bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity in the caudate nucleus of monkey during spatial sequencing
Authors: Kermadi I. , Joseph J. P.
Published: December 2017

1. There are indications that the execution of behavioral sequences involves the basal ganglia. In this study we examined the role of the caudate nucleus in the construction, storage, and execution of spatial plans. 2. Two monkeys (Macaca mulatta) were trained to perform sequences of saccades and arm movements. The animals had to remember the order of illumination, variable from one sequence to another, of three fixed spatial targets. After a delay, they had to visually orient toward, and press each target in the same order. Six different sequences were executed on the basis of the order of illumination of the targets. Single cell activity was recorded from the four caudate nuclei of the two monkeys. 3. Neural activity was analyzed in each sequence during 10 different periods: the instruction period in which the targets were illuminated, the three orientation periods toward the different targets, the three postsaccadic periods, and the three periods of target pressing. Statistical comparisons were made to detect differences between the different sequences with respect to activity in each period (sequence specificity). 4. A total of 2,100 neurons were studied, of which 387 were task related. The task-related cells were found in both the head and the body of the caudate nucleus. 5. During central fixation, anticipatory activity (n = 81) preceded onset of specific events. Four groups were considered: 1) neurons (n = 46) anticipating offset of the central fixation point, 2) neurons (n = 7) anticipating the illumination of any target, regardless of its spatial position or order of presentation (rank), 3) neurons (n = 17) anticipating the illumination of the first target, regardless of its spatial position, and 4) neurons (n = 11) anticipating the illumination of a given target, regardless of its rank. 6. Phasic visual responses to target onset were observed in 48 cells. The cells responded primarily to the contralateral and upper targets. In a majority (n = 35), visual responses were modulated by the rank of the target(s). Many cells (n = 20) responded only if the corresponding target was first; other cells responded only if the target was second or if it had complex time relationships with the other targets. 7. The responses of the cells to the same instruction stimuli repeated twice in a row, and under the condition that the animal did not behaviorally use the first instruction in between, were tested. More than one-third of the tested cells (n = 14) did not respond, or responded very weakly, to the second instruction.(ABSTRACT TRUNCATED AT 400 WORDS)
Restoration of extensor excitability in the acute spinal cat by the 5-HT2 agonist DOI
Authors: Miller J. F. , Paul K. D. , Lee R. H. , Rymer W. Z. , Heckman C. J.
Published: December 2017

1. The decerebrate cat preparation with an intact spinal cord is characterized by a high degree of excitability in extensor motoneuron pools, which is eliminated by acute spinalization. Subtype-specific agonists for serotonin (5-HT) were investigated in terms of their effectiveness in restoring the extensor excitability following spinalization. 2. Our hypothesis was that 5-HT2 receptors have the primary role in enhancement of extensor reflex excitability, whereas 5-HT1A and 5-HT1B/D receptors are relatively unimportant. Reflex excitability was assessed from the tonic levels of force and electromyographic (EMG) output from the ankle extensors medial gastrocnemius (MG) and soleus (SOL), and from the reflex forces in both these muscles generated by ramp-and-hold stretches of MG. 3. Before spinal transection, MG and SOL usually exhibited a small amount of tonic background EMG activity and force output. Ramp-and-hold stretch of MG generated a large-amplitude reflex response. Spinal transection at the level of T10 virtually abolished tonic background activity in both extensors and greatly attenuated the MG stretch reflex. Ventral topical application of the selective 5-HT2A/2C agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane hydrochloride (DOI) restored the amplitude of the MG stretch reflex in a dose-dependent fashion. However, a considerable portion of the DOI-mediated restoration of MG stretch reflex force was due to elevation of tonic background force levels above previous intact cord levels. 4. The DOI-induced increase in extensor tonic background excitability and facilitation of MG stretch reflex were reversed by ventral topical administration of the selective 5-HT2 antagonist ketanserin. No increase in extensor excitability was observed in spinalized preparations after administration of either the 5-HT1A agonist (+-)-8-hydroxy-dipropylaminotetralin hydrobromide or the 5-HT1B/1D agonist 7-trifluoromethyl-4-(4 methyl-1-piperazinyl)-pyrrolo[1,2- a]quinoxaline maleate. These data strongly suggest that the DOI-induced facilitation of extensor stretch reflex and tonic activity in spinalized preparations is mediated through an action on spinal 5-HT2 receptors. 5. One important difference between the actions of DOI in spinalized versus intact states was that the DOI-induced tonic and reflex forces in the spinalized state were subject to irregular oscillations. In contrast, DOI did not noticeably affect the smoothness of reflex force generation in the intact state. This discrepancy was probably due to the effects of clasp knife inhibition from muscular free nerve endings, which have potent reflex actions in the spinalized but not intact states. Thus DOI elevated excitability levels but did not alter the effects of spinalization on stretch reflex patterns.
Threshold serotonin concentration required to produce synaptic facilitation differs for depressed and nondepressed synapses in Aplysia sensory neurons
Authors: Emptage N. J. , Mauelshagen J. , Carew T. J.
Published: December 2017

1. The modulatory actions produced by the neurotransmitter serotonin (5HT) in Aplysia sensory neurons (SNs) can be distinguished on the basis of their concentration requirement for 5HT, their activation and recovery kinetics, and their dependence on the relative contribution of different second messenger pathways. In addition, some of the facilitatory mechanisms activated by 5HT appear to be different depending upon the recent activation history of synaptic transmission from the SNs. In this study, we examined the concentration requirements of 5HT-induced facilitation of depressed and nondepressed synapses. 2. In isolated pleural-pedal ganglia, we produced facilitation of monosynaptic connections between tail SNs and motor neurons (MNs), using different concentrations of 5HT. As a measure of each preparation's greatest sensitivity to 5HT, we first determined the lowest 5HT concentration that produced increased excitability in the SNs ("threshold" 5HT). Then, in one series of experiments, we applied 5HT sequentially to the same synapse, first in the nondepressed and then in the depressed state. In a second series, we applied 5HT simultaneously to two SNs connecting to the same MN; one synapse was depressed, the other nondepressed. 3. In both series of experiments, we found that the 5HT concentration required to produce facilitation of depressed excitatory post-synaptic potentials (EPSPs) was invariably lower than the 5HT concentration that produced facilitation of nondepressed EPSPs. In the first series, 'threshold' 5HT (1.6 microM) was sufficient to facilitate the synapse in the depressed state, but not the nondepressed state. However, the nondepressed synapse could still be facilitated by higher concentrations of 5HT (10 microM). In the second series, increased excitability of SNs, facilitation of depressed synapses, and facilitation of nondepressed synapses were progressively recruited as a function of increasing 5HT concentration (4.1, 6.7, and 10-15 microM, respectively). 4. These data are consistent with previous studies suggesting that different cellular mechanisms contribute to the facilitation of depressed and nondepressed synapses. In addition, our results provide a way to experimentally separate the two processes and to analyze them simultaneously and independently. Taking advantage of this dissociation, in future experiments it may be possible to directly compare the relative contributions of different intracellular mechanisms to synaptic facilitation and to relate them to the degree of recent synaptic activation.
Neural mechanisms of blood flow regulation during synaptic activity in cerebellar cortex
Authors: Iadecola C. , Li J. , Xu S. , Yang G.
Published: December 2017

1. We investigated the neural mechanisms of the increases in blood flow produced by synaptic activity using the parallel fiber (PF) system of the cerebellum as a model. The midline cerebellum was exposed in anesthetized rats and the PFs were stimulated with tungsten microelectrodes. Cerebellar blood flow (BFcrb) was recorded using a laser-Doppler probe, whereas field potentials were recorded using glass micropipettes. PF stimulation produced increases in BFcrb that were related to the frequency and intensity of stimulation (+60 +/- 9%, mean +/- SE, at 100 microA and 30 Hz; n = 6). The greatest increases were confined to a band stretching along the major axis of the stimulated folium and corresponding to the beam of activated PFs. The increase in evoked by PF stimulation was associated with a corresponding increase in glucose utilization, assessed by the 2-deoxyglucose method. The increases in BFcrb and the field potentials evoked by PF stimulation were abolished by tetrodotoxin (1 microM; n = 6). Ringer solution containing 12 mM Mg2+ and 0 mM Ca2+ blocked synaptic activity in the PFs and abolished the increases in flow (P > 0.05 from baseline; n = 5). The broad-spectrum glutamate receptor antagonist kynurenate (5 mM) prevented depolarization of Purkinje cells and interneurons and abolished the increase in BFcrb evoked by PF stimulation (P > 0.05; n = 6). Treatment with tetrodotoxin, Mg2+, or kynurenate did not affect the increase in BFcrb elicited by systemic hypercapnia or by topical application of the nitric oxide donor 3-morpholino sydnonimine (P > 0.05 from Ringer solution). We conclude that the increases in flow produced by synaptic activity are linked to glutamate-induced depolarization of Purkinje cells and interneurons. These findings provide evidence that activation of glutamate receptors participates in the mechanisms of functional hyperemia, and they support the validity of the PF system as a model for study of the relationship between synaptic activity and blood flow in the CNS.
Two types of network oscillations in neocortex mediated by distinct glutamate receptor subtypes and neuronal populations
Authors: Flint A. C. , Connors B. W.
Published: December 2017

1. Two distinct forms of spontaneous synchronous oscillations were investigated with field potential recordings in slices of rat somatosensory cortex in vitro. 2. The first type of synchronous oscillation was activated by low extracellular [Mg2+] and had dominant frequencies of 8-12 Hz. It was abolished reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphonovaleric acid and was relatively unaffected by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). The duration of oscillatory events was increased by blocking gamma-aminobuturic acid-A receptors with bicuculline or by activating metabotropic glutamate receptors with trans-1-aminocyclopentane-1,3-dicarboxylic acid. 3. A second form of synchronous oscillation was activated by acute application of kainic acid (10 microM), had dominant frequencies of 1-5 Hz, and was abolished reversibly by DNQX. Low concentrations of domoic acid mimicked the effects of kainate, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or quisqualic acid did not, suggesting a role for the GluR5-7 and KA1-2 glutamate receptor subunits. 4. Surgical isolation of cortical layers showed that spontaneous NMDA receptor-dependent oscillations originated within layer 5 exclusively, but kainate receptor-dependent oscillations were uniquely generated by neurons in layers 2/3. 5. Our results suggest that neocortical neurons in layers 2/3 and layer 5 can independently generate two distinct forms of rhythmic population activity, each dependent upon activation of a different subtype of glutamate receptor.
Spatial properties of envelope-responsive cells in area 17 and 18 neurons of the cat
Authors: Zhou Y. X. , Baker C. L.
Published: December 2017

1. Many neurons in areas 17 and 18 respond to spatial contrast envelope stimuli whose Fourier components fall outside the cell's spatial-frequency-selective range. The spatial properties of such envelope responses are investigated here and compared with responses to conventional luminance-defined gratings to explore the underlying receptive-field mechanism. 2. Three spatial properties of envelope responses are reported more extensively in this paper. First, the envelope responses were selective to the carrier spatial frequency in a narrow range of frequencies higher than a given cell's luminance spatial frequency selective range (luminance passband). Second, a given cell's dependence on envelope spatial frequency often differed from its luminance passband. Last, the optimal carrier spatial frequency did not shift systematically with the envelope spatial frequency, supporting the hypothesis that the carrier and envelope spatial-frequency dependencies were mediated by distinct mechanisms. 3. In contrast to the direction selectivity to the envelope motion in many envelope-responsive cells, no direction preference to carrier motion was found for envelope responses. The direction of carrier motion did not alter the direction selectivity for envelope motion, further supporting the hypothesis that the carrier and envelope temporal properties were mediated by separate mechanisms. 4. The distributions of the optimal carrier and luminance spatial frequencies among envelope-responsive cells were analyzed. The optimal carrier spatial frequencies were randomly distributed from five times the cell's optimal luminance spatial frequency to the upper resolution limit of the X-retinal ganglion cells at the same retinal eccentricity, suggesting that the selective ranges of envelope responses and luminance responses are not strongly correlated over the population of envelope-responsive cells. 5. Our data support a "two-stream" receptive-field model for envelope-responsive cells. One stream is a conventional, spatially linear receptive-field mechanism, mediating luminance responses for the cell; the other mediates envelope responses and consists of a two-stage processing: a set of spatially small and distributed nonlinear neural subunits whose outputs are spatially pooled at the second stage. 6. In conclusion, this study indicates that envelope responses in area 17 and 18 neurons cannot be due to a nonlinearity that is common to all visual stimuli before narrowband spatial-frequency-selective filtering; instead, a specialized processing stream, parallel to the conventional luminance response stream, is needed to supplement the traditional luminance processing stream in these cells. This specialized stream responds to the envelope stimuli and is selective to their carrier and envelope spatial frequencies. The distributions of the optimal luminance and carrier spatial frequencies indicate a rich variety of possible integration between luminance and envelope information.
Contribution of hind limb flexor muscle afferents to the timing of phase transitions in the cat step cycle
Authors: Hiebert G. W. , Whelan P. J. , Prochazka A. , Pearson K. G.
Published: December 2017

1. In this investigation, we tested the hypothesis that muscle spindle afferents signaling the length of hind-leg flexor muscles are involved in terminating extensor activity and initiating flexion during walking. The hip flexor muscle iliopsoas (IP) and the ankle flexors tibialis anterior (TA) and extensor digitorum longus (EDL) were stretched or vibrated at various phases of the step cycle in spontaneously walking decerebrate cats. Changes in electromyogram amplitude, duration, and timing were then examined. The effects of electrically stimulating group I and II afferents in the nerves to TA and EDL also were examined. 2. Stretch of the individual flexor muscles (IP, TA, or EDL) during the stance phase reduced the duration of extensor activity and promoted the onset of flexor burst activity. The contralateral step cycle also was affected by the stretch, the duration of flexor activity being shortened and extensor activity occurring earlier. Therefore, stretch of the flexor muscles during the stance phase reset the locomotor rhythm to flexion ipsilaterally and extension contralaterally. 3. Results of electrically stimulating the afferents from the TA and EDL muscles suggested that different groups of afferents were responsible for the resetting of the step cycle. Stimulation of the TA nerve reset the locomotor step cycle when the stimulus intensity was in the group II range (2-5 xT). By contrast, stimulation of the EDL nerve generated strong resetting of the step cycle in the range of 1.2-1.4 xT, where primarily the group Ia afferents from the muscle spindles would be activated. 4. Vibration of IP or EDL during stance reduced the duration of the extensor activity by similar amounts to that produced by muscle stretch or by electrical stimulation of EDL at group Ia strengths. This suggests that the group Ia afferents from IP and EDL are capable of resetting the locomotor pattern generator. Vibration of TA did not affect the locomotor rhythm. 5. Stretch of IP or electrical stimulation of TA afferents (5 xT) during the flexion phase did not change the duration of the flexor activity. Stimulation of the EDL nerve at 1.8-5 xT during flexion increased the duration of the flexor activity. In none of our preparations did we observe resetting to extension when the flexor afferents were activated during flexion. 6. We conclude that as the flexor muscles lengthen during the stance phase of gait, their spindle afferents (group Ia afferents for EDL and IP, group II afferents for TA) act to inhibit the spinal center generating extensor activity thus facilitating the initiation of swing.
Additivity of loud-sound--induced threshold losses in the cat under conditions of active or inactive cochlear efferent-mediated protection
Authors: Rajan R.
Published: December 2017

1. An additivity model for the accretion of cochlear sensorineural hearing losses has been described from studies in the guinea pig cochlea. Among other aspects, the model allows determination of how residual hearing losses after an initial exposure (E1) affect hearing losses to be expected to a subsequent second exposure (E2). In the present study, the model was applied to temporary hearing losses produced in the cat cochlea by loud pure tones at a frequency from 3 to 15 kHz, affecting regions from 2 to 28 kHz. Successive identical exposures, generally with an interexposure interval of approximately equal to 35 min, were used to produce compound action potential (CAP) threshold losses. Total losses after E2 were compared with those predicted by the model. Testing was carried out under conditions where olivocochlear bundle (OCB)-mediated protection was or was not activated. (As shown elsewhere, OCB-mediated protection is activated by particular binaural exposures, but not monaural exposure, and reduces threshold losses in the binaural condition with intact OCB compared with losses in either the monaural condition, or the binaural condition where the OCB was cut before loud sound.) 2. The additivity model was a very good predictor of total losses under a variety of conditions; different exposure frequencies, monaural and binaural exposures, and with intact or cut OCB pathways. In these exposures, the model's application could be generalized so that as long as residual losses just pre-E2 were well specified in an animal, total losses could be as well predicted using normative data bases of a single exposure with the same parameters. 3. The model also allowed determination of whether OCB-mediated protection was exercised during E2 in dual identical exposures. Expression of protection for E2 depended on whether E1 elicited protection. When tested with monaural (at 7 or 15 kHz) or binaural exposures (at kHz) for which E1 did not elicit protection, neither did E2. However, when tested with a binaural E1 (at 7, 11, or 15 kHz), which activated protection, E2 also elicited protection. In the latter case, for 7- and 11-kHz exposures, the amount of E2 protection increased with total hearing loss, a relationship similar to that seen for single exposures in cat and guinea pig. For 15-kHz exposure, the amount of E2 protection was constant across test frequencies. 4. Finally, a critical observation with 11-kHz exposure was that a binaural E1 eliciting protection was able to "prime" the OCB so that protection could be elicited by a subsequent monaural E2, which, by itself as a singel exposure, does not evoke protection. This result has important implications in terms of the physiology of the protective OCB pathways and clinically in terms of the manner in which loud-sound-induced hearing loss accumulated.
Oscillatory firing and interneuronal correlations in squirrel monkey striate cortex
Authors: Livingstone M. S.
Published: December 2017

1. This work explores a mechanism that the brain may use for linking related percepts. It has been proposed that temporal relationships in the firing of neurons may be important in indicating how the stimuli that activate those neurons are related in the external world. Such temporal relationships cannot be seen with conventional receptive field mapping but require cross-correlation and auto-correlation analysis. 2. In the cat and the macaque monkey, cells with similar receptive field properties show correlated firing even when their receptive fields do not overlap. Here I report that in the squirrel monkey, as in the cat, pairs of cells < or = 5 mm apart can show correlated firing, and these correlations between pairs of cells are often stronger when they are stimulated by a single contour. This suggests that the correlations reflect not only permanent connections between cells with similar receptive fields, but in addition may encode information that the activating stimuli are continuous or part of a single object. I also find that, as in the cat, and contrary to some other reports on experiments in monkeys, the correlated firing is often rhythmic. These recordings further indicate that periods of rhythmicity are associated with stronger interneuronal synchrony, which is consistent with the hypothesis that recurrent feedback loops are involved in generating both. 3. Pairs of cells in the same cortical column, but at different depths also showed correlated firing, but with several milliseconds difference in timing between layers. This was true for cells at different depths within layer 2/3 and for pairs of cells in different layers (2/3 vs. 4B or 4C alpha), providing evidence for cross-talk between the magno- and parvocellular streams.
Swelling-activated amino acid efflux in the human neuroblastoma cell line CHP-100
Authors: Basavappa S. , Huang C. C. , Mangel A. W. , Lebedev D. V. , Knauf P. A. , Ellory J. C.
Published: December 2017

1. The effects of hypoosmotic stress on cell volume and amino acid efflux were evaluated in the human neuroblastoma cell line CHP-100 with the Coulter Counter Multisizer and radiolabeled amino acid efflux, respectively. 2. CHP-100 cells swelled by approximately 35 +/- 5% (means +/- SE) when the osmolarity of the solution was decreased from 290 to 190 mOsm/kg H2O. The rapid swelling was followed by a biphasic regulatory volume decrease (RVD). 3. In cells loaded with 14C-taurine, hypoosmotic stress induced a 300 +/- 22% (n = 23, P < 0.05) increase in taurine efflux compared with controls. This efflux was inhibited by the chloride channel blockers 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS), niflumic acid and by the volume-activated anion channel blocker tamoxifen. In addition, the swelling-activated taurine efflux was dependent upon extracellular calcium. 4. Similarly, in cells loaded with 14C-glycine, hypoosmotic stress significantly increased glycine efflux, which was also sensitive to NPPB. In contrast, efflux of 3H-glutamate was not significantly altered after hypoosmotic stress. 5. With the use of patch clamp recording techniques, Cl- channels were activated in cell attached patches after exposure to hypoosmotic solutions. 6. In nystatin perforated patches, permeability of the hypoosmotically activated anion channel was observed to be SCN- > I- > Br- > Cl- >> Glutamate. 7. It is concluded that in CHP-100 cells, anion channels are activated during hypoosmotic stress and these channels represent a pathway for efflux of amino acids.
MicroO-conotoxin MrVIA inhibits mammalian sodium channels, but not through site I
Authors: Terlau H. , Stocker M. , Shon K. J. , McIntosh J. M. , Olivera B. M.
Published: December 2017

1. A 31-amino-acid peptide from the venom of the snail-hunting species Conus marmoreus, microO-conotoxin MrVIA, inhibits mammalian voltage-gated sodium channels through a novel mechanism distinct from saxitoxin, tetrodotoxin, or mu-conotoxin. 2. MicroO-Conotoxin MrVIA blocks rat brain type II sodium channels expressed in Xenopus oocytes (IC50 approximately 200 nM, Hill coefficient approximately 1.6 +/- 0.2, mean +/- SE). Channel activation/inactivation kinetics and current-voltage relationships were unperturbed. 3. MicroO-Conotoxin MrVIA does not cause phasic or use-dependent inhibition of sodium currents measured in Xenopus oocytes expressing rat brain type II sodium channels, but shifts the steady-state availability of these sodium channels to more hyperpolarized potentials. 4. MicroO-Conotoxin MrVIA inhibited rapidly inactivating sodium channel conductance in rat hippocampal cells in culture. The inhibition was rapidly reversible. 5. MicroO-Conotoxin MrVIA does not displace specific [3H]saxitoxin binding to either rat brain or Electrophorus electric organ sites, indicating inhibitory effects mediated through a binding site distinct from site I.
Amplitude and time course of spontaneous and evoked excitatory postsynaptic currents in bushy cells of the anteroventral cochlear nucleus
Authors: Isaacson J. S. , Walmsley B.
Published: December 2017

1. Spontaneous and evoked excitatory postsynaptic currents (EPSCs) were recorded in slices of the rat anteroventral cochlear nucleus (AVCN) at the endbulb-bushy cell synaptic connection. 2. The amplitudes of alpha-amino-3-hydroxy-5-methy-4-isoxa-zolepropionic acid (AMPA)-receptor-mediated spontaneous EPSCs were large (54 +/- 6 pA, mean +/- SD; membrane potential = -70 mV, 22-25 degrees C) and, in the same cell, exhibited a very wide range of peak amplitudes (CM = 0.42 +/- 0.01, n - 15 cells). There was no significant correlation between rise times or decay time constants and the peak amplitudes of spontaneous EPSCs recorded in the same cell, demonstrating that electrotonic attenuation is not responsible for the large amplitude variability of spontaneous EPSCs. 3. Cyclothiazide, a potent blocker of AMPA-receptor desensitization, did not affect the amplitude of spontaneous EPSCs in AVCN bushy cells, suggesting that background desensitization of AMPA receptors is not significant in these cells. However, the decay time constant of spontaneous EPSCs was prolonged significantly (2.6-fold increase). In addition, cyclothiazide produced a marked increase (approximately 40%, n = 6 cells) in the frequency of spontaneous EPSCs, indicating a likely presynaptic site of action of this drug. 4. Cyclothiazide produced a small increase (approximately 10%, n = 7 cells) in the peak amplitude of the evoked endbulb EPSC, but this effect could be explained by the action of cyclothiazide to increase the decay time constant of the underlying quantal EPSCs in conjunction with the asynchrony of quantal transmitter release at the endbulb synapse. 5. These results indicate that neither electrotonic attenuation nor receptor desensitization are responsible for the wide range of peak amplitudes of spontaneous EPSCs in bushy cells. The large quantal variability therefore is likely to be due entirely to intrinsic fluctuations at each release site and site-to-site variability in the numbers of available receptors.
Neural correlates of the pitch of complex tones. I. Pitch and pitch salience
Authors: Cariani P. A. , Delgutte B.
Published: December 2017

1. The temporal discharge patterns of auditory nerve fibers in Dial-anesthetized cats were studied in response to periodic complex acoustic waveforms that evoke pitches at their fundamental frequencies. Single-formant vowels, amplitude-modulated (AM) and quasi-frequency-modulated tones. AM noise, click trains, and other complex tones were utilized. Distributions of intervals between successive spikes ("1st-order intervals") and between both successive and nonsuccessive spikes ("all-order intervals") were computed from spike trains. Intervals from many fibers were pooled to estimate interspike interval distributions for the entire auditory nerve. Properties of these "pooled interspike interval distributions," such as the positions of interval peaks and their relative heights, were examined for correspondence to the psychophysical data on pitch frequency and pitch salience. 2. For a diverse set of complex stimuli and levels, the most frequent all-order interspike interval present in the pooled distribution corresponded to the pitch heard in psychophysical experiments. Pitch estimates based on pooled interval distributions (30-85 fibers, 100 stimulus presentations per fiber) were highly accurate (within 1%) for harmonic stimuli that produce strong pitches at 60 dB SPL. 3. Although the most frequent intervals in pooled all-order interval distributions were very stable with respect to sound intensity level (40, 60, and 80 dB total SPL), this was not necessarily the case for first-order interval distributions. Because the low pitches of complex tones are largely invariant with respect to level, pitches estimated from all-order interval distributions correspond better to perception. 4. Spectrally diverse stimuli that evoke similar low pitches produce pooled interval distributions with similar most-frequent intervals. This suggests that the pitch equivalence of these different stimuli could result from central auditory processing mechanisms that analyze interspike interval patterns. 5. Complex stimuli that evoke strong or "salient" pitches produce pooled interval distributions with high peak-to-mean ratios. Those stimuli that evoke weak pitches produce pooled interval distributions with low peak-to-mean ratios. 6. Pooled interspike interval distributions for stimuli consisting of low-frequency components generally resembled the short-time auto-correlation function of stimulus waveforms. Pooled interval distributions for stimuli consisting of high-frequency components resembled the short-time autocorrelation function of the waveform envelope. 7. Interval distributions in populations of neurons constitute a general, distributed means of encoding, transmitting, and representing information. Existence of a central processor capable of analyzing these interval patterns could provide a unified explanation for many different aspects of pitch perception.
Serotonin potentiates dopamine inhibition of ventral tegmental area neurons in vitro
Authors: Brodie M. S. , Bunney E. B.
Published: December 2017

1. The ventral tegmental area (VTA) has been implicated in both the rewarding effects of drugs of abuse and the etiology of schizophrenia. We report here that serotonin (5-HT) potentiates the inhibitory effect of dopamine on dopaminergic VTA neurons. Dopamine (0.5-10 microM) inhibited the spontaneous firing of putative dopamine-containing neurons of the VTA. 5-HT (5-10 microM) itself did not significantly alter the spontaneous firing rate; however, in the presence of 5-HT, the inhibitory potency of dopamine was significantly increased. 2. The inhibitory potency of the dopamine agonist quinpirole was also increased by 5-HT. 3. 5-HT-induced potentiation was also produced by the selective 5-HT2 agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine, and was reversed by the selective 5-HT2 antagonist ketanserin. 4. This novel action of 5-HT on dopaminergic neurons has important implications for the development of drugs to treat schizophrenia, and for the identification of agents that will be useful in treating drug abuse disorders like alcoholism.
Kinetics of slow inactivation of persistent sodium current in layer V neurons of mouse neocortical slices
Authors: Fleidervish I. A. , Gutnick M. J.
Published: December 2017

1. In whole cell recordings from layer V neurons in slices of mouse somatosensory neocortex, tetrodotoxin (TTX)-sensitive persistent Na+ current (INaP) was studied by blocking K+ currents with intracellular Cs+ and Ca2+ currents with extracellular Cd2+. During slow voltage ramps, INaP began to activate at around -60 mV, and attained a peak at around -25 mV. The peak amplitude of INaP varied widely from cell to cell (range 60-3,160 pA; median 308 pA, n = 77). At potentials more positive than -35 mV, INaP in all cells was superimposed on a large, TTX-resistant outward current. 2. In hybrid clamp experiments, INaP was significantly reduced by a preceding high-frequency train of spikes. 3. INaP underwent pronounced slow inactivation, which was revealed by systematically varying the ramp speed between 233 and 2.33 mV/s, or varying the duration of a depolarizing prepulse between 0.1 and 10 s. 4. Onset of slow inactivation at +20 mV was monoexponential with tau = 2.06 s (n = 17 cells). Recovery from slow inactivation was voltage dependent. It followed a monoexponential time course with tau = 2.31 s (n = 6) at -70 mV and tau = 1.10 s (n = 4) at -90 mV. These values are not significantly different than values previously reported for slow inactivation of fast-inactivating INa. 5. Slow inactivation of neocortical INaP will influence all neuronal functions in which this current plays a role, including spike threshold determination, synaptic integration, and active propagation in dendrites. The kinetics of slow inactivation suggest that it may be a factor not only during extremely intense spiking, but also during periods of "spontaneous" activity.
Modulation of calcium currents by electrical activity
Authors: Li M. , Jia M. , Fields R. D. , Nelson P. G.
Published: December 2017

Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures for 1-2 days produced a downregulation of voltage sensitive calcium currents, which persisted for > or = 24 h after stimulation was terminated. This regulation varied with different patterns of activation. Both the magnitude and time course of regulation of the low-threshold voltage-activated (LVA) and high-threshold voltage-activated (HVA) currents were differentially sensitive to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation (10 Hz for 0.5 s every 2 s) with an average frequency of 2.5 Hz produced significantly more downregulation of HVA currents than did the tonic 2.5-Hz stimulation. The efficacy of phasic stimulation varied inversely with the interval between bursts. Thus phasic stimulation of 10 Hz for 0.5 s but delivered every 4 s produced no effects on HVA currents. Stimulation optimal for downregulation of Ca2+ currents also produced a decreased binding by the DRG neurons of an L-type Ca2+ channel antagonist. This suggests a downregulation by electrical activity of the number of Ca2+ channels, rather than an alteration in a constant number of channels. Depression of LVA currents was produced by all stimulus patterns tested, including 0.5-Hz tonic stimulation. Chronic stimulation with a stimulation pattern that downregulated Ca2+ currents also produced a slowing of the increase in intracellular Ca2+ (as measured by Fura-2/AM) that is produced acutely by repetitive stimulation. This is consonant with earlier studies of intracellular Ca2+ concentration kinetics in growth cones.
Age-related impaired reflex sensitivity in a human hand muscle
Authors: Corden D. M. , Lippold O. C.
Published: December 2017

1. The rectified and averaged electromyogram (EMG) was recorded from the first dorsal interosseous muscle (FDI) in normal male and female human subjects, ranging in age from 18 to 67 yr. It was elicited by a brief stretch, given to the outstretched forefinger. 2. The responses to stretch consisted of components W30, the monosynaptic stretch reflex and W60, which is likely to arise in the skin and nonmuscular structures. The figures 30 and 60 refer to the mean latencies, in milliseconds, of the respective waveforms (W). 3. For a group of subjects > 30 yr of age, W30 was significantly smaller than in a group under this age. The size of W60 was not related to age and the W30/W60 ratio was < 0.45 in the older subjects. In the younger group, the ratio was always above 0.5. 4. The fact that the age-related reflex impairment affects only W30 and not W60, indicates that central processing in the motor neuron pool is unlikely to be the mechanism involved in the impairment. 5. Control experiments show that changes in frictional resistance in muscles, joints, and tendons with age, are not large enough to account for these results. 6. Neuromuscular block did not occur in these experiments and could not be implicated in the impaired reflex sensitivity.
Analysis of dynamic spectra in ferret primary auditory cortex. II. Prediction of unit responses to arbitrary dynamic spectra
Authors: Kowalski N. , Depireux D. A. , Shamma S. A.
Published: December 2017

1. Responses of single units and multiunit clusters were recorded in the ferret primary auditory cortex (AI) with the use of broadband complex dynamic spectra. Previous work has demonstrated that simpler spectra consisting of single moving ripples (i.e., sinusoidally modulated spectral profiles that travel at a constant velocity along the logarithmic frequency axis) could be used effectively to characterize the response fields and transfer functions of AI cells. 2. A complex dynamic spectral profile can be thought of as being the sum of moving ripple spectra. Such a decomposition can be computed from a two-dimensional spectrotemporal Fourier transform of the dynamic spectral profile with moving ripples as the basis function. 3. Therefore, if AI units were essentially linear, satisfying the superposition principle, then their responses to arbitrary dynamic spectra could be predicted from the responses to single moving ripples, i.e., from the units' response fields and transfer functions (spectral and temporal impulse response functions, respectively). 4. This conjecture was tested and confirmed with data from 293 combinations of moving ripples, involving complex spectra composed of up to 15 moving ripples of different ripple frequencies and velocities. For each case, response predictions based on the unit transfer functions were compared with measured responses. The correlation between predicted and measured responses was found to be consistently high (84% with rho > 0.6). 5. The distribution of response parameters suggests that AI cells may encode the profile of a dynamic spectrum by performing a multiscale spectrotemporal decomposition of the dynamic spectral profile in a largely linear manner.
Discharge of superior collicular neurons during saccades made to moving targets
Authors: Keller E. L. , Gandhi N. J. , Weir P. T.
Published: December 2017

1. The discharge of neurons in the deeper layers of the monkey superior colliculus was recorded during saccades made to stationary and to smoothly moving visual targets. 2. All neurons that discharged for saccades made to stationary targets also discharged during saccades made to moving targets, but there was a systematic shift in the saccade vector yielding maximal activity (i.e. center of the movement field) of collicular neurons for the latter class of movements. The shift moved the center of the movement fields toward larger-amplitude pursuit saccades for target motion away from the fovea, in comparison with saccades made to stationary targets. However, the discharge at the center of the movement field for pursuit saccades was 14% lower when averaged over the sample of recorded cells. 3. The saccades made during pursuit tracking of moving visual stimuli have different dynamics than saccades made to stationary targets. At similar amplitudes pursuit saccades are slower, and their velocity profiles often show secondary velocity peaks or inflection points and have longer-duration decelerating phases. 4. The combined experimental observations of a change in saccade dynamics and the shift in movement fields in collicular neurons for pursuit saccades are compatible with the hypothesis that saccades made to moving targets are controlled by neural processing in two partially separate pathways. In this theory, one path is concerned with correction of a presaccadic retinal position error (a path that includes the colliculus) and another path is concerned with position extrapolations based on the velocity of the moving target (a path that does not include the colliculus).
Locomotor Rhythm Evoked by Ventrolateral Funiculus Stimulation in the Neonatal Rat Spinal Cord In Vitro
Authors: Magnuson David S. K. , Trinder Tammy C.
Published: December 2017

Magnuson, David S. K. and Tammy C. Trinder. Locomotor rhythm evoked by ventrolateral funiculus stimulation in the neonatal rat spinal cord in vitro. J. Neurophysiol. 77: 200–206, 1997. Spinal cords from 2- to 8-day-old rats, maintained in vitro, were used to investigate the effects of discrete electrical stimuli applied to the ventrolateral funiculus (VLF) on motor neuron activity recorded from the lumbar ventral roots. Short trains of stimuli (1–3 s) delivered to one VLF in the low cervical region elicited rhythmic activity that persisted for up to 30 s. Responses consisted of short periods of activity (1–5 s) occurring simultaneously in the ipsilateral L5 and contralateral L3 ventral roots that alternated with similar bursts of activity in the ipsilateral L3 ventral root, a pattern consistent with locomotion. The rhythmicity of the ventral root responses to VLF stimulation was not affected by midsagittal sectioning of the preparation rostral to T10 and/or caudal to L4. Midsagittal sectioning of the lower thoracic or upper lumbar segments, however, disrupted the rhythmicity of the ventral root responses, leaving only long-duration simultaneous activation of the ipsilateral roots following VLF stimulus trains. The minimum lesion that effectively abolished the rhythmicity was one that divided only the L2 and L3 segments. In preparations rendered arrhythmic to VLF stimulation by an L2/L3 midsagittal lesion, rhythmicity could still be induced by N-methyl-d-aspartate (NMDA; 2–5 μM) and serotonin (5-HT; 20–50 μM), a drug combination commonly used to induce locomotor-like rhythmicity and air-stepping in vitro. Field potentials recorded following single stimuli delivered to the VLF revealed short-latency, large-amplitude responses in the ventral horn and intermediate gray both ipsilateral and contralateral to the stimulus site at T12 and L2. These observations suggest that 1) the discrete pathway under study may be an important descending locomotor command pathway and 2) this pathway has a strong bilateral projection in the lower thoracic and upper lumbar segments that is crucial for the initiation of VLF-induced rhythmic motor output. The induction of rhythmicity by NMDA/5-HT in an L2/L3-lesioned preparation suggests that these two rhythmogenic mechanisms may represent different levels within the circuitry that comprises the central pattern generator for locomotion. The rhythmic activity resulting from VLF stimulation is dependent on a bilateral projection that can be bypassed by the generalized excitation and subsequent rhythmicity that results from bath application of the NMDA/5-HT combination.
Thalamic Relay of Afferent Responses to 1- to 12-Hz Whisker Stimulation in the Rat
Authors: Hartings Jed A. , Simons Daniel J.
Published: December 2017

Hartings, Jed A. and Daniel J. Simons. Thalamic relay of afferent responses to 1- to 12-Hz whisker stimulation in the rat. J. Neurophysiol. 80: 1016–1019, 1998. Somatosensory cortical neurons in the rat can be entrained to frequencies of pulsatile whisker stimulation up to at least 12 Hz. A recent study proposed that such entrainment depends on oscillatory corticothalamic feedback. According to this model, thalamic relay neurons function as comparators of ascending and descending signals and should vary their response magnitudes and latencies as a function of peripheral stimulation frequency. Here we report, however, that the responses of thalamic relay neurons to 1- to 12-Hz pulsatile whisker deflections are constant in magnitude and latency over these frequencies. In addition, their cycle-by-cycle responses are as invariant as those of primary afferent neurons. These results support the view that thalamic relay neurons are driven primarily by ascending afferent signals and thereby entrain cortical neurons to peripheral stimulation by means of a direct feed-forward mechanism.
Myelinated Mechanically Insensitive Afferents From Monkey Hairy Skin: Heat-Response Properties
Authors: Treede Rolf-Detlef , Meyer Richard A. , Campbell James N.
Published: December 2017

Treede, Rolf-Detlef, Richard A. Meyer, and James N. Campbell. Myelinated mechanically insensitive afferents from monkey hairy skin: heat-response properties. J. Neurophysiol. 80: 1082–1093, 1998. To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 Aβ-fibers, 79 Aδ-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors ( n = 91) or low-threshold cold receptors ( n = 11). Nine Aβ-fibers and 41 Aδ-fibers were cutaneous nociceptors, and four Aδ-fibers innervated subcutaneous tissue. The majority of cutaneous A-fiber nociceptors were heat sensitive (43/50 = 86%). Heat-insensitive cutaneous A-fiber nociceptors consisted of one cold nociceptor, three silent nociceptors, and three high-threshold mechanoreceptors. Two types of response were observed to an intense heat stimulus (53°C, 30 s). Type I ( n = 26) was characterized by a long latency (mean: 5 s) and a late peak discharge (16 s). Type II ( n = 17) was characterized by a short latency (0.2 s) and an early peak discharge (0.5 s). Type I fibers exhibited faster conduction velocities (25 vs. 14 m/s) and higher heat thresholds (>53 vs. 47°C, 1-s duration) than type II fibers. The possibility that the type I heat response was a result of sensitization was tested in three fibers by determining the heat threshold to 30-s duration stimuli (42–46°C). For this long stimulus duration heat thresholds were reproducible across multiple runs, and the threshold to the 1-s duration stimulus was not altered by these tests. Thus fibers with a type I heat response were not high-threshold mechanoreceptors that developed a heat response through sensitization. Fibers with a type II heat response had significantly higher mechanical thresholds (median: 15 bar) than fibers with a type I heat response (5 bar). This finding accounts for the observation that type II heat responses were infrequently observed in earlier studies wherein the search technique depended on mechanical responsiveness. Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.