its postsynaptic targets with intraventricular kainic acid.

Journal article J Comp Neurol · March 10, 1981 Intraventricular injections of kainic acid were used to create a model of selective cell death in order to study the fate of afferent projections that are deprived of their postsynaptic targets. This treatment rapidly destroyed hippocampal CA3 pyramidal ce ... Full text Link to item Cite

Evidence from lesion studies for epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation.

Journal article Brain Res · February 2, 1981 The toxicity of kainic acid toward rat hippocampal neurons depends on the presence of specific excitatory afferents. Acute destruction of the critical pathway essentially abolishes the neurotoxicity of intraventricular kainic acid, but some or all hippocam ... Full text Link to item Cite

Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid.

Journal article J Comp Neurol · July 15, 1980 Degeneration of hippocampal CA3 pyramidal cells was investigated by light and electron microscopy after intraventricular injection of the potent convulsant, kainic acid. Electron microscopy revealed evidence of pyramidal cell degeneration within one hour. ... Full text Link to item Cite

Loss and reacquisition of hippocampal synapses after selective destruction of CA3-CA4 afferents with kainic acid.

Journal article Brain Res · June 9, 1980 Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells bilaterally in rats, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum of area CA1. Electron microscopic studies ... Full text Link to item Cite

Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid.

Journal article Brain Res · January 20, 1980 Intraventricular injections of kainic acid were used to destroy the hippocampal CA3-CA4 cells, thus denervating the inner third of the molecular layer of the fascia dentata and stratum radiatum and stratum oriens of area CA1. The responses of intact affere ... Full text Link to item Cite

Analysis of short-term plasticity at the perforant path-granule cell synapse.

Journal article Brain Res · December 7, 1979 Short-term plasticity was investigated at the perforant path-granule cell synapse in the hippocampal slice preparation. A successive decrement in the amplitude of the extracellular EPSP was obtained at all stimulus frequencies above 0.05 Hz. This effect of ... Full text Link to item Cite

Lesion-induced plasticity of high affinity choline uptake in the developing rat fascia dentata.

Journal article Brain Res · March 23, 1979 After removal of the perforant path input to the rat fascia dentata at the age of 11 days, cholinergic septohippocampal fibers invade the denervated area. We have examined the effect of this lesion on hemicholinium-sensitive, high affinity choline uptake a ... Full text Link to item Cite

The effect of acidic amino acid antagonists on synaptic transmission in the hippocampal formation in vitro.

Journal article Brain Res · March 23, 1979 The effects on synaptic efficacy of the putative acidic amino acid antagonists, 2-amino-4-phosphonobutyric acid (APB), 2-amino-3-phosphonopropionic acid (APP), 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethyl ester (GDEE), were tested by ... Full text Link to item Cite

Development of high affinity choline uptake and associated acetylcholine synthesis in the rat fascia dentata.

Journal article Brain Res · March 16, 1979 The ontogenic development of hemicholinium-sensitive, high affinity choline uptake and the synthesis of acetylcholine from exogenous choline have been studied in particulate preparations of the rat fascia dentata. Between 6 days of age and adulthood the ra ... Full text Link to item Cite

Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. II. Effects of partial entorhinal and simultaneous multiple lesions.

Journal article J Comp Neurol · February 15, 1977 It has been concluded previously that the septohippocampal fibers which project to the rat dentate gyrus extend or branch in the denervated area of the molecular layer following a complete ipsilateral entorhinal lesion. The septohippocampal fibers thus app ... Full text Link to item Cite

Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. I. Time course after complete unilateral entorhinal lesion at various ages.

Journal article J Comp Neurol · February 15, 1977 The entorhinal cortex of rats was removed at various times during development, and the reaction of the cholinergic septohippocampal input to the dentate gyrus was examined by use of acetylcholinesterase histochemistry. When the ipsilateral entorhinal corte ... Full text Link to item Cite