Journal of Neurophysiology

Dougherty, P. M.; Palecek, J.; Paleckova, V.; Willis, W. D.

doi: N/Apmid: 7823080

Abstract 1. Activation of neurokinin receptors contributes to the excitation of many dorsal horn neurons by cutaneous sensory stimuli, particularly noxious stimuli. In the present study we investigate the role of neurokinin receptors in the activation of primate spinothalamic tract (STT) neurons by cutaneous mechanical stimuli and by intradermal injection of capsaicin. This was done by testing the responses of these neurons to a battery of cutaneous stimuli before and during infusion by microdialysis of antagonists selective for NK1 and NK2 receptors. 2. The NK1 receptor antagonists cis-3-(2-methoxybenzyl-amino-2-benzhydrylquinuclidine (CP96345) and D-Pro9-Spiro-y-lactam-Leu10,Trp11)-Physalaemin(1-11) (GR82334) did not significantly reduce the responses of STT cells to mechanical stimulation of the skin. Both NK1 antagonists did, however, produce a significant reduction in the responses of STT neurons to an intradermal injection of capsaicin. Finally, despite having no effects on responses to mechanical stimuli, both NK1 antagonists prevented the sensitization of the responses to cutaneous stimuli that is usually observed after intradermal injections of capsaicin. 3. The NK2 selective antagonists PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (GR98400) and Tyr5,D-Trp6,8,9,Lys10-NKA (4–10) (MEN10376) had effects very similar to those of the NK1 antagonists, but with an important difference. Neither NK2 antagonist affected the responses of STT neurons to noxious or innocuous mechanical stimulation of the skin, but they did reduce the responses to intradermal capsaicin injections. These compounds failed to prevent capsaicin-induced sensitization. In fact, cells exposed to GR98400 or MEN10376 showed unusually sustained increases in the responses to mechanical stimuli after the first capsaicin injection, suggesting that these compounds actually induced sensitization. 4. These results support the contention that both neurokinin receptors participate in the processing of nociceptive information in the dorsal horn, especially responses to strong stimuli such as intradermal injection of capsaicin. NK1 receptors are also involved in the sensitization of STT neurons after peripheral injury. A clearer understanding of the role of NK2 receptors in sensitization requires further studies with improved antagonists. Copyright © 1994 the American Physiological Society

Sutor, B.; Hablitz, J. J.; Rucker, F.; ten Bruggencate, G.

doi: N/Apmid: 7823100

Abstract 1. Adult rats and rats with a postnatal age of 3–29 days (PN 3–29) were used for the preparation of in vitro slices of the frontal neocortex. Epileptiform activity was induced by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonists bicuculline or picrotoxin. 2. The voltage-sensitive dye RH 414 and a laser scanning microscope were used for multiple-site optical recordings of membrane potential changes associated with epileptiform activity. Optical signals were compared with simultaneously measured extra-cellular field potentials. 3. Optical signals could be reliably recorded for the duration of the experiments (2–4 h). Extracellular recordings of convulsant-induced paroxysmal depolarizing shifts (PDSs) in slices stained with RH 414 were comparable with those obtained in unstained slices. Changes in dye signals in response to reductions in extracellular calcium, addition of tetrodotoxin (TTX), or application of excitatory amino acid receptor antagonists indicate that the fluorescence changes correlate well with established electrophysiological measures of epileptiform activity. 4. In slices from adult animals, dye signals were observed at all recording sites. The response with the shortest latency occurred invariably at the site of stimulation, and activity spread rapidly in both vertical and horizontal directions. Spread was significantly faster in the vertical than in the horizontal direction. 5. Epileptiform activity was absent or only weakly expressed in slices from PN 3-9 animals. Activity was detectable predominantly in upper cortical layers. 6. Dye signals were observed at all measurement points in slices from PN 10–19 animals. In this age group, peak amplitude increased with spread of activity from lower to upper cortical layers. There was no significant difference between the speed of propagation in the vertical and in the horizontal directions. Spontaneous epileptiform activity occurred at a high rate in the PN 10–19 age group, and signals associated with spontaneous epileptiform events were largest in upper layers. 7. In the PN 10–19 age group, optical signals were characterized by the repetitive occurrence of PDS discharges superimposed on a sustained response. The amplitude of the sustained response decreased with increasing distance from the site of stimulation. Analysis of the latencies revealed that the superimposed PDS-like events were generated at multiple sites within the scanning area. Amplitude and rate of rise were largest in slices from PN 10–19 animals. These values declined with ongoing development.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1994 the American Physiological Society

Church, P. J.; Lloyd, P. E.

doi: N/Apmid: 7823102

Abstract 1. The firing patterns of 22 motor neurons were determined by simultaneously recording intracellularly from up to 7 neurons during evoked feedinglike buccal motor programs (BMPs). Intracellular stimulation of cerebral-buccal interneuron 2 (CBI-2) or tactile stimulation of the odontophore were used to elicit BMPs in a reduced preparation. 2. Evoked BMPs were identified as either ingestive-like (iBMP) or egestive-like (eBMP) on the basis of their similarity to those previously recorded in select neurons in freely behaving animals. Neurons were divided into the p-group, r-group, or c-group, on the basis of the phase relationships of rhythmic membrane depolarizations and hyperpolarizations during evoked BMPs. Depolarization of the p-, r-, and c-group neurons was associated with radular protraction, retraction, and closure, respectively. With one exception, the motor neurons segregated into the same groups during iBMPs and eBMPs. The exception, B7, was categorized as a c-group neuron during iBMPs, but as an r-group neuron during eBMPs. 3. Every motor neuron exhibited cyclic membrane depolarizations and hyperpolarizations, and over one-half of the neurons fired bursts of action potentials, during both iBMPs and eBMPs. The neurons fired in patterns that would be likely to release both their conventional and peptide transmitters. 4. A marked hyperpolarizing step in the p-group neurons coincident with a depolarization in the r-group neurons was observed during both iBMPs and eBMPs, suggesting a degree of shared premotor circuitry for the two BMPs. 5. A shift in the timing of activity in c-group neurons relative to that in p- and r-group neurons during iBMPs and eBMPs was observed and correlates well with the shift in phase of radular closure relative to protraction and retraction, which is useful in distinguishing ingestion from egestion in the behaving animal. 6. The firing patterns recorded in neurons that innervate overlapping populations of muscle fibers suggested that there would be complex interactions of multiple transmitters. This is particularly intriguing in the case of I3a muscle fibers, which are innervated by two excitatory and one inhibitory neuron. The firing patterns recorded in these neurons suggest that the inhibitory motor neuron may serve to not only block inappropriate contractions, but also to specifically shape evoked contractions during feeding. Copyright © 1994 the American Physiological Society

Vivaldi, E. A.; Ocampo, A.; Wyneken, U.; Roncagliolo, M.; Zapata, A. M.

doi: N/Apmid: 7823099

Abstract 1. Sixteen rats were recorded continuously for 3 days using an automated system that detected, quantified, and stored the incidence of cortical delta waves, cortical sigma spindles, hippocampal theta rhythm, and electromyographic activity. A time series then was constructed wherein 15-s epochs were ascribed to one behavioral state: wakefulness (W), quiet sleep (QS), or active sleep (AS, a state also referred to as REM sleep). From those series, AS episodes and non-AS intervals could be determined. Episodes and intervals were defined as lasting at least two epochs and the one-epoch episodes and intervals were incorporated to the ongoing state. 2. Having established the length of each AS episode and non-AS interval, pairings were made, on the one hand between episodes and their preceding intervals, and on the other, between episodes and the intervals that followed. 3. Highly significant correlations were found between the length of AS episodes and the length of the non-AS intervals that followed. Correlations were also significant when calculated separately versus the amount of QS and of W within the following interval. Correlations improved when they were performed against the log of the interval and when only intervals with a predominance of QS were selected. 4. No significant correlation was found between the length of AS episodes and the length of the preceding non-AS intervals, except for a negative one that was present only when the statistical analysis was performed in the unsmoothed array where the one-epoch episodes and intervals were preserved. 5. These results suggest that there is a short-term homeostasis operating within the spontaneous architecture of sleep in rats. This homeostatic mechanism is not manifested by the regulation of the length of AS episodes. Instead, there is a forward regulatory mechanism that, given the duration of an AS episode, permissively controls the interval that the animal may abstain from AS, and hence the timing of the triggering of a new AS episode. Copyright © 1994 the American Physiological Society

McIntosh, A. R.; Gonzalez-Lima, F.

doi: N/Apmid: 7823097

Abstract 1. The objective was to examine how opposite learned behavioral responses to the same physical tone were differentiated by the pattern of interactions between extraauditory neural regions. This was pursued using a new approach combining behavior, neuroimaging, and network analysis to integrate information about differences in regional activity with differences in the covariance relationships between brain areas. 2. A tone was used as either a Pavlovian conditioned excitor or inhibitor. Rats were conditioned with reinforced trials of a conditioned excitor (A+) intermixed with nonreinforced trials of a tone-light compound (AX-). The tone was the excitor (A+) for the tone-excitor group and was the inhibitor (X-) for the tone-inhibitor group. After conditioning, all rats were injected with 14C(U)2-fluoro-2-deoxyglucose (FDG) and presented with the same tone. 3. FDG autoradiography was used to measure regional activity and to generate interregional correlations of activity resulting from the presentation of the tone. A stepwise discriminant analysis was used to select brain regions that differentiated the excitor from the inhibitor effects. 4. Network analysis consisted of constructing an anatomic model of the brain regions, selected by the discriminant analysis, linking the regions with their known anatomical connections. Then, functional models for the tone-excitor and -inhibitor groups were constructed using structural equation modeling. Correlations of activity between regions were decomposed to calculate numerical weights, or path coefficients, for each anatomic path. These path coefficients were used to compare the interactions for the tone-excitor and -inhibitor models. 5. Regional differences in FDG uptake were found in the sulcal frontal cortex (SFC), lateral septum (LS), medial septum/diagonal band (MS/DB), retrosplenial cortex (RS), and dentate-interpositus nuclei of the cerebellum (DEN). Discriminant analysis selected three other regions that significantly discriminated the tone-excitor and -inhibitor groups: perirhinal cortex (PRh), nucleus accumbens (ACB), and the anteroventral nucleus of the thalamus (AVN). 6. Structural equation modeling identified two functional circuits that differentiated the groups. One involved the basal forebrain regions (LS, MS/DB, ACB) and the other limbic thalamocortical structures (SFC, RS, PRh, AVN). Differences in the interactions within these circuits were mainly in sign of the covariance relationships between regions, from positive for the tone-excitor model to negative path coefficients for the tone-inhibitor model. The path coefficient between the basal forebrain circuit and the limbic thalamocortical circuit showed the largest magnitude difference. This quantitative difference was mediated by a path from the MS/DB to PRh.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1994 the American Physiological Society

Hagevik, A.; McClellan, A. D.

doi: N/Apmid: 7823103

Abstract 1. Receptor blockers for inhibitory amino acids were applied to part or all of the spinal cord of larval lamprey during brain stem-initiated locomotor activity. Blocking glycinergic inhibition with strychnine applied to the entire spinal cord converted the locomotor pattern from left-right alternation to synchronous left-right bursting. The results suggest that left and right oscillators are connected by relatively strong reciprocal inhibitory (glycinergic) connections in parallel with weaker reciprocal excitatory connections. This possible organization was supported by results from a computer model consisting of left and right oscillators connected by reciprocal inhibition and excitation in parallel. In addition, the results suggest that reciprocal inhibition is not required for left-right rhythmicity but rather is involved primarily with phasing of left-right activity. 2. Locally blocking glycinergic inhibition with strychnine in the rostral spinal cord resulted in synchronous left-right burst activity in that region of the cord as well as in more caudal areas of the cord in which reciprocal inhibition should still be functional. 3. Blocking glycinergic inhibition in the caudal spinal cord converted the pattern in that region of the cord to left-right synchronous activity. The effects in the ascending direction on the burst patterns in more rostral areas of the spinal cord were less than those mentioned above in the descending direction with application of strychnine to the rostral spinal cord. 4. With glycinergic inhibition or GABAergic inhibition blocked in the entire spinal cord, stable longitudinal coupling along the spinal cord persisted. This and the neurophysiology results mentioned above suggest that the main mechanism for longitudinal coupling between locomotor networks in adjacent regions of the spinal cord is ipsilateral excitatory connections and not crossed inhibitory connections. This possible organization was supported by results from a computer model, which consisted of a pair of oscillators in the more rostral and more caudal spinal cord that could be connected by various types of coupling schemes. 5. The neurophysiological data above suggest that ipsilateral, excitatory coupling is stronger in the descending direction than in the ascending direction. In the computer model, a dominant descending coupling is a necessary requirement to produce positive longitudinal phase lags. Copyright © 1994 the American Physiological Society

Winslow, J. L.; Duffy, S. N.; Charlton, M. P.

doi: N/Apmid: 7823101

Abstract 1. Evoked neurotransmitter release at the crayfish neuromuscular junction was measured in the presence of the cell-permeant calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetotoxymethyl (BAPTA-AM). Excitatory post-synaptic potentials were greatly diminished after application of the intracellular chelator, an effect resulting from attenuation of the rise in the concentration of cytoplasmic Ca2+ (Cai) that is necessary for neurotransmission. However, short-term homosynaptic facilitation of release, the magnitude and time course of which is thought to depend on the accumulation and removal of residual Ca ions (Ca2+), was not affected. Application of the cell-permeant form of ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) gave similar results. 2. To interpret these results we developed a reaction-diffusion model in 3D rectangular coordinates for Ca2+ diffusion in the presence of mobile and immobile buffers. Solutions of the model in response to influx of Ca2+ through one or six channels for different diffusion coefficients and no nondiffusable buffer, predict that 1) the time course of residual Ca2+ is very brief, 2) an unrealistically low Ca2+ diffusion coefficient is required for residual calcium, 3) the spatially distributed Ca2+ signal is attenuated by intracellular BAPTA, 4) the rate at which free Ca2+ returns to resting levels, after entry (residual Ca2+) is faster with more mobile buffer, and 5) when pulse trains of Ca2+ channel current are used as input, computed facilitation is comparable to experimental measurements without buffer, but is abolished in the presence of exogenous buffer. 3. When the diffusion coefficient of Ca2+ in water is used, there is no residual Ca2+; however, when 0.1–1.6 mM nondiffusable buffer is present with a fast binding coefficient comparable to BAPTA, there is a very small residual Ca2+ due to the unbinding from the fixed binding sites. The nondiffusable buffer is saturated next to a Ca2+ channel. For this case of the diffusion coefficient of calcium in H2O and nondiffusable buffer, when a moderate amount of diffusable buffer is added to the system containing nondiffusable buffer, the very small residual Ca2+ is substantially reduced. This is because the product of diffusable buffer and Ca2+ is carried away as diffusable product, in contrast to the nondiffusable product releasing Ca2+, after Ca2+ entry ceases. 4. The model predicts that mobile calcium buffers with appropriate physical properties will attenuate facilitation and hasten its decay by removing residual calcium.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1994 the American Physiological Society

Lebedev, M. A.; Denton, J. M.; Nelson, R. J.

doi: N/Apmid: 7823093

Abstract 1. Primary somatosensory cortical (SI) neurons exhibit characteristic activity before the initiation of movements. This premovement activity (PMA) may result from centrally generated as well as from peripheral inputs. We examined PMA for 55 SI neurons (10, 13, 28, and 4 in areas 3a, 3b, 1, and 2, respectively) with activity that was entrained to vibrotactile stimulation (i.e., was temporally correlated with the stimulus). We sought to determine whether the temporal characteristics of vibration-entrained discharges would change throughout the reaction time period, and, if they did, whether these changes might be accounted for by central inputs. 2. Monkeys made wrist flexions and extensions in response to sinusoidal vibration (27, 57, or 127 Hz) of their palms. Vibration remained on until the animal moved at least 5 degrees from the initial hold position. Mean firing rate (MFR), a measure of the level of activity, was derived from the number of spikes per vibratory cycle. The correlation between the vibration and the neuronal firing was described by the mean phase (MP) of the vibratory cycle at which spikes occurred. The degree of entrainment was quantified as synchronicity (Synch), a statistical parameter that could change from 0 for no entrainment to 1 for responses at a constant phase. 3. Premovement MFR increases (activation) and decreases (suppression) were observed. Moreover, two changes in MFR often were observed for the same neuron (2-event PMA). Many MFR shifts, especially the first in the two-event PMA, preceded electromyographic (EMG) onset. The pre-EMG MFR shifts more often had the same sign both for flexion and extension movements rather than having opposite signs. However, with equal frequency, post-EMG PMA events had the same or opposite sign for different movement directions. We suggest that the pre-EMG PMA has an origin different from movement-related peripheral reafference. 4. Premovement activation was accompanied by shifts of MP corresponding to earlier responses to the ongoing vibratory stimulus and by decreases of response Synch. Premovement suppression was not associated with consistent shifts of MP and Synch. We suggest that during premovement activation, asynchronous (uncorrelated with vibration) signals are integrated with the vibratory input. These asynchronous signals may make neurons more likely to discharge and to do so earlier with respect to the vibratory stimulus. The asynchronous component may also disrupt the vibration-entrained activity pattern.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1994 the American Physiological Society

Simmons, M. L.; Terman, G. W.; Drake, C. T.; Chavkin, C.

doi: N/Apmid: 7823095

Abstract 1. Activation of kappa 1-opioid receptors inhibits excitatory transmission in the hippocampal dentate gyrus of the guinea pig. The present studies used both anatomic and physiological approaches to distinguish between a pre- and postsynaptic localization of these receptors. 2. The entorhinal cortex was lesioned unilaterally to cause degeneration of perforant path afferents to the dentate molecular layer, and kappa 1-opioid binding sites were measured by labeling with the selective agonist, 3H-U69593. Binding density was reduced significantly in the dentate gyrus molecular layer ipsilateral to the lesion compared with the contralateral molecular layer and with sham-lesioned controls. 3. Paired-pulse facilitation is a neurophysiologic paradigm that has been used to differentiate pre- and postsynaptic sites of action for agents that inhibit excitatory neurotransmission. U69593 reduced the amplitude of single population spikes and increased the degree of paired pulse facilitation. The potentiation of paired-pulse facilitation was maintained when the stimulation intensity was increased to compensate for the inhibition of excitatory transmission. These effects of kappa 1-receptor activation were similar to those seen after presynaptic inhibition of excitatory neurotransmitter release and support the hypothesis that U69593 presynaptically inhibits excitatory amino acid release in the dentate gyrus. 4. Local application of glutamate by pressure ejection in the dentate molecular layer evoked field excitatory postsynaptic potentials that mimicked those evoked by electrical stimulation of the perforant path. Both responses were sensitive to the non-N-methyl-D-aspartate glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. U69593 inhibited responses evoked by perforant path stimulation but had no effect on responses evoked by glutamate application.(ABSTRACT TRUNCATED AT 250 WORDS) Copyright © 1994 the American Physiological Society

Gottlieb, J. P.; MacAvoy, M. G.; Bruce, C. J.

doi: N/Apmid: 7823092

Abstract 1. Intracortical microstimulation of a portion of the monkey frontal eye field (FEF) lying in the floor and posterior bank of the arcuate sulcus evokes smooth, rather than saccadic eye movements. To further explore this region's involvement in pursuit, we recorded from FEF neurons in the vicinity of sites from which smooth eye movements (SEMs) were elicited electrically and studied their responses during smooth-pursuit and saccadic tasks. In this report, we describe the neurons' responses during visually guided smooth pursuit and compare their locations and response properties with those of elicited SEMs. 2. One hundred and ninety-three neurons, recorded from the FEF region in six hemispheres of three rhesus monkeys, were classified as “pursuit neurons”. These neurons responded during smooth-pursuit tracking of moving visual stimuli but had no, or only minimal, responses in conjunction with visually guided saccades. Pursuit neurons were located in a small region of the arcuate fundus and posterior bank that overlapped, and extended slightly beyond, the region from which SEMs were elicited with microstimulation. 3. All pursuit neurons had a preferred pursuit direction, and all directions were represented with no strong bias toward ipsilateral, contralateral, up, or down. The directional tuning of 80 pursuit cells was measured quantitatively by testing pursuit in several directions and fitting the responses to a Gaussian function. Tuning indices (the sigma parameter of the Gaussian fit) varied between 13 degrees and 136 degrees. The median tuning index, 44.5 degrees, corresponds to a full width at half maximum of 105 degrees. The ubiquity of selectivity for pursuit direction and the wide distribution of preferred directions indicates that pursuit direction uses a place-code type of representation in FEF; however, the broad directional tuning of most neurons suggests that pursuit direction is given by a weighted average of optimal directions across the population of pursuit neurons active at any given time. 4. In general, the responses of pursuit neurons increased with pursuit velocity. Of 13 neurons formally tested with 2 s of constant-velocity tracking in their preferred direction across a range of target speeds, pursuit velocity sensitivity ranged from 0.24 to 1.42 spikes.s-1.deg-1.s-1, with an average sensitivity of 0.70. This relationship suggests that pursuit neurons represent pursuit magnitude using a rate code; this parallels our previous observation that at most SEM sites, the velocity and acceleration of the electrically elicited eye movements increased as a function of the stimulation current.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1994 the American Physiological Society