EXPERIMENTAL
NEUROLOGY
83, 664-667
(1984)
RESEARCH Common
NOTE
Synaptic Connections to Epileptic and Normal Neurons ALLEN R. WYLER~
Department
of Neurological
Surgery, Received
University September
of Washington,
Seattle,
Washington
98195
12, 1983
A normal and an epileptic firing neuron were recorded simultaneously from within a chronic epileptic focus. The cross-correlation histogram demonstrated that they received some common synaptic input even though their patterns of fning were markedly different.
During the last several years, this laboratory has been involved in the study of firing patterns of neurons within interictal precentral epileptogenic foci of monkeys. More recently, attention has been directed toward whether abnormal synchrony is a characteristic of such foci. To study this question we have begun to record two neurons simultaneously through the same microelectrode and to analyze data with cross-correlation histograms. This type of analysis has begun to yield some interesting observations, one of which is that two simultaneously recorded neurons may have what appears to be some commonality of synaptic input, yet fire with entirely different patterns; more specifically, one neuron may have a completely normal firing pattern whereas the other may fire patterns that are ascribed to epileptic neurons. Data were obtained from young adult, male Mzcacu muluttu monkeys which had been made chronically epileptic and subsequently prepared for chronic extracellular neuronal recording using previously reported techniques Abbreviations: AP-action potential, ISI-interspike interval. ’ This research was supported by National Institutes of Health research grant NS 04053 awarded by the National Institute of Neurological and Communicative Disorders and Stroke. The author is an affiliate of the Child Development and Mental Retardation Center, University of Washington. 664 0014-4886/84
$3.00
Copyright 0 1984 by Academic Pres. Inc. AI1 rights of reproduction in *ny form reserved.
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NEURONS
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(3, 4). Neurons were recorded from cortical area 4 during the monkey’s participation in an operant conditioning task which required it to operantly control the firing pattern of a single neuron (2). At the beginning of each experiment the electrode was positioned to record well isolated action potentials (AI%) from two individual neurons. The data were not accepted if excellent isolation of both units was not maintained throughout the entire recording period. Neurons were class&d as normal or epileptic by previous criteria (3). Fiire 1 ilhrstmtes interspike interval (ISI) h&grams and cross-correlation histograms from one representative experiment in which a normal (unit 1) and an epileptic (unit 2) unit were recorded simultaneously. Each IS1 histogram was composed of all ISIS between 1 to 150 ms during sequential 5-min behavioral periods. Each crosscorrelation histogram was generated from each 5-min period in the following manner: upon each occurrence of an AP from unit 1 (the larger AP of the two units), the computer searched for an AP from unit 2 that was within 13 ms before and then 13 ms alter unit 1. Thus, the histogram showed all ISIS of unit 2 that occurred within f 13 ms of unit 1. For this histogram, brings of unit 2 that were not within 13 ms of unit 1 were disregarded. (The Y-axis for the two types of histograms are not the same scale). Histograms in rows A-D correspond to the following 5-min periods: preconditioning, operant period, time-out period, and operant period. Reinforcement to the monkey was contingent upon the firing of unit 1. During all behavioral periods the IS1 histograms of unit 1 and unit 2 remained characteristic of a normal and epileptic precentral neuron, respectively. During the two operant periods the histograms of unit 1 shifted toward the reinforced IS1 range which suggested the monkey was participating in the operant task. However, the IS1 histograms for unit 2 changed much less between operant and nonoperant periods which is also a characteristic of epileptic neurons (3). However, in comparing the cross-correlation histograms for the same periods, it is seen that in comparison with the preconditioning period the unit 2 increased its tendency to fire an AP within 1 ms of unit 1 during all periods subsequent to the preconditioning period. The mechanism by which monkeys operantly control the firing rate and pattern of single cortical neurons is mediated by alferent feedback to the recorded neuron from peripheral receptors (2). Allum et al. (1) recently studied the synchrony and recruitment of simultaneously recorded neurons in precentral cortex during monkeys’ participation in a graded force precision finger grip operant task and found that many unit pairs also tended to fire within 1 ms of each other. They concluded that such a relationship was most likely due to a commonality of atferent projections from thalamus to the neurons. Thus, the relationship between the two units shown in Fig. 1 is also quite common for normal neurons recorded from precentral cortex of no-
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nepileptic monkeys. In addition, the cross-correlation histogram would infer that units 1 and 2 are probably receiving some common synaptic inputs or may have some intercortical connections. In either event, because both units were recorded through the same electrode, it is very likely they were close enough to be within the same cortical column. To summarize the above findings, both units appear to share some common afferent synaptic activity because they often hre within 1 ms of each other,
FIG 1. Interspike interval (ISI) and cross-correlation histograms from two precentral neurons recorded simultaneously through the same electrode within a chronic epileptogenic focus of a monkey. All ISI histograms consist of all ISIS between I and I SO ms during a 5-min behavioral period. All ISI histograms have a 2-ms bin width and cross-correlation histograms show the firing of unit 2 13 ms before and after the firing of unit I; bins are 1 ms. A-preconditioning period. R-first operant period. C-first time-out period. D-second operant period. See text for further information.
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and this tendency increased as the monkey was reinforced to lire unit 1. The IS1 distribution of unit 1 was characteristic of normal precentral neurons whereas the IS1 histogram of unit 2 was characteristic of epileptic neurons recorded from chronic foci of monkeys. At no time did unit 1 demonstrate spontaneous burst firing similar to unit 2. This finding is similar to what has been reported previously (3), i.e., normal and epileptic neurons can be found together within the same electrode tract. But what is novel in the present analysis is the demonstration that the two units may share some synaptic influences yet tire in such decidedly different patterns. REFERENCES 1. ALLUM,J. H. J., M. C. HEPFREYMOND, ANDR. GYSIN.1982.Cross-correlation analysis of interneuronal connectivityin the motorcortexof the monkey.BruinRes. 231: 32% 334. 2. WYLER,A. R., K. J. BURCHIEL, ANDC. A. ROBBINS. 1979.Operantcontrolof precentral neuronsin monkeys:evidence againstopenloopcontrol.Brain Res 1117:29-39. 3. WYLER, A. R., ANDK. J. BLJRCHIEL. 1981.Operantwntrol of epilepticneurons in chronic foci of monkeys. Brain Res. 212: 309-329. 4. WYLER, A. R 1983.Intemeuronal synchrony in pmcentral cortexof monkeys duringoperant wnditioning.Exp. Neural. 80: 697-707.