Journal of Neurophysiology

Buchanan, J. T.; Grillner, S.; Cullheim, S.; Risling, M.

doi: N/Apmid: 2754481

Abstract 1. In the in vitro preparation of the lamprey spinal cord, paired intracellular recordings of membrane potential were used to identify interneurons producing excitatory postsynaptic potentials (EPSPs) on myotomal motoneurons. 2. Seventy-nine interneurons (8.4% of all neuron-motoneuron pairs tested) elicited unitary EPSPs that followed one-for-one at short, constant latencies and were therefore considered monosynaptic according to conventional criteria. Evidence was obtained for selectivity and divergence of excitatory interneuron (EIN) outputs and for convergence of EIN input to motoneurons. 3. The neurotransmitter released by EINs may be an excitatory amino acid such as glutamate, because the EPSPs were depressed by antagonists of excitatory amino acids. 4. Intracellular dye injection revealed that EINs have small cell bodies (average 11 x 27 microns), transversely oriented dendrites, and thin (less than 3 microns) slowly conducting axons (0.7 m/s) that project caudally and ipsilaterally. One EIN exhibited a system of thin multi-branching axon collaterals with periodic swellings. Ultrastructurally, these swellings contained clear spherical vesicles, and they apposed postsynaptic membrane specializations. 5. During fictive locomotion, the membrane-potential oscillations of EINs were greater in amplitude than, but similar in shape and timing to, those of their postsynaptic motoneurons. EINs fired action potentials during fictive locomotion and contributed to the depolarization of motoneurons. 6. These interneurons are proposed to be a source of excitation to motoneurons and interneurons in the lamprey spinal cord, participating in motor activity including locomotion. Copyright © 1989 the American Physiological Society

Yoshimura, M.; Jessell, T. M.

doi: N/Apmid: 2754464

Abstract 1. The membrane properties of substantia gelatinosa (SG) neurons in an in vitro adult rat transverse spinal cord slice preparation with attached dorsal root have been examined. Intracellular recordings were obtained from identified SG neurons. 2. Seventy-six percent of SG neurons exhibited a time-dependent anomalous rectification (AR) when the membrane was hyperpolarized from the resting potential. The time-dependent AR was blocked by cesium (Cs+, 2 mM) but not by barium (Ba2+, 2 mM). Application of Cs+ itself caused membrane hyperpolarization in those SG neurons that expressed the time-dependent AR. The activation of the time-dependent AR was maximal at potentials 5-10 mV below the resting membrane potential. 3. In a few SG neurons, the current-voltage relationship revealed a marked inward rectification, even though there was no detectable time-dependent anomalous rectification during hyperpolarization. Analysis of the Ba2+- and Cs+-sensitivity of these neurons confirmed that SG neurons expressed two distinct ARs, one of which is fast and Ba2+-sensitive and the other of which is time-dependent and Ba2+-insensitive. 4. Fifty-one percent of SG neurons exhibited a transient outward rectification when hyperpolarizing current pulses were applied from potentials more positive than -60 mV or when depolarizing pulses were applied from potentials more negative than -65 mV. The transient outward rectification persisted for 0.3-2 s when hyperpolarizing pulses were applied at -55 mV. 5. The transient outward rectification was associated with a decrease in membrane resistance and was enhanced in low K+ solutions. 4-aminopyridine (4-AP, 2 mM) reversibly blocked the transient outward rectification. 6. The time-dependent anomalous and transient outward rectifying currents exerted opposite effects on the firing properties of SG neurons. Activation of the time-dependent AR increased neuronal excitability. In neurons that exhibited the time-dependent AR, membrane depolarization caused the appearance of a rebound depolarization that resulted in the generation of spikes with only a short delay after application of the depolarizing pulse. In contrast, the transient outward rectifying current markedly delayed spike firing in response to depolarizing pulses. This delay was blocked by application of 4-AP. 7. The diversity in response properties of subpopulations of SG neurons may result in part from this heterogeneity in membrane properties. Copyright © 1989 the American Physiological Society

Mioche, L.; Singer, W.

doi: N/Apmid: 2754471

Abstract 1. With the use of chronically implanted floating microelectrodes, we obtained simultaneous single-unit recordings from multiple sites in the kitten striate cortex and followed experience-dependent modifications of receptive-field properties. For induction of experimental modifications, we used the paradigm of monocular deprivation and reverse occlusion. Kittens were implanted when 4-5 wk old. During the following 2 days, receptive-field properties of the recorded units were determined once under light ketamine anesthesia and repeatedly while the kittens were awake and only lightly restrained. Subsequently, one eye was patched, and the resulting changes in neuronal eye preference were followed by repeated measurements of response properties. For investigation of the effects of reverse occlusion, the deprived eye was opened and the previously open eye closed when the neurons had become unresponsive to the initially deprived eye. Alternatively, kittens were monocularly deprived for 1 wk by lid suture before implantation. The closed eye was then opened, the other eye patched, and the effects of reverse occlusion were studied for up to 1 wk by repeated measurements of receptive-field properties. 2. The earliest effect of monocular deprivation was the disappearance of binocular summation, i.e., binocular responses ceased to be superior over monocular responses. Overt changes of ocular dominance were observed as early as 6 h after the beginning of monocular deprivation. These consisted of a gradual decrease of the excitatory response to deprived eye stimulation and, on occasions, of an additional moderate increase of responses to the normal eye. A complete loss of excitatory responses to deprived-eye stimulation was seen as early as 12 h after occlusion. In numerous cells, however, stimulation of the deprived eye continued to evoke inhibitory responses even after excitatory responses had vanished completely. During this shift in ocularity, neurons preserved their orientation and direction selectively. 3. The minimal time required for the manifestation of ocular dominance changes was similar regardless of whether the animals were stimulated continuously or were asleep part of the time, suggesting the existence of an experience-independent consolidation period for ocular dominance changes. 4. The first change after reverse occlusion was a reduction of the response to the newly deprived eye. The time course of this inactivation was similar to that observed after initial deprivation, whereas the recovery of responses to the previously deprived eye had a considerably slower time course.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1989 the American Physiological Society

Ness, T. J.; Gebhart, G. F.

doi: N/Apmid: 2547035

Abstract 1. The effect of morphine or clonidine administered systemically on visceral and cutaneous spinal nociceptive transmission was examined in 45 dorsal horn neurons in spinalized, decerebrate rats: 17 "cutaneous" dorsal horn neurons located in the L3-L5 spinal segments were excited by heating the glabrous skin of the hindpaw (48 degrees C, 15 s) and 28 "visceral" dorsal horn neurons located in the T13-L2 spinal segments were excited by colorectal distension (80 mmHg, 20 s). The 28 visceral dorsal horn neurons were subclassified as 18 short-latency abrupt neurons (SL-A), which were excited by colorectal distension at short latency (less than 1 s) and whose activity abruptly returned to base line following termination of the distending stimulus, and as 10 short-latency-sustained (SL-S) neurons, which also were excited at short latency (less than 1 s) by colorectal distension, but whose activity was sustained above base line for 4-31 s following termination of the distending stimulus. 2. Morphine produced a dose-dependent, naloxone-reversible inhibition of both spontaneous activity and/or neuronal responses during heating or colorectal distension of 8 SL-A, 7 SL-S, and 11 cutaneous dorsal horn neurons. Comparison of the effective doses of morphine to produce a 50% reduction in the response of the neurons (ED50s) during colorectal distension or heating demonstrated that, at the intensities of distension and heating employed, SL-S neurons were affected at the least dosage (ED50 = 0.46 mumol/kg), followed by SL-A neurons (ED50 = 1.95 mumol/kg) and cutaneous neurons (ED50 = 6.12 mumol/kg). Effects on spontaneous activity were variable: at low doses morphine produced an increase in the spontaneous activity of 2 SL-A and 5 cutaneous neurons; greater doses (up to 42 mumol/kg) inhibited in all of the SL-A and SL-S neurons, but not three cutaneous neurons studied. With the exclusion of these three neurons, the ED50s for inhibition of spontaneous activity were comparable to the ED50s for inhibition of neuronal responses during colorectal distension or heating of the hindpaw in all three neuronal groups. 3. Clonidine produced a dose-dependent, yohimbine- or phentolamine-reversible inhibition of both spontaneous activity and neuronal responses during heating or colorectal distension of 10 SL-A, 3 SL-S, and 6 cutaneous dorsal horn neurons.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1989 the American Physiological Society

Stringer, J. L.; Williamson, J. M.; Lothman, E. W.

doi: N/Apmid: 2754466

Abstract 1. Electrical-stimulus trains activated hippocampal circuits in urethan-anesthetized rats. Responses were monitored with recordings of extracellular potentials and with measurements of the extracellular potassium (K+o). Stimulating electrodes were placed in the CA3 region contralateral to the recording electrode (cCA3) and in the ipsilateral angular bundle (AB) while recording in the CA1 pyramidal-cell layer or the granule-cell layer of the dentate gyrus. Patterns of maximal activation were identified. 2. In the CA1 region, maximal activation was indicated by the presence of 10- to 15-mV population spikes, a smooth rise in K+o of 5-6 mM above base-line levels of 3 mM, and a negative shift of the sustained DC potential of 2-4 mV. The dentate gyrus was considered to be maximally activated when bursts of large-amplitude (20-40 mV) population spikes were present. These population spikes were associated with a secondary rise in K+o to 6-8 mM above base line and an abrupt negative shift of the DC potential of 5-8 mV. 3. Maximal activation depended on the stimulus intensity, frequency, and duration. Trains of 10-Hz stimuli were used to determine the lowest stimulus intensity needed to elicit complete activation in CA1 and in the dentate gyrus. At this intensity, afterdischarges were not produced, and these responses could be elicited repeatedly. 4. By the use of this threshold stimulus intensity, cCA3 stimulation produced a rapid and progressive augmentation of CA1 responses until maximal activation was reached. In comparison, stimulation of the AB could produce the same end result, but the appearance of CA1 population spikes was delayed. Stimulation of the AB produced a steady increase in the evoked granule-cell population spike until the appearance of the paroxysmal large-amplitude population spikes. In contrast, cCA3 stimulation produced two positive evoked responses in the dentate gyrus before the paroxysms of population spikes began. 5. The frequency dependence of the responses was determined by giving stimulus trains ranging from 2 to 100 Hz. Stimulation of cCA3 produced population spikes in CA1 up to 100 Hz that were all associated with the same peak rise in K+o. AB stimulation only produced CA1 responses with stimulation frequencies between 15 and 25 Hz. The paroxysmal dentate population spikes were generated by stimulus frequencies between 15 and 30 Hz with both AB and cCA3 stimulation. 6. Unilateral colchicine injections caused a loss of dentate granule cells and a loss of maximal dentate activation on the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1989 the American Physiological Society

Koshland, G. F.; Smith, J. L.

doi: N/Apmid: 2754470

Abstract 1. Hindlimb paw-shake responses were assessed before and after unilateral deafferentation (L3-S1) in chronic-spinal cats (n = 5), spinalized at the T12 level 1 yr earlier. Selected ankle flexor tibialis anterior (TA) and extensor lateral gastrocnemius (LG) and knee extensor vastus lateralis (VL) muscles were surgically implanted with chronic electromyographic (EMG) electrodes to determine mutable features of cycle characteristics and muscle synergies that are modulated by motion-dependent feedback as opposed to immutable features that are centrally programmed and not modulated by limb afference. 2. Paw-shake responses were difficult to elicit in the extensively deafferented hindlimb; this was true particularly during the first recovery weeks after deafferentation. By the end of the first month, however, brief responses of 1 or 2 cycles were commonly elicited in four of five cats, and responses of 3-7 cycles were common by the end of the second month in three of five cats. Initially, responses in the deafferented limb were elicited by stimuli applied to the dorsolateral thigh, an oval patch of skin innervated by intact S2 afferents. Over the 4-mo recovery period, however, the receptive field of the largely denervated skin expanded, and responses were also elicited by stimuli applied to the lateral aspect of the knee and shank, but usually not the paw. 3. In addition to fewer average cycles per response (5 vs. 10 cycles), paw shaking evoked in the deafferented hindlimb was characterized by longer-than-average cycle periods (124 vs. 98 ms), but the average cycle period varied widely among responses, ranging from 99 to 239 ms. Before deafferentation, the temporal organization of consecutive cycles was stereotypic; cycle periods increased linearly throughout a response. After deafferentation, however, there was no systematic relationship between cycle period and cycle number, and approximately 14% of the records with greater than or equal to 3 cycles were characterized by arhythmical sequences of EMG bursts. 4. At the ankle, LG burst duration was not altered by deafferentation, but TA onset and burst duration were affected. Before deafferentation, TA onset was invariant with respect to the beginning of the cycle, and burst duration increased linearly with cycle period. After deafferentation, however, TA onset was delayed, and the delay increased linearly with cycle period. Consequently, the TA burst duration was brief and unrelated to cycle period.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1989 the American Physiological Society

Grossman, G. E.; Leigh, R. J.; Bruce, E. N.; Huebner, W. P.; Lanska, D. J.

doi: N/Apmid: 2754477

Abstract 1. The stability of gaze was measured in nine normal subjects during 30-s epochs of standing, walking in place, and running in place. The angle of gaze and head rotations in horizontal and vertical planes were measured using the magnetic search coil technique. Subjects visually fixed on a stationary object located at a distance of 100 m; thus measurements of gaze indicated the stability of images on the retina. 2. During standing, walking, or running in place, the standard deviation of the angle of gaze was less than 0.4 degrees, both horizontally and vertically. During standing and walking in place, peak gaze velocity (Gp) was less than 3.0 degrees/s. During running in place, Gp was less than 3.0 degrees/s horizontally but ranged up to 9.3 degrees/s vertically. 3. Visual acuity was measured during standing, walking, and running in place. During walking in place, five of nine subjects showed a small but significant (P = 0.03) decline in visual acuity compared with standing. During running in place, all nine subjects showed a small but significant (P = 0.002) decline in visual acuity compared with standing. 4. Stability of gaze was also measured during vigorous, voluntary head rotations in the horizontal (yaw) or vertical (pitch) planes, for 15-s epochs. Gp ranged as high as 70 degrees/s horizontally and 41 degrees/s vertically. All subjects reported illusory movement of the seen environment during these head rotations. 5. The suitability of linear systems techniques for analysis of the horizontal and vertical vestibuloocular reflex (VOR) during walking and running in place was assessed using coherence spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS) Copyright © 1989 the American Physiological Society

Leblond, J.; Krnjevic, K.

doi: N/Apmid: 2547034

Abstract 1. Reversible effects of brief periods of anoxia (replacing 95% O2-5% CO2 with 95% N2-5% CO2 for 2-4 min) were studied in CA1 neurons in hippocampal slices (from Sprague-Dawley rats), kept in an interface-type chamber at 33.5 degree. 2. The predominant voltage change during anoxia (N2) was a hyperpolarization, accompanied by a marked fall in resistance and excitability; synaptic potentials were also depressed, especially inhibitory postsynaptic potentials (IPSPs). 3. In voltage-current (V-I) plots, the N2-evoked hypolarization had a reversal potential below -90mV, even when recording with 2 M KCl electrodes and after substituting 90% of medium Cl- with isethionate. The accompanying fall in input resistance (RN) is therefore probably caused by an increase in K conductance (in agreement with previous reports). There was evidence that anomalous rectification enhances the fall in RN but limits the hyperpolarization. 4. These effects of anoxia were not fully blocked by any of the K-channel antagonists tested, including Cs, TEA, 4-AP, quinine and apamin. 5. Intracellular injections of Ca chelators caused a variable depression of N2-evoked reductions in RN. 6. It is unlikely that N2 activates ATP-sensitive K channels as tolbutamide enhanced rather than depressed the hyperpolarization and fall in RN. 7. When early depletion of cellular ATP was prevented by incubation in creatine (25 mM for greater than 1 h), even longer anoxic periods produced only minor changes in potential, RN, and synaptic transmission. 8. It was concluded that activation of K conductance by a rise in cytosolic-free Ca2+ is the most plausible of several possible underlying mechanisms. Copyright © 1989 the American Physiological Society

Poulter, M. O.; Hashiguchi, T.; Padjen, A. L.

doi: N/Apmid: 2787843

Abstract 1. Intracellular microelectrode recordings from large sensory and motor myelinated axons in spinal roots of Rana pipiens were used to study the effects of dendrotoxin (DTX), a specific blocker of a fast activating potassium current (GKf1). 2. Dendrotoxin reduced the ability of myelinated sensory and motor axons to accommodate to a constant stimulus. A depolarizing current step, which normally evoked only one action potential, after dendrotoxin treatment (200-500 nM) produced a train of action potentials. These spike trains lasted 29 +/- 2.8 (SE) ms on average in sensory fibers (n = 18) and 40.2 +/- 4.5 ms in motor fibers (n = 9). 3. After dendrotoxin treatment, in addition to a reduction in the ability to accommodate to a constant stimulus, a slowing in the rate of action potential generation was evident (spike frequency adaptation). 4. Dendrotoxin had no effect on the rising phase of conducted action potentials evoked by peripheral stimulation. Together with a lack of effect on the absolute refractory period, these results indicate that dendrotoxin does not affect sodium channel activity. 5. The steady-state voltage/current relationship was unchanged in response to hyperpolarizing current pulses; however, there was a significant increase in cord resistance in response to depolarizing current steps, demonstrating that DTX decreases outward rectification. 6. A computer model based on Hodgkin and Huxley equations was developed, which included the three voltage-dependent potassium conductances described by Dubois. The model reproduced major experimental results: removal of the conductance, termed GKf1, reduced the accommodation in the early phase of a continuous stimulus, indicating that this current could be responsible for the early accommodation. The hypothesis that the slow potassium conductance GKs regulates late accommodation and action potential frequency adaptation is also supported by the computer model. 7. In summary, these results suggest that in amphibian myelinated sensory and motor axons, the activity of potassium conductances can account for accommodation and adaptation without involvement of sodium conductance activity. Copyright © 1989 the American Physiological Society

Gamlin, P. D.; Gnadt, J. W.; Mays, L. E.

doi: N/Apmid: 2754483

Abstract 1. To characterize the vergence signal carried by the medial longitudinal fasciculus (MLF), it was subjected to reversible blockade by small injections of 10% lidocaine hydrochloride. The effects of these blockades on both conjugate and vergence eye movements were studied. 2. With this procedure, experimentally induced internuclear ophthalmoplegia (INO) and its effects on conjugate eye movements could be studied acutely, without possible contamination from long-term oculomotor adaptation. In the eye contralateral to the MLF blockade, saccadic and horizontal smooth-pursuit eye movements were normal. Horizontal abducting nystagmus, often seen in patients with INO, was not observed in this eye. 3. As previously reported for INO, profound oculomotor deficits were seen in the eye ipsilateral to the MLF blockade. During maximal blockade, adducting saccades and horizontal smooth-pursuit movements in this eye did not cross the midline. Adducting saccades were reduced in amplitude and peak velocity and showed significantly increased durations. Abducting saccades, which were slightly hypometric, displayed a marked postsaccadic centripetal drift. 4. The eye ipsilateral to the blockade displayed a pronounced, upward, slow drift, whereas the eye contralateral to the blockade showed virtually no drift. Furthermore, although vertical saccades to visual targets remained essentially conjugate, the size of the resetting quick phases in each eye was related to the amplitude of the slow phase movement in that eye. Thus the eye on the affected side displayed large quick phases, whereas the eye on the unaffected side showed only slight movements. On occasion, unilateral downbeating nystagmus was seen. This strongly suggests that the vertical saccade generators for the two eyes can act independently. 5. The effect of MLF blockade on the vergence gain of the eye on the affected side was investigated. As a measure of open-loop vergence gain, the relationship of accommodative convergence to accommodation (AC/A) was measured before, during, and after reversible lidocaine block of the MLF. After taking conjugate deficits into account, the net vergence signal to the eye ipsilateral to the injection was found to increase significantly during the reversible blockade. 6. The most parsimonious explanation for this increased vergence signal is suggested by the accompanying single-unit study. This study showed that abducens internuclear neurons, whose axons course in the MLF, provide medial rectus motoneurons with an appropriate horizontal conjugate eye position signal but an inappropriate vergence signal. Ordinarily, this incorrect vergence signal is overcome by another, more potent, v Copyright © 1989 the American Physiological Society