Biomedical subjects

T J Teyler

Publications and source records attributed to T J Teyler.

At least 19 recordsLinked to original sources

PubMed1992

Induction of NMDA receptor-independent long-term potentiation (LTP) in visual cortex of adult rats.

The aim of this study was to examine: (1) whether long-term potentiation (LTP) can be induced in slices from adult rat visual cortex under conditions where inhibition is not antagonized, and (2) the role of N-methyl-D-aspartate (NMDA) receptors in its induction. The field potential elicited in layer III in response to stimulation of the subcortical white matter consisted of a component with peak latency 5-8 ms (N1) and, in most slices, a second component with peak latency 13-19 ms (N2). N1 was generated via both kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and NMDA receptor activation as revealed by bath application of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). N2 was insensitive to APV in most of the slices and was probably polysynaptic since it did not follow stimulation at 0.5 Hz. Tetanic stimulation of the white matter in normal medium induced LTP of N1; in some slices N2 also potentiated. Tetanic stimulation in the presence of APV also induced LTP of N1 and sometimes N2. LTP of N1 induced in APV was of a larger magnitude, and was expressed more quickly than LTP induced in normal medium. It appears that the known reduction of NMDA receptor activity in adult neocortex is accompanied by the development of other mechanisms that maintain synaptic plasticity; these mechanisms seem to operate more efficiently in absence of NMDA receptor activation.

Animals↗

PubMed1992

N-methyl-D-aspartate receptor-independent long-term potentiation in area CA1 of rat hippocampus: input-specific induction and preclusion in a non-tetanized pathway.

We previously reported that an N-methyl-D-aspartate receptor-independent component of long-term potentiation with an apparent delayed onset can be induced in area CA1 of the hippocampus. Here we show that some but not all of this delay in onset can be accounted for by a transient heterosynaptic depression. We also show that N-methyl-D-aspartate receptor-independent long-term potentiation is induced only in the input pathway tetanized, and not in a second pathway. However, prior induction of N-methyl-D-aspartate receptor-independent long-term potentiation in one pathway precludes later induction in an independent pathway. Calcium entry through dihydropyridine-sensitive Ca2+ channels may be a critical step for induction of N-methyl-D-aspartate receptor-independent long-term potentiation in area CA1 [Grover L. M. and Teyler T.J. (1990) Nature 347, 477-479]. Since the distribution [Westenbroek R. E. et al. (1990) Nature 347, 281-284] of dihydropyridine-sensitive Ca2+ channels in CA1 neuron dendrites does not suggest a basis for input-specific induction of long-term potentiation, an additional process may confer the specificity we observed. Tetanic stimulation of afferents into area CA1 can elicit several processes: a transient heterosynaptic depression, and a transient homosynaptic potentiation, as well as N-methyl-D-aspartate receptor-dependent and -independent long-term potentiation.

2-Amino-5-phosphonovalerate↗

PubMed1992

Use of computer-assisted courseware in teaching neuroscience: the Graphic Brain.

We describe the development of a computer-assisted instructional tool for the neurosciences. Designed to run on readily available MS-DOS computers, the Graphic Brain utilizes computer-generated static and animated images and accompanying text to assist in instruction of neuroanatomy and neurophysiology. We have used the Graphic Brain in our medical neuroscience course and report that, as measured anecdotally and by test scores, it facilitates student comprehension of the space- and time-varying aspects of anatomy and physiology. When the Graphic Brain is used as an adjunct to lecture, we find that we can cover the same material in 75% of the time required using traditional methods.

Brain↗

PubMed1991

The role of NMDA receptors in long-term potentiation (LTP) and depression (LTD) in rat visual cortex.

The purpose of the present study was to improve our understanding of the role of NMDA receptors in neocortical synaptic plasticity. In slices of rat visual cortex the field potential elicited in layer III in response to white matter stimulation consisted of two components with peak latencies at 5-8 ms (EPSP1) and 12-19 ms (EPSP2). EPSP2 appeared to be polysynaptic since it did not follow stimulation at 0.5 Hz. EPSP1 consisted of both kainate/AMPA and NMDA receptor activity, as revealed by bath application of DNQX and APV. EPSP2 displayed a variable sensitivity to bath-applied APV. Tetanic stimulation of the white matter in normal medium consistently induced long-term potentiation of EPSP1. In the presence of APV, LTP of EPSP1 was induced only when EPSP2 was still present, while there was no change, or LTD was induced, when EPSP2 was completely blocked by APV. In rat visual cortex, blockade of NMDA receptor participation in the postsynaptic response to tetanic stimulation reduces the probability for LTP induction but does not necessarily prevent LTP; synaptic strength may still change in either direction depending, in part, on factors affecting the magnitude of postsynaptic depolarization during tetanus.

2-Amino-5-phosphonovalerate↗

PubMed1991

Cholinergic disinhibition in area CA1 of the rat hippocampus is not mediated by receptors located on inhibitory neurons.

We studied the effects of carbamylcholine (carbachol; CCh) on monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked 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). CCh (30 microM) blocked late afterhyperpolarizations but did not depress GABAA receptor-mediated fast monosynaptic IPSPs or GABAB receptor-mediated late monosynaptic IPSPs. In the presence of CCh the GABAB receptor agonist (+/- )-baclofen (2 microM) reversibly hyperpolarized pyramidal neurons and depressed monosynaptic IPSPs as under control conditions. Phorbol-12,13-diacetate (PDAc; 10 microM) increased fast and depressed late monosynaptic IPSPs, and prevented depression of IPSPs by baclofen. These results suggest that cholinergic disinhibition in area CA1 of the hippocampus results from decreased synaptic excitation of inhibitory neurons.

2-Amino-5-phosphonovalerate↗

PubMed1991

Baclofen-induced disinhibition in area CA1 of rat hippocampus is resistant to extracellular Ba2+.

The mechanism of disinhibition produced by (+/-)-baclofen was studied using intracellular recording in area CA1 of rat hippocampal slices. Baclofen reversibly depressed monosynaptic IPSPs evoked by direct activation of interneurons 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). Ba2+ prevented baclofen-induced hyperpolarization of pyramidal neurons but not depression of monosynaptic IPSPs by baclofen. Baclofen reversibly depressed monosynaptic IPSPs when applied close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that baclofen disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating receptors on the terminals of inhibitory neurons that are coupled to a Ba(2+)-insensitive effector mechanism.

2-Amino-5-phosphonovalerate↗

PubMed1991

Evidence for mu opiate receptors on inhibitory terminals in area CA1 of rat hippocampus.

The mechanism of disinhibition produced by opioid peptides was studied using intracellular recording in area CA1 of rat hippocampal slices. The mu-selective opioid peptide [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO) reversibly depressed directly-activated, monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked 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) in a naloxone-sensitive manner. Depression of monosynaptic inhibitory postsynaptic potentials (IPSPs) by DAGO was not prevented by 1-2 mM Ba2+. DAGO reversibly depressed monosynaptic IPSPs when applied locally close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that DAGO disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating mu opiate receptors located on the terminals of inhibitory neurons, and by a Ba(2+)-insensitive mechanism.

2-Amino-5-phosphonovalerate↗

PubMed1991

Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus.

The effects of adenosine on inhibitory synaptic transmission in area CA1 were examined using the rat hippocampal slice preparation and intracellular recording. Adenosine did not change fast inhibitory synaptic potentials (IPSPs) but depressed late IPSPs evoked by direct activation of interneurons in the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Directly activated IPSPs were unchanged by the selective adenosine A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but CPT reversed hyperpolarization and depression of late IPSPs produced by adenosine. These results indicate that adenosine depresses disynaptic IPSPs in area CA1 by decreasing synaptic activation of inhibitory neurons.

2-Amino-5-phosphonovalerate↗

PubMed1991

An integrated multielectrode electrophysiology system.

An integrated system for recording and analyzing electrophysiological data from multiple channels is described. The system uses an MS-DOS microcomputer, a 16-channel amplifier, and multiple-tipped electrode arrays designed for use in intact and slice preparations. The system is designed for applications where the collection and analysis of multiple-channel electrophysiological data is desirable, including the construction of current source density (CSD) profiles from field potential data. The software incorporates on-line averaging, CSD and freeze-frame capabilities to guide the experiment in progress. Additional off-line analyses include multiple unit activity, power spectra, and automatic scans of data files for peak amplitude, area, latency, and slope within user-defined latency windows. All data and analyses can be exported to commercial statistical/graphical programs for the creation of publication-ready figures.

Amplifiers, Electronic↗

PubMed1991

Methods for studying the conductance changes associated with synaptic activation of forebrain slices: the interpretation of field potentials using CSD profiles.

In this report the cortical slice preparation and an array electrode that instantaneously records laminar field potentials are used to evaluate issues related to the interpretation of cortical CSD profiles. The major issues are: (1) what cell types are responsible for producing the source/sink pairs seen in CSD profiles; (2) what neurotransmitters are responsible for producing the sinks/sources seen in the CSD profile and do the sinks/sources reflect activation of receptors that produce inward currents, outward currents, or both; (3) can active and passive currents be distinguished; (4) do action potentials contribute to the CSD profile; and (5) can synaptic population with different kinetics and onset latencies be distinguished? Methods for analyzing neuronal circuits and analyzing CSDs quantitatively are discussed.

Animals↗

PubMed1991

Ontogenesis of the depressant activity of carbachol on synaptic activity in rat visual cortex.

We studied the ontogeny of muscarinic depression in the developing rat visual cortex using carbachol (a nonhydrolyzable cholinergic agonist) application to neocortical slices obtained from four postnatal age groups: 9-10 days, 15 days, 30-40 days and 18 months. Carbachol suppressed the evoked synaptic response of layers II-III to stimulation of layer II-III afferents. Atropine eliminated the carbachol effect, suggesting that it is mediated by muscarinic receptors. The results indicate a significant increase in muscarinic efficacy in the developing rat visual cortex.

Animals↗

PubMed1991

Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.

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 P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35,348; 0.1-1.0 mM). CGP 35,348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration [( Cl-]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35,348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABAA current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50-100 microM), DNQX and APV long-lasting depolarizing GABAA receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1990

The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus.

The actions of 2-hydroxy-saclofen (2-OH-S), a recently developed analog of baclofen, were studied at presynaptic GABAB receptors in the rat hippocampal slice. Baclofen (0.5-20 microM) reduces the amplitude of excitatory postsynaptic potentials (EPSPs) recorded from hippocampal CA1 pyramidal neurons. In the presence of 200-500 microM 2-OH-S, the synaptic depressant action of baclofen is significantly reduced. These data show that 2-OH-S is an effective antagonist at presynaptic GABAB receptors on excitatory terminals in the hippocampus.

Animals↗

PubMed1990

Two components of long-term potentiation induced by different patterns of afferent activation.

Long-term potentiation (LTP) of excitatory synaptic transmission could be a mechanism underlying memory. Induction of LTP requires Ca2+ influx into postsynaptic neurons through ion channels gated by NMDA (N-methyl-D-aspartate) receptors in hippocampus (area CA1 and dentate gyrus) and neocortex. Here we report that a component of LTP not requiring the activation of NMDA receptors can be induced in area CA1. The component is dependent on tetanus frequency, requires increases in postsynaptic intracellular Ca2+ concentrations, and is suppressed by an antagonist of voltage-dependent Ca2+ channels.

2-Amino-5-phosphonovalerate↗

PubMed1990

Differential effects of NMDA receptor antagonist APV on tetanic stimulation induced and calcium induced potentiation.

Enduring synaptic potentiation can be induced in area CA1 of hippocampus by tetanic stimulation and by exposure to a medium containing high Ca2+ concentration. Both tetanic stimulation and high Ca2+ induce potentiation through voltage-dependent, post-synaptic mechanisms. Tetanus-induced long-term potentiation (LTP) was blocked by 50 microM D,L-2-amino-5-phosphonovalerate (APV) as previously reported by others. In contrast, Ca2(+)-induced long-lasting potentiation was not reduced by 50 microM APV. Thus the mechanisms by which tetanic stimulation and exposure to high Ca2+ induce synaptic potentiation may differ.

2-Amino-5-phosphonovalerate↗

PubMed1990

Effects of extracellular potassium concentration and postsynaptic membrane potential on calcium-induced potentiation in area CA1 of rat hippocampus.

Long-lasting potentiation can be induced in area CA1 of hippocampus by a relatively brief (7-10 min) exposure to a higher (4.0 mM) than normal (2.0 mM) extracellular calcium concentration. We have found that long-lasting calcium-induced potentiation is dependent on extracellular potassium concentration. Slices exposed to high extracellular calcium in the presence of normal extracellular potassium (3.35 mM) showed a transient facilitation. Long-lasting potentiation was induced by exposure to high calcium only in slices also exposed to higher than normal extracellular potassium (6.25 mM). In intracellular experiments we found that injection of depolarizing current into postsynaptic neurons could substitute for high extracellular potassium. These results suggest that calcium-induced potentiation involves a postsynaptic, voltage-dependent mechanism. A similar conclusion has been reached for tetanus-induced potentiation. We also found that calcium-induced potentiation, like tetanus-induced potentiation, is not accompanied by an increase in postsynaptic input resistance.

Action Potentials↗

PubMed1990

A slice preparation preserving the callosal projection to contralateral visual cortex.

Due to the curved path they follow, the visual callosal projections to areas OC1 and OC2 of the rat visual cortex have been inaccessible to studies using brain slices. In this paper we describe a new slice preparation in which a curved cutting blade was used to obtain slices in which callosal fibers projecting to OC1 or OC2 are preserved. Stimulation of the contralateral white matter resulted in EPSPs recorded in layer II/III and V cells of OC2 studied with intracellular recording. Current source density analysis of extracellular field potentials collected in OC1 and OC2 revealed laminar current sink patterns paralleling the laminar distribution of callosal terminations reported by Miller and Vogt (Dev. Brain Res., 14 (1984) 304-309). Exposure of slices to 2 mM kynurenic acid reversibly abolished current sinks in OC1 recorded in response to callosal stimulation indicating that glutamate receptors mediate the response of OC1 to callosal afferent activity. This new slicing technique can be readily adapted to study other systems in the nervous system in which neural processes follow curved trajectories.

Animals↗

PubMed1990

Organization of cortical afferent and efferent pathways in the white matter of the rat visual system.

Fibers forming reciprocal connections between the dorsal lateral geniculate nucleus and primary visual cortex run in separate tracts in the white matter. The corticofugal fibers are organized into bundles which project through the coronal plane at an oblique angle. We have examined the organization of corticofugal fiber tracts within the white matter of the rat using cortical slices which encompassed the predicted trajectory of these fiber bundles. Field potentials were evoked in layer VI of visual cortex by focal stimulation of subcortical white matter using microbipolar electrodes. Two major responses were elicited: a short-latency and a longer-latency response. The short-latency response was elicited in the superficial strata of white matter with proximal stimulation sites and was obtained in deeper strata for more distant, lateral sites. The longer-latency response was associated with superficial strata in white matter at both proximal and distant stimulation sites. Based on the electrophysiological properties and the white matter location for eliciting these responses, it is likely that the short-latency response is due to antidromic activation of corticogeniculate fibers, whereas the longer-latency response probably arises from orthodromic activation of geniculocortical fibers. These findings provide an electrophysiological demonstration that cortical afferent and efferent pathways are segregated within the white matter and that they can be selectively activated by focal stimulation. The fact that the fiber bundle model successfully predicted the trajectory of corticofugal fibers provides additional support for this model of white matter organization. A double labeling technique which combined orthograde axonal transport and neuronal degeneration was used to examine the topographic arrangement of corticofugal fibers in the white matter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗