Timothy J. Teyler

The topological anatomy of the hippocampus: A clue to its function

The anatomy of the hippocampus and dentate gyrus is considered with respect to the topology of its afferents and efferents. The topological attributes of the hippocampal formation represent a four-dimensional array with the demensions being: the afferent input to laminated dendritic zones, the intrinsic tri-synaptic hippocampal system, the longitudinal and commissural association systems, and time. Within this four-dinmensional array, active foci can vary dynamically in space and time, depending upon the pattern of afferent activity. The features of hippocampal topology may relate to the role of the hippocampal formation in information storage and processing.

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.

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.

Synaptic plasticity in the hippocampal slice: functional consequences

There are 3 known forms of synaptic plasticity at CNS synapses: long-term potentiation (LTP) mediated by NMDA receptor activation, LTP mediated by voltage-dependent calcium channel (VDCC) activation, and long-term depression (LTD) mediated by the NMDA receptor. All 3 forms of synaptic plasticity can be observed in hippocampal CAl cells, all are induced by afferent activation, all involve Ca2+ influx, and all activate Ca(2+)-dependent mechanisms. We consider the functional consequences of the presence of 3, sometime opposing, forms of synaptic plasticity at the same synapse. We suggest that the 2 forms of LTP have different consequences for the synapse. We postulate that the co-existence of potentiating and depressing capabilities influences the network processing capabilities of neural networks.

Synaptic plasticity and secondary epileptogenesis

Publisher Summary One of Frank Morrells legacies is the proposition that there is a linkage between mechanisms underlying normal synaptic plasticity and the pathological mechanisms that give rise to seizure disorders. Such a process is thought to take place in kindling, which was initially described as the operation of synaptic plasticity following repeated activation. In fact, the stimulation parameters leading to kindling are identical to those used to induce long-term potentiation. Today, however, kindling is considered not primarily as an example of synaptic plasticity but rather as a model of secondary epileptogenesis—that is, the spread of epilepsy from a primary epileptic zone to distant but synaptically related brain regions. Still, similar mechanisms appear to be operative in the establishment of kindling foci and synaptic plasticity, a result Morrell anticipated. This chapter reviews some recent research in long-term potentiation (LTP) that has revealed additional potential links between synaptic plasticity and the development of secondary epileptogenic foci.

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.

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.

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.

α-Difluoromethylornithine decreases inhibitory transmission in hippocampal slices independently of its inhibitory effect on ornithine decar☐ylase

We tested the effect of DL -α-(difluoromethyl)ornithine (DFMO), a specific inhibitor of ornithin decar☐ylas (ODC), on recordings in area CA1 of rat hippocampal slices. In the concentration range in which it is used as an ODC inhibitor, DFMO increased neuronal excitability and blocked paired-pulse inhibition. The effect of DFMO was reversed by perfusing the slice with normal bathing solution. These effects were not attenuated by the simultaneous addition of putrescine; thus the activity ofDFMO was not related to a decrease in putrescine caused by the inhibition of ODC. Mediation by the N -methyl- D -aspartate (NMDA)receptor was ruled out because DL -2-amino-5-phosphonovalerate (APV) , an NMDA antagonist, did not block the effect of DFMO. Intracellular and extracellular recordings of pharmacologically isolated IPSPs supported the notion that DFMO depressed GABAergic transmission. DFMO has frequently been used as a tool to study the role of the ODC-polyamine system in neural preparations. This report suggests that the results from such studies must be interpreted with caution. In addition, our findings raise questions about the proposed use of DFMO as a neuroprotective agent against excitotoxicity.