Journal of Neurophysiology

Lopez-Barneo, J.; Llinas, R.

doi: N/Apmid: 3171663

Abstract 1. The electrophysiologic properties and ionic conductances of neurons located in the stratum griseum medium (SGM) of the guinea pig superior colliculus (SC) were studied by intracellular techniques in an in vitro mesencephalic slice preparation. 2. Cells were stained with Lucifer yellow and demonstrated a uniform appearance. They had an ovoid soma with dendrites directed toward the dorsal surface. These dendrites crossed the stratum opticum, and their fine ramifications reached the stratum zonale. 3. SGM cells had a mean resting potential of 59.4 +/- 5.1 (SE) mV (n = 30), a mean slope input resistance of 26.6 +/- 10 M omega (n = 30), and a mean time constant of 4.13 +/- 1.3 ms (n = 27). 4. Direct depolarization of SC neurons produced tonic repetitive firing. These Na+-dependent action potentials showed spike-frequency adaptation. After addition of tetrodotoxin (TTX) and replacement of Ca2+ by Ba2+, slow, high-threshold spikes were also generated. The trains of Ba2+ spikes did not show adaptation. 5. In about half of the cells direct hyperpolarization elicited a slow return of the membrane potential to base line at the termination of the pulse (probably due to activation of an A-type conductance) and no anomalous rectification. The remaining cells did not have an A-type conductance but demonstrated anomolous rectification which was reversibly abolished by Cs+ but unaffected by Ba2+. 6. Some cells could be anti- and/or orthodromically activated by a stimulating electrode placed at the intercollicular commissure. These, and action potentials elicited by direct activation, had a shoulder on their falling phase. The shoulder disappeared after removal of external Ca2+ or addition of Cd2+ to the bath. 7. During repetitive firing in those cells that demonstrated an A-type conductance, the shoulder became progressively more accentuated during the train of spikes, due to inactivation of this A-type conductance. This resulted in an increase in spike duration. 8. The electrophysiological properties of these cells and their morphological characteristics suggest that they may serve as the element integrating visual and nonvisual information at the superior colliculus. Copyright © 1988 the American Physiological Society

Berger, T. W.; Eriksson, J. L.; Ciarolla, D. A.; Sclabassi, R. J.

doi: N/Apmid: N/A

Abstract 1. Nonlinear systems analytic techniques were used to characterize transformational properties of the network of neurons activated by perforant path input to the rabbit hippocampus. Trains of 4,064 impulses with randomly varying interimpulse intervals were used to stimulate perforant path fibers, and amplitudes of evoked dentate granule cell population spikes were measured. Interimpulse intervals of the random stimulus train were determined by a Poisson distribution with a mean interimpulse interval of 500 ms, and with intervals ranging from 1 to 5,000 ms. The response of dentate granule cells to this stimulation was assumed to reflect activity in the larger hippocampal network, because other subpopulations of neurons activated monosynaptically and polysynaptically within the hippocampal formation contribute to granule cell excitability through multiple feedforward and feedback pathways. System properties were characterized both for halothane anesthetized and chronically implanted, unanesthetized preparations. 2. Second-order kernel analysis showed that population spike amplitude was highly dependent on interimpulse interval. When population spikes of all latencies were included in the same analysis, stimulation impulses produced near-total suppression of spike amplitude when they were preceded 10-20 ms by another impulse in the train. Spike suppression extended to approximately 50 ms and was inversely related to length of the interimpulse interval. Suppression of granule cell response to intervals within the range of 10-50 ms was not influenced by halothane anesthesia. 3. Interstimulus intervals greater than approximately 50 ms resulted in a facilitation of population spike amplitude, with maximum facilitation occurring in response to intervals of 90-100 ms. The magnitude of maximum facilitation was significantly greater for anesthetized (129%) than for unanesthetized (74%) preparations. The range of intervals resulting in facilitation for unanesthetized animals could extend to 1,000-1,100 ms (average range, 61-714 ms). This was much greater than observed for population spikes recorded from anesthetized animals (50-364 ms), which exhibited suppression in response to intervals of approximately 300-700 ms. 4. Further analysis revealed that the nature of nonlinearities in population spike amplitude may depend on spike latency. For example, population spikes of "short" latency (3-4 or 4-5 ms, depending on the animal) exhibited only facilitation in response to interstimulus intervals of 1-4 ms.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

McCue, M. P.; Guinan, J. J.

doi: N/Apmid: 3171662

Abstract 1. Electromyographic activity (EMG) is detectable in the feline stapedius muscle 6-10 ms after the onset of an intense sound presented to either ear. Stapedius reflexes evoked by ipsilateral and contralateral sound were measured electromyographically before and after brain stem lesions were made. In some cases, stapedius motor axons were cut; in others, brain stem regions containing motoneuron cell bodies were destroyed electrolytically. 2. Electrolytic lesions that contacted an anatomically separate cluster of stapedius motoneurons (the ventromedial perifacial group) greatly reduced responses to contralateral sound without noticeably affecting responses to ipsilateral sound. 3. Electrolytic lesions in other brain stem areas had different effects; one appeared to reduce responses to ipsilateral sound selectively, whereas others reduced both responses or had little effect. 4. After subsets of stapedius motor axons were cut at the facial colliculus in the floor of the fourth ventricle, responses to contralateral sound were almost eliminated, while substantial responses to ipsilateral sound remained. 5. The results are consistent with the hypothesis that inputs from the two cochleas are distributed inhomogeneously across the stapedius motoneuron pool in such a way as to produce a segregation of function, with motoneurons in one brain stem region responding preferentially (or exclusively) to contralateral sound and motoneurons in other regions responding preferentially (or exclusively) to ipsilateral sound. This topographic organization of acoustic input to the stapedius motoneuron pool produces a "central partitioning" in the acoustic stapedius reflexes similar in some respects to the partitioning observed in proprioceptive spinal reflexes. Copyright © 1988 the American Physiological Society

Abeles, M.; Gerstein, G. L.

doi: N/Apmid: 3171666

Abstract 1. A particular firing pattern among simultaneously observed neurons represents a particular sequence of activity. If any multineuron pattern repeats significantly more than expected by chance, we may be observing a repeated state of a neural assembly as it processes similar units of information. 2. We present here an algorithm that rapidly finds all single or multineuron patterns that repeat two or more times within a block of data, as well as equations for calculating the number of patterns of given length and repetition that would be expected. The complexity of patterns for which it is practical to compute expected numbers is three to six spikes (inclusive). 3. Confidence limits are based on these expected numbers of patterns, so that is possible to identify groups of patterns that are worthy of further analysis. 4. These methods are tested against simulated multineuron data that has various types of known nonstationarities, with good agreement between observed and expected values. 5. Application to real spike trains shows a large excess of observed repeating patterns, of which some, but not all, are shown to be due to bursts of high frequency firing. 6. It should be possible to apply the new method as a filter in real time in order to search for an association between repeated pattern events and externally observable events (stimulus, behavior, etc.). Any repeated pattern events which cannot be so associated may represent a new indicator of internal events in the nervous system. Copyright © 1988 the American Physiological Society

Arkin, M. S.; Miller, R. F.

doi: N/Apmid: 3171661

Abstract 1. Sustained ON-ganglion cells from the mudpuppy retina were studied with a combined approach, including intracellular and extracellular recording from the superfused retina-eyecup preparation, pharmacology with bath-applied 2-amino-4-phosphonobutyrate (APB), and retrograde and intracellular staining using horse radish peroxidase (HRP). 2. Bath application of micromolar levels of APB selectively blocks the light response of ON-bipolar cells; APB was used to separate synaptic inputs into those which originate from ON- vs. OFF-bipolar cells. This approach clearly demonstrates that the light response of the vast majority of sustained ON-ganglion cells is primarily the result of sustained excitatory inputs that arise (directly or indirectly) from ON-bipolar cells. 3. APB revealed the presence of transient excitatory OFF-inputs in many sustained ON-ganglion cells that are normally not evident. 4. Five sustained ON-ganglion cells were intracellularly stained with HRP and their morphology was analyzed with the aid of a computer-assisted neuron reconstruction system. The stained cells are anatomically similar, based on quantitative analysis of a number of morphological parameters. The dendritic trees of all five cells are primarily confined to sublamina b of the inner plexiform layer, although some cells have a small number of processes that ramify in sublamina a. These latter processes may relate to the transient excitatory OFF-inputs revealed with APB application. 5. Ganglion cells which are morphologically similar to the stained, intracellularly sustained ON-ganglion cells were found in a collection of Golgi-like cells that were labeled by retrograde HRP transport. This raises the possibility that sustained ON-ganglion cells in the mudpuppy may constitute a morphologically identifiable class of retinal ganglion cells in this species. There is also some suggestion that a morphologically similar class of OFF-cells may be present. Copyright © 1988 the American Physiological Society

Knapp, A. G.; Ariel, M.; Robinson, F. R.

doi: N/Apmid: 3171653

Abstract 1. Horizontal optokinetic nystagmus (OKN) was examined in alert rabbits and cats following intravitreal injection of 2-amino-4-phosphonobutyrate (APB), an agent which selectively blocks the light-responsiveness of retinal ON-cells while having little effect on OFF-cells. The retinal actions of APB were assessed independently by electroretinography. 2. In five rabbits, doses of APB sufficient to eliminate the b-wave of the electroretinogram reduced drastically the ability of the injected eye to drive OKN at all stimulus speeds tested (1-96 degrees/s). Impairment of OKN was apparent within minutes of the injection, remained maximal for several hours, and recovered completely in 1-7 days. OKN in response to stimulation of the uninjected eye alone remained qualitatively and quantitatively normal. 3. Following administration of APB, OKN in response to binocular stimulation displayed a directional asymmetry. Stimuli moving in the preferred (temporal-to-nasal) direction for the uninjected eye became more effective than stimuli moving in the opposite direction, indicating that the injected eye could no longer contribute to binocular OKN. 4. When rabbits viewed stationary stimuli through the APB-treated eye alone, episodes of slow (less than 1 degrees/s) ocular drift were observed, similar to the positional instability seen when rabbits are placed in darkness or when the retinal image is stablized artifically (12). 5. APB had little effect on OKN in normal cats. In two cats that had previously received large lesions of the visual cortex, however, APB eliminated the ability of the injected eye to drive monocular OKN. The extent of the impairment was similar to that seen in rabbits. Because the cortex is thought to contribute more to OKN in cats than in rabbits, this result suggests that the optokinetic pathways disrupted by APB project subcortically. 6. This study demonstrates that the integrity of retinal ON-cells is required to sustain normal OKN. The results are consistent with additional anatomic and physiological evidence suggesting that a particular subclass of retinal ganglion cells, the ON-direction-selective cells, may provide a crucial source of visual input to central optokinetic pathways. Copyright © 1988 the American Physiological Society

Llinas, R.; Lopez-Barneo, J.

doi: N/Apmid: 3171664

Abstract 1. The long-term adaptation of repetitive firing in guinea pig superior colliculus neurons was studied in a mesencephalic slice preparation using intracellular recording techniques. 2. This long-term adaptation was characterized by a decrease in the number of action potentials generated by a depolarizing pulse of constant amplitude applied at frequencies of 0.5-2 Hz. Long-term adaptation appeared in all cells tested regardless of whether they showed short-term spike frequency adaptation during each pulse. 3. Long-term adaptation had a close-to-exponential time course with a time constant of 4.085 +/- 0.675 s (mean +/- SD, n = 8). This phenomenon developed more rapidly as the stimulus frequency increased and was paralleled by a progressive hyperpolarization of the membrane potential which, at the termination of the train of stimuli, remained 6-10 mV more negative than the resting value. 4. The hyperpolarization and the spike frequency adaptation recovered spontaneously in approximately 60 s. The time constant of recovery was 14.66 +/- 1.189 s (n = 4). 5. The afterhyperpolarization (AHP) was also paralleled by a decrease in the input resistance of the cells. This response and the adaptation disappeared after removal of Ca2+ or after addition of Cd2+ to the external solution. This suggests that Ca2+ entry during trains of action potentials activates a Ca2+-dependent K+ conductance with an unusually slow kinetics. 6. This conductance appears to differ from other Ca2+-dependent K+ conductances in that it was blocked by 4-aminopyridine. 7. The properties of this long-term adaptation are remarkably similar to those reported for visual habituation; thus this newly described K+ conductance may be pertinent to the understanding of this behavioral phenomenon. Copyright © 1988 the American Physiological Society

Bindman, L. J.; Murphy, K. P.; Pockett, S.

doi: N/Apmid: 2845015

Abstract 1. Long-term potentiation (LTP) is an enduring, activity-induced increase in the efficacy of synaptic transmission, which has been considered as a possible neural substrate for learning. Recent experiments have shown that LTP can be induced in hippocampal CA1 neurons when a presynaptic volley is paired repetitively with depolarization of the postsynaptic cell, brought about with intracellularly applied depolarizing current pulses (20, 33). We have repeated these experiments in neocortical neurons, in transverse slices of rat sensorimotor cortex in vitro. 2. Stable intracellular recordings were obtained from 28 neurons (mean resting potential -78 mV, mean spike amplitude 95 mV, mean input resistance 41 M omega) mostly in layers V and VI. Two different afferent pathways were stimulated alternately at 0.2 Hz to evoke subthreshold composite excitatory postsynaptic potentials (EPSPs). One micromolar bicuculline methiodide was added to the bathing medium in most experiments. 3. Repetitive pairing of one afferent volley with a coincident intracellular depolarizing current pulse (100-200 ms long) of a magnitude sufficient to make the neuron fire 6 to 13 action potentials/pulse, gave rise after 30-50 pairings in 4 neurons to a significant enduring increase in the amplitude of the paired EPSP. The increase persisted without decrement for as long as the recording continued (range 15-50 min after the pairing ended) but the amplitude of the unpaired EPSP was unchanged. During the LTP, the membrane potential and the apparent input resistance of the postsynaptic neurons were also unchanged. 4. In two cells a significant prolonged depression of the paired EPSP was induced while the unpaired EPSP was unaffected. Membrane potential and input resistance were not changed. In the remaining 22 cells neither the paired nor the unpaired EPSP was altered. 5. Brief, tetanic stimulation was applied to one afferent pathway in 11 of the neurons in which postsynaptic stimulation had been ineffective. A variety of effects was produced (LTP, depression, or posttetanic potentiation). All the effects of tetanic stimulation were confined to the stimulated pathway. 6. We conclude that LTP can be produced in some neocortical neurons by pairing a presynaptic volley with postsynaptic depolarization, in an experimental paradigm that conforms to Hebb's (17) model of associative conditioning. Depression of the paired EPSP was produced in other cells with the same experimental design.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Sclabassi, R. J.; Eriksson, J. L.; Port, R. L.; Robinson, G. B.; Berger, T. W.

doi: N/Apmid: 3171656

Abstract 1. Nonlinear systems analytic procedures, based on an orthogonalized functional power series approach, were developed for study of the transformational properties of the hippocampal formation. As a testing stimulus, the procedures utilize a train of electrical impulses with randomly varying interimpulse intervals. The specific case was considered of applying such a stimulus to the perforant path, a major afferent to the hippocampal dentate gyrus that arises from the entorhinal cortex. Resulting field potentials evoked within the dentate gyrus are recorded to all impulses in the train. Computational algorithms based on cross-correlations determine the relationship between the interimpulse interval within the random train and amplitude of the evoked dentate potentials. The calculations, which reduce to averaging procedures, were derived for first- and second-order terms, or kernels, of the orthogonalized functional power series. 2. It is proposed that such an approach can be applied to a single component of the complex field potential evoked in the dentate gyrus. This component, the population spike, reflects the action potential discharge of dentate granule cells. Thus, a field potential component for which the underlying neuronal generator is well-known can be analyzed with respect to the transformational characteristics of the network of neurons that influence that generator. Other components of the complex field potential produced by other generators can be ignored. It is shown that this adaptation has the effect of greatly simplifying both the computation and presentation of kernels. 3. As a further consequence of this adaptation, the resulting first- and second-order kernels were shown to have specific interpretations. The first-order kernel represents the average response of the orthodromically driven granule cells to the set of stimuli comprising the random impulse train. The second-order kernel quantitatively characterizes the nonlinearity of the granule cell response, and may be interpreted as a generalized recovery function; i.e., the first input of any pair of stimuli in the train activates the newtork, and the second input tests the modulatory influence of the network excited by the initial input. 4. Most past investigations of nonlinearities of the perforant path-dentate projection have utilized pairs of stimulus impulses. We show here that, for a second-order system, the expected results from paired impulse experiments may be predicted from second-order kernels. Disagreement between the measured and predicted results reflects interactions of a higher order, and thus, greater system complexity.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Ariel, M.; Robinson, F. R.; Knapp, A. G.

doi: N/Apmid: 3171654

Abstract 1. Eye movements were observed following an injection of picrotoxin, a GABA antagonist, into the vitreous of one eye. A spontaneous nystagmus was observed in cats, rabbits, and turtles, even in total darkness, with slow-phase eye movements in the temporal-to-nasal direction for the injected eye. 2. During visual stimulation by a horizontal drifting pattern, injected eyes moved in the temporal-to-nasal direction, irrespective of stimulus direction. In cats, however, the nystagmus was usually slower when the injected eye viewed nasal-to-temporal motion (opposite to the direction of the spontaneous nystagmus). The spontaneous nystagmus could be halted or even reversed by allowing cats to view motion opposite to the direction of the nystagmus with the uninjected eye alone. The nystagmus could not be overridden in this fashion in rabbits or turtles. 3. The nystagmus induced by picrotoxin could also be modified by vestibular stimulation. When cats were placed on their sides, the spontaneous horizontal nystagmus often decreased and spontaneous vertical nystagmus with upward slow phase movements occurred. During sinusoidal horizontal vestibular stimulation, the horizontal nystagmus due to picrotoxin added to the vestibuloocular reflex as a velocity offset in the temporal-to-nasal direction. 4. Following bilateral ablation of the cat visual cortex, picrotoxin's effect became even more pronounced than before the ablation. Therefore, at least some picrotoxin-sensitive cells can use subcortical pathways, perhaps to the accessory optic nuclei. The visual cortex, which also processes directional information, may be able to compensate for changes in retinal processing induced by picrotoxin in intact animals. 5. This study demonstrates the importance of retinal GABA in the control of eye stability. As GABA is known to be responsible for null direction inhibition of directionally sensitive retinal ganglion cells, these results suggest that the output of these cells may be critical for the normal functioning of central optokinetic pathways, even in the absence of visual cortex. Copyright © 1988 the American Physiological Society