bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Role of GABAAReceptor–Mediated Synaptic Potentials During Swimming in PostembryonicXenopus laevisTadpoles
Authors: Reith Carolyn A. , Sillar Keith T.
Published: December 2017

We have investigated the contribution of GABAAreceptor activation to swimming in Xenopus tadpoles during the first day of postembryonic development. Around the time of hatching stage (37/8), bicuculline (10–50 μM) causes a decrease in swim episode duration and cycle period, suggesting that GABAAreceptor activation influences embryonic swimming. Twenty-four hours later, at stage 42, GABAAreceptor activation plays a more pronounced role in modulating larval swimming activity. Bicuculline causes short, intense swim episodes with increased burst durations and decreased cycle periods and rostrocaudal delays. Conversely, the allosteric agonist, 5β-pregnan-3α-ol-20-one (1–10 μM) or the uptake inhibitor, nipecotic acid (200 μM) cause slow swimming with reduced burst durations and increased cycle periods. These effects appear to be mainly the result of GABA release from the spinal terminals of midhindbrain reticulospinal neurons but may also involve spinal GABAergic neurons. Intracellular recordings were made using KCl electrodes to reverse the sign and enhance the amplitude of chloride-dependent inhibitory postsynaptic potentials (IPSPs). Recordings from larval motoneurons in the presence of strychnine (1–5 μM), to block glycinergic IPSPs, provided no evidence for any GABAergic component to midcycle inhibition. GABA potentials were observed during episodes, but they were not phase-locked to the swimming rhythm. Bicuculline (10–50 μM) abolished these sporadic potentials and caused an apparent decrease in the level of tonic depolarization during swimming activity and an increase in spike height. Finally, in most larval preparations, GABA potentials were observed at the termination of swimming. In combination with the other evidence, our data suggest that midhindbrain reticulospinal neurons become involved in an intrinsic pathway that can prematurely terminate swim episodes. Thus during the first day of larval development, endogenous activation of GABAAreceptors plays an increasingly important role in modulating locomotion, and GABAergic neurons become involved in an intrinsic descending pathway for terminating swim episodes.
Spinal Laminae I-II Neurons in Rat Recorded In Vivo in Whole Cell, Tight Seal Configuration: Properties and Opioid Responses
Authors: Light Alan R. , Willcockson Helen H.
Published: December 2017

Using the in vivo whole cell recording procedure described previously, we recorded 73 neurons in laminae I and II in the lumbar spinal cord of the rat. Input impedances averaged 332 MΩ, which indicated that prior sharp electrode recordings contained a significant current shunt. Characterization of the adequate stimuli from the excitatory hindlimb receptive field indicated that 39 of 73 neurons were nociceptive, 6 were innocuous cooling cells, 20 responded maximally to brush, and 8 cells were not excited by stimulation of the skin of the hindlimb. The locations of 15 neurons were marked with biocytin. Nociceptive neurons were mostly found in lamina I and outer II, cooling cells in lamina I, and innocuous mechanoreceptive cells were mostly found in inner II or in the overlying white matter. The μ-opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) hyperpolarized 7 of 19 tested neurons with a conductance increase. This hyperpolarization was reversed by naloxone in the neurons in which it was applied. DAMGO also decreased the frequency of spontaneous PSPs in 13 neurons, 7 of which were also hyperpolarized by DAMGO. Five of the seven hyperpolarized neurons were nociceptive, responding to both heat and mechanically noxious stimuli, whereas two responded to slow, innocuous brush. These results indicate that whole cell, tight seal recordings sample a similar population of lamina I and II neurons in the rat as those found with sharp electrode recordings in cat and monkey. They further indicate that DAMGO hyperpolarizes a subset of the nociceptive neurons that have input from both heat and mechanical nociceptors and that presynaptic DAMGO effects can be observed in nociceptive neurons that are not hyperpolarized by DAMGO.
α-Latrocrustatoxin Increases Neurotransmitter Release by Activating a Calcium Influx Pathway at Crayfish Neuromuscular Junction
Authors: Elrick Donald B. , Charlton Milton P.
Published: December 2017

α-latrocrustatoxin (α-LCTX), a component of black widow spider venom (BWSV), produced a 50-fold increase in the frequency of spontaneously occurring miniature excitatory postsynaptic potentials (mEPSPs) at crayfish neuromuscular junctions but did not alter their amplitude distribution. During toxin action, periods of high-frequency mEPSP discharge were punctuated by periods in which mEPSP frequency returned toward control levels. EPSPs were increased in amplitude during periods of enhanced mEPSP discharge. α-LCTX had no effect when applied in Ca2+-free saline, but subsequent addition of Ca2+ caused an immediate enhancement of mEPSP frequency even when α-LCTX was previously washed out of the bath with Ca2+-free saline. Furthermore removal of Ca2+from the saline after α-LCTX had elicited an effect immediately blocked the action on mEPSP frequency. Thus α-LCTX binding is insensitive to Ca2+, but toxin action requires extracellular Ca2+ ions. Preincubation with wheat germ agglutinin prevented the effect of α-LCTX but not its binding. These binding characteristics suggest that the toxin may bind to a crustacean homologue of latrophilin/calcium-independent receptor for latrotoxin, a G-protein-coupled receptor for α-latrotoxin (α-LTX) found in vertebrates. α-LCTX caused “prefacilitation” of EPSP amplitudes, i.e., the first EPSP in a train was enhanced in amplitude to a greater degree than subsequent EPSPs. A similar alteration in the pattern of facilitation was observed after application of the Ca2+ionophore, A23187, indicating that influx of Ca2+ may mediate the action of α-LCTX. In nerve terminals filled with the Ca2+ indicator, calcium green 1, α-LCTX caused increases in the fluorescence of the indicator that lasted for several minutes before returning to rest. Neither fluorescence changes nor toxin action on mEPSP frequency were affected by the Ca2+ channel blockers ω-agatoxin IVA or Cd2+, demonstrating that Ca2+ influx does not occur via Ca2+ channels normally coupled to transmitter release in this preparation. The actions of α-LCTX could be reduced dramatically by intracellular application of the Ca2+ chelator, bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid. We conclude that induction of extracellular Ca2+influx into nerve terminals is sufficient to explain the action of α-LCTX on both spontaneous and evoked transmitter release at crayfish neuromuscular junctions.
Coding of Locomotor Phase in Populations of Neurons in Rostral and Caudal Segments of the Neonatal Rat Lumbar Spinal Cord
Authors: Tresch Matthew C. , Kiehn Ole
Published: December 2017

Several experiments have demonstrated that rostral segments of the vertebrate lumbar spinal cord produce a rhythmic motor output more readily and of better quality than caudal segments. Here we examine how this rostrocaudal gradient of rhythmogenic capability is reflected in the spike activity of neurons in the rostral (L2) and caudal (L5) lumbar spinal cord of the neonatal rat. The spike activity of interneurons in the ventromedial cord, a region necessary for the production of locomotion, was recorded intracellularly with patch electrodes and extracellularly with tetrodes during pharmacologically induced locomotion. Both L2 and L5 neurons tended to be active in phase with their homologous ventral root. L5 neurons, however, had a wider distribution of their preferred phases of activity throughout the locomotor cycle than L2 neurons. The strength of modulation of the activity of individual L2 neurons was also larger than that of L5 neurons. These differences resulted in a stronger rhythmic signal from the L2 neuronal population than from the L5 population. These results demonstrate that the rhythmogenic capability of each spinal segment was reflected in the activity of interneurons located in the same segment. In addition to paralleling the rostrocaudal gradient of rhythmogenic capability, these results further suggest a colocalization of motoneurons and their associated interneurons involved in the production of locomotion.
Gender Differences in the Fatigability of Human Skeletal Muscle
Authors: Semmler John G. , Kutzscher Devin V. , Enoka Roger M.
Published: December 2017

After participating in a 4-wk intervention that reduced normal usage of the elbow flexor muscles, all six women, but only one of six men, experienced a marked increase in the endurance time during a low-force fatiguing contraction. The increase in endurance time was associated with an altered pattern of muscle activation that did not involve the commonly observed progressive increase in muscle activity. Rather, the muscle activity comprised intermittent motor unit activity. In those individuals who exhibited this behavior, the novel pattern of muscle activity was only present immediately after 4 wk of limb immobilization and not before the intervention or after 4 wk of recovery. These findings suggest possible differences between women and men in the adaptations of the neuromuscular system.
Induction of NMDA Receptor-Dependent Long-Term Depression in Visual Cortex Does Not Require Metabotropic Glutamate Receptors
Authors: Sawtell Nathaniel B. , Huber Kimberly M. , Roder John C. , Bear Mark F.
Published: December 2017

We tested the role of group I mGluRs in the induction of long-term depression (LTD) in the visual cortex, using the novel mGluR antagonist LY341495 and mice lacking mGluR5, the predominant phosphoinositide (PI)-linked mGluR in the visual cortex. We find that LY341495 is a potent blocker of glutamate-stimulated PI hydrolysis in visual cortical synaptoneurosomes, and that it effectively antagonizes the actions of the mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on synaptic transmission in visual cortical slices. However, LY341495 has no effect on the induction of LTD by low-frequency stimulation. Furthermore, mice lacking mGluR5 show normal NMDA receptor-dependent LTD. These results indicate that group I mGluR activation is not required for the induction of NMDA receptor-dependent LTD in the visual cortex.
Modulation of Fictive Feeding by Dopamine and Serotonin inAplysia
Authors: Kabotyanski Evgeni A. , Baxter Douglas A. , Cushman Susan J. , Byrne John H.
Published: December 2017

The buccal ganglia of Aplysia contain a central pattern generator (CPG) that mediates rhythmic movements of the buccal apparatus during feeding. Activity in this CPG is believed to be regulated, in part, by extrinsic serotonergic inputs and by an intrinsic and extrinsic system of putative dopaminergic cells. The present study investigated the roles of dopamine (DA) and serotonin (5-HT) in regulating feeding movements of the buccal apparatus and properties of the underlying neural circuitry. Perfusing a semi-intact head preparation with DA (50 μM) or the metabolic precursor of catecholamines (l-3–4-dihydroxyphenylalanine, DOPA, 250 μM) induced feeding-like movements of the jaws and radula/odontophore. These DA-induced movements were similar to bites in intact animals. Perfusing with 5-HT (5 μM) also induced feeding-like movements, but the 5-HT-induced movements were similar to swallows. In preparations of isolated buccal ganglia, buccal motor programs (BMPs) that represented at least two different aspects of fictive feeding (i.e., ingestion and rejection) could be recorded. Bath application of DA (50 μM) increased the frequency of BMPs, in part, by increasing the number of ingestion-like BMPs. Bath application of 5-HT (5 μM) did not significantly increase the frequency of BMPs nor did it significantly increase the proportion of ingestion-like BMPs being expressed. Many of the cells and synaptic connections within the CPG appeared to be modulated by DA or 5-HT. For example, bath application of DA decreased the excitability of cells B4/5 and B34, which in turn may have contributed to the DA-induced increase in ingestion-like BMPs. In summary, bite-like movements were induced by DA in the semi-intact preparation, and neural correlates of these DA-induced effects were manifest as an increase in ingestion-like BMPs in the isolated ganglia. Swallow-like movements were induced by 5-HT in the semi-intact preparation. Neural correlates of these 5-HT-induced effects were not evident in isolated buccal ganglia, however.
Comparing Extraocular Motoneuron Discharges During Head-Restrained Saccades and Head-Unrestrained Gaze Shifts
Authors: Cullen Kathleen E. , Galiana Henrietta L. , Sylvestre Pierre A.
Published: December 2017

Burst neurons (BNs) in the paramedian pontine reticular formation provide the primary input to the extraocular motoneurons (MNs) during head-restrained saccades and combined eye-head gaze shifts. Prior studies have shown that BNs carry eye movement–related signals during saccades and carry head as well as eye movement–related signals during gaze shifts. Therefore MNs receive signals related to head motion during gaze shifts, yet they solely drive eye motion. Here we addressed whether the relationship between MN firing rates and eye movements is influenced by the additional premotor signals present during gaze shifts. Neurons in the abducens nucleus of monkeys were first studied during saccades made with the head stationary. We then recorded from the same neurons during voluntary combined eye-head gaze shifts. We conclude that the activity of MNs, in contrast to that of BNs, is related to eye motion by the same dynamic relationship during head-restrained saccades and head-unrestrained gaze shifts. In addition, we show that a standard metric-based analysis [i.e., counting the number of spikes (NOS) in a burst] yields misleading results when applied to the same data set. We argue that this latter approach fails because it does not properly consider the system's dynamics or the strong interactions between eye and head motion.
Characteristics of Plateau Activity During the Latent Period Prior to Epileptiform Discharges in Slices From Rat Piriform Cortex
Authors: Demir Rezan , Haberly Lewis B. , Jackson Meyer B.
Published: December 2017

The deep piriform region has an unusually high seizure susceptibility. Voltage imaging previously located the sites of epileptiform discharge onset in slices of rat piriform cortex and revealed the spatiotemporal pattern of development of two types of electrical activity during the latent period prior to discharge onset. A ramplike depolarization (onset activity) appears at the site of discharge onset. Onset activity is preceded by a sustained low-amplitude depolarization (plateau activity) at another site, which shows little if any overlap with the site of onset. Because synaptic blockade at either of these two sites blocks discharges, it was proposed that both forms of latent period activity are necessary for the generation of epileptiform discharges and that the onset and plateau sites work together in the amplification of electrical activity. The capacity for amplification was examined here by studying subthreshold responses in slices of piriform cortex using two different in vitro models of epilepsy. Under some conditions electrically evoked responses showed a nonlinear dependence on stimulus current, suggesting amplification by strong polysynaptic excitatory responses. The sites of plateau and onset activity were mapped for different in vitro models of epilepsy and different sites of stimulation. These experiments showed that the site of plateau activity expanded into deep layers of neighboring neocortex in parallel with expansions of the onset site into neocortex. These results provide further evidence that interactions between the sites of onset and plateau activity play an important role in the initiation of epileptiform discharges. The site of plateau activity showed little variation with different stimulation sites in the piriform cortex, but when stimulation was applied in the endopiriform nucleus (in the sites of onset of plateau activity), plateau activity had a lower amplitude and became distributed over a much wider area. These results indicate that in the initiation of epileptiform discharges, the location of the circuit that generates plateau activity is not rigidly defined but can exhibit flexibility.
Effect of High Ba2+ on Norepinephrine-Induced Inhibition of N-Type Calcium Current in Bullfrog Sympathetic Neurons
Authors: Lee Hye Kyung , Liu Lian , Elmslie Keith S.
Published: December 2017

The voltage-dependent inhibition of N-type calcium current by neurotransmitters is the best-understood example of neuronal calcium channel inhibition. One of the mechanisms by which this pathway is thought to inhibit the calcium current is by reducing the permeation of divalent cations through the channel. In this study one prediction of this hypothesis was examined, that high concentrations of divalent cations reduce the maximum neurotransmitter-induced inhibition. Norepinephrine (NE)-induced inhibition was compared in external solutions containing either 2 or 100 mM Ba2+. Initially, NE dose-response curves were generated by averaging data from many neurons, and it was found that the relationship was right shifted in the high-Ba2+ external solution without an effect on maximum inhibition. The IC50 was 0.6 and 3 μM in 2 and 100 mM Ba2+, respectively. This shift was verified by comparing the effect of NE on single neurons exposed to both 2 and 100 mM Ba2+. The inhibition induced by 1 μM NE was reduced in 100 mM Ba2+ compared with that in 2 mM Ba2+. However, the response to 100 μM NE was identical between high and low Ba2+. Thus, divalent cations appear to act as a competitive inhibitor of NE binding, which likely results from these ions' interacting with negatively charged amino acids that are important for catecholamine binding to adrenergic receptors. Because the maximum inhibition induced by NE was similar in low and high Ba2+, the effect of inhibition on single N-type calcium channels was not altered by the divalent cation concentration.
Conditioned Eyeblink Response Consists of Two Distinct Components
Authors: Ivarsson Magnus , Svensson Pär
Published: December 2017

The aim of these experiments was to obtain a detailed knowledge of how the orbicularis oculi muscle is activated during the execution of a conditioned eyeblink response (CR). This is the first critical step to understand the underlying neural mechanisms involved in the control of the CR. Decerebrate ferrets were trained in a classical conditioning paradigm. The conditioned stimulus (CS) was a train of electrical stimuli (15 pulses, 50 Hz, 1 mA) applied to the forelimb, and the unconditioned stimulus (US) was a train of electrical stimuli (3 pulses, 50 Hz, 3–4 mA) to the periorbital region. The CRs were studied by recording electromyograms (EMGs) from the orbicularis oculi muscle. The eyeblink CR in all animals showed a similar topography with at least two different components, CR1 and CR2, which were expressed at different rates. CR1 appeared first during acquisition, had a shorter onset latency, and was more phasic and more resistant to extinction than CR2. A marked pause in the muscle activity separated the two components. To control that the two-component CR were not species, paradigm or preparation specific, awake rabbits were trained with a tone CS (300 ms, 4 kHz, 64 dB) and a train of periorbital stimuli as US (3 pulses, 50 Hz, 3 mA). CR1 and CR2 were present in the rabbit eyeblink CR. The cerebellum is implicated in the control of CRs and to study whether separate neural pathways were responsible for CR1 and CR2, direct brachium pontis stimulation was used to replace the forelimb CS. CR1 and CR2 were present in the CR elicited by the brachium pontis CS. The presence of CR1 and CR2 after a unilateral lesion of the brachium conjunctivum shows that output from the contralateral cerebellar hemisphere was not the cause for any of the components. Other mechanisms that might be involved in the separation of the CR into two components are discussed. The results show that the eyeblink CR consists of at least two components, CR1 and CR2, which most likely originate either as a direct central command from the cerebellum or in the output pathway before the facial nucleus.
Directionality Derived From Pinna-Cue Spectral Notches in Cat Dorsal Cochlear Nucleus
Authors: Imig Thomas J. , Bibikov Nikolai G. , Poirier Pierre , Samson Frank K.
Published: December 2017

We tested two hypotheses to determine whether dorsal cochlear nucleus (DCN) neurons are specialized to derive directionality from spectral notches: DCN neurons exhibit greater spectral-dependent directionality than ventral cochlear nucleus (VCN) neurons, and spectral-dependent directionality depends on response minima (nulls) produced by coincidence of best frequency (BF) and spectral-notch center frequency. Single-unit responses to 50-ms noise and tone bursts were recorded in barbiturate-anesthetized cats (BFs: 4–37 kHz). Units were classified using BF tone poststimulus time histograms. Pauser, onset-G (type II interneurons), and some chopper units were recorded from the DCN. Primary-like, onset-CIL (onset other than onset-G), and most choppers in the sample were recorded from the VCN. Many pauser and onset-G units were highly directional to noise. Chopper, onset-CIL, and primary-like units (collectively referred to as C-O-P units) were not. The difference in directionality depends on a monaural mechanism as pausers were more directional to monaural noise than C-O-P units. Contralateral inhibition produced a small increase in pauser directionality to noise simulation but had no effect on directionality of C-O-P units. Pauser and C-O-P units exhibited similar low directionality to BF tone, showing that the difference in noise directionality between groups depends on spectral cues. These results show that spectral-dependent directionality is a DCN specialization. Azimuth functions of highly directional units exhibited response nulls, and there was a linear relationship between BFs in the range of 8–13 kHz and azimuthal locations of nulls. This relationship parallels the known spatial distribution of spectral-notch center frequencies on the horizontal plane. Furthermore spatial receptive fields of pausers show response nulls that follow the expected diagonal trajectory of the spectral notch in this frequency range. These results show that DCN spectral-dependent directionality depends on response nulls produced by coincidence of unit BF and spectral-notch center-frequency.
Pharmacological Evidence of Inhibitory and Disinhibitory Neuronal Circuits in Dorsal Cochlear Nucleus
Authors: Davis Kevin A. , Young Eric D.
Published: December 2017

The dorsal cochlear nucleus (DCN) is rich in both glycine and GABA inhibitory neurotransmitter systems, and the response properties of its principal cells (pyramidal and giant cells) are strongly shaped by inhibitory inputs. For example, DCN principal cells often display highly nonmonotonic (so-called type IV) input-output functions in response to best-frequency (BF) tones. In this study, the inhibitory inputs onto the principal cell types and onto response types of known inhibitory interneurons were compared before and during iontophoretic application of the glycine- and GABAA-receptor antagonists, strychnine and bicuculline. Strychnine eliminates the central (on-BF) inhibitory area in type IV units, resulting in monotonic BF rate-level curves. Unexpectedly, bicuculline primarily enhances inhibition in principal-cell types; for example, type IV units are inhibited at lower sound levels in the presence of bicuculline. Principal cell types with weaker inhibitory inputs (type IV-T and type III units) are more strongly inhibited in the presence of bicuculline and usually are converted into type IV units. This enhancement of on-BF inhibition by bicuculline suggests a disinhibitory process involving GABAA action on a non-GABAAergic inhibitory pathway. This latter pathway is probably glycinergic and involves type II units (deep-layer vertical cells) and/or complex-spiking units (superficial cartwheel cells) because both of these unit types are disinhibited by bicuculline. One intrinsic GABAA source could be the superficial stellate cells in DCN because bicuculline partly blocks the inhibition evoked by somatosensory-stimulated activation of the superficial granule-cell circuitry in DCN. Taken together, the results suggest that glycinergic circuits mediate directly the inhibition of DCN principal cells, but that GABAAergic circuits modulate the strength of the inhibition.
Silent NMDA Receptor–Mediated Synapses Are Developmentally Regulated in the Dorsal Horn of the Rat Spinal Cord
Authors: Baba Hiroshi , Doubell Timothy P. , Moore Kimberly A. , Woolf Clifford J.
Published: December 2017

In vitro whole cell patch-clamp recording techniques were utilized to study silent pure– N-methyl-d-aspartate (NMDA) receptor–mediated synaptic responses in lamina II (substantia gelatinosa, SG) and lamina III of the spinal dorsal horn. To clarify whether these synapses are present in the adult and contribute to neuropathic pain, transverse lumbar spinal cord slices were prepared from neonatal, naive adult and adult sciatic nerve transected rats. In neonatal rats, pure-NMDA receptor–mediated excitatory postsynaptic currents (EPSCs) were elicited in SG neurons either by focal intraspinal stimulation ( n = 15 of 20 neurons) or focal stimulation of the dorsal root ( n = 2 of 7 neurons). In contrast, in slices from naive adult rats, no silent pure-NMDA EPSCs were recorded in SG neurons following focal intraspinal stimulation ( n = 27), and only one pure-NMDA EPSC was observed in lamina III ( n = 23). Furthermore, in rats with chronic sciatic nerve transection, pure-NMDA EPSCs were elicited by focal intraspinal stimulation in only 2 of 45 SG neurons. Although a large increase in Aβ fiber evoked mixed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptor–mediated synapses was detected after sciatic nerve injury, Aβ fiber–mediated pure-NMDA EPSCs were not evoked in SG neurons by dorsal root stimulation. Pure-NMDA receptor–mediated EPSCs are therefore a transient, developmentally regulated phenomenon, and, although they may have a role in synaptic refinement in the immature dorsal horn, they are unlikely to be involved in receptive field plasticity in the adult.
Effects of Intracolonic Opioid Receptor Agonists on Polymodal Pelvic Nerve Afferent Fibers in the Rat
Authors: Su X. , Julia V. , Gebhart G. F.
Published: December 2017

We studied the effects of intracolonic administration of opioid receptor agonists (ORAs) on responses of pelvic nerve afferent fibers to colorectal distension (CRD) and heat. Single-fiber recordings were made from the decentralized S1 dorsal rootlet in the rat. An ∼7-cm length of descending colon was isolated in situ to permit intracolonic perfusion with Krebs solution, which, when the outflow was clamped, was used to distend the colon. Responses to noxious CRD (40 mmHg, 30 s) were tested after intracolonic instillation of μ-, δ- or κ-ORAs. Intracolonic administration of the κ-ORAs EMD 61,753 ( n = 5/12) and U62,066 ( n = 8/11), but not either the μ-ORA fentanyl or the δ-ORA SNC-80, concentration-dependently inhibited responses of afferent fibers. For fibers unaffected by intracolonic administration of EMD 61,753 or U62,066, intra-arterial administration of κ-ORAs was effective. Forty-one of 54 mechanosensitive fibers also responded to intracolonic instillation of heated Krebs solution (50°C). Intra-arterial injection of fentanyl or SNC-80 did not attenuate responses to heat. Either intracolonic or intra-arterial administration of EMD 61,753 or U62,066, however, inhibited afferent fiber responses to heat. These results document that mechanical and thermal sensitivity of polymodal pelvic nerve afferent fibers innervating the rat colon can be inhibited peripherally by intracolonic instillation of κ-ORAs.
Competition Between Internal AlF4−and Receptor-Mediated Stimulation of Dorsal Raphe Neuron G-Proteins Coupled to Calcium Current Inhibition
Authors: Chen Yuan , Penington Nicholas J.
Published: December 2017

Intracellular aluminum fluoride (AlF4−), placed in a patch pipette, activated a G-protein, resulting in a “tonic” inhibition of the Ca2+current of isolated serotonergic neurons of the rat dorsal raphe nucleus. Serotonin (5-HT) also inhibits the Ca2+current of these cells. After external bath application and quick removal of 5-HT to an AlF4−containing cell, there was a reversal or transient disinhibition (TD) of the inhibitory effect of AlF4−on Ca2+current. A short predepolarization of the membrane potential to +70 mV, a condition that is known to reverse G-protein–mediated inhibition, reversed the inhibitory effect of AlF4−on Ca2+current and brought the Ca2+current to the same level as that seen at the peak of the TD current. With AlF4−in the pipette, the TD phenomenon could be eliminated by lowering pipette MgATP, or by totally chelating pipette Al3+. In the presence of AlF4−, but with either lowered MgATP or extreme efforts to eliminate pipette Al3+, the rate of recovery from 5-HT on wash was slowed, a condition opposite to that where a TD occurred. The putative complex of AlF4−-bound G-protein (Gα·GDP·AlF4−) appeared to free G-βγ-subunits, mimicking the effect on Ca2+channels of the G·GTP complex. The on-rate of the inhibition of Ca2+current, after a depolarizing pulse, by βγ-subunits released by AlF4−in the pipette was significantly slower than that of the agonist-activated G-protein. Theoff-rate of the AlF4−-mediated inhibition in response to a depolarizing pulse, a measure of the affinity of the free G-βγ-subunit for the Ca2+channel, was slightly slower than that of the agonist stimulated G-protein. In summary, AlF4−modified the off-rate kinetics of G-protein activation by agonists, but had little effect on the kinetics of the interaction of the βγ-subunit with Ca2+channels. Agonist application temporarily reversed the effects of AlF4−, making it a complementary tool to GTP-γ-S for the study of G-protein interactions.
Escape Swim Network Interneurons Have Diverse Roles in Behavioral Switching and Putative Arousal inPleurobranchaea
Authors: Jing Jian , Gillette Rhanor
Published: December 2017

Escape swimming in the predatory sea slug Pleurobranchaea is a dominant behavior that overrides feeding, a behavioral switch caused by swim-induced inhibition of feeding command neurons. We have now found distinct roles for the different swim interneurons in acute suppression of feeding during the swim and in a longer-term stimulation of excitability in the feeding network. The identified pattern-generating swim neurons A1, A3, A10, and their follower interneuron A-ci1, suppress feeding motor output partly by excitation of the I1 feeding interneurons, which monosynaptically inhibit both the feeding command neurons, PCP, PSE, and other major interneurons, the I2s. This mechanism exerts broad inhibition of the feeding network suitable to an escape response; broader than feeding suppression in learned and satiation-induced food avoidance and acting through a different presynaptic pathway. Four intrinsic neuromodulatory neurons of the swim network, the serotonergic As1–4, add little to direct suppression of feeding. Rather, they monosynaptically excite the serotonergic metacerebral giant (MCG) neurons of the feeding network, themselves intrinsic neuromodulators of feeding, as well as a cluster of adjacent serotonergic feeding neurons, with both fast and slow EPSPs. They also provide mild neuromodulatory excitation of the PCP/PSE feeding command neurons, and I1 and I2 feeding interneurons, which is masked by inhibition during the swim. As1–4 also excite the serotonergic pedal ganglion G neurons for creeping locomotion. These observations further delineate the nature of the putative serotonergic arousal system of gastropods and suggest a central coordinating role to As1–4.
Stochastic Resonance Improves Signal Detection in Hippocampal CA1 Neurons
Authors: Stacey William C. , Durand Dominique M.
Published: December 2017

Stochastic resonance (SR) is a phenomenon observed in nonlinear systems whereby the introduction of noise enhances the detection of a subthreshold signal for a certain range of noise intensity. The nonlinear threshold detection mechanism that neurons employ and the noisy environment in which they reside makes it likely that SR plays a role in neural signal detection. Although the role of SR in sensory neural systems has been studied extensively, its role in central neurons is unknown. In many central neurons, such as the hippocampal CA1 cell, very large dendritic trees are responsible for detecting neural input in a noisy environment. Attenuation due to the electrotonic length of these trees is significant, suggesting that a method other than passive summation is necessary if signals at the distal ends of the tree are to be detected. The hypothesis that SR plays an important role in the detection of distal synaptic inputs first was tested in a computer simulation of a CA1 cell and then verified with in vitro rat hippocampal slices. The results clearly showed that SR can enhance signal detection in CA1 hippocampal cells. Moreover, high levels of noise were found to equalize detection of synaptic signals received at varying positions on the dendritic tree. The amount of noise needed to evoke the effect is compared with physiological noise in slices and in vivo.
Striatal Nitric Oxide Signaling Regulates the Neuronal Activity of Midbrain Dopamine Neurons In Vivo
Authors: West Anthony R. , Grace Anthony A.
Published: December 2017

A major component of the cortical regulation of the nigrostriatal dopamine (DA) system is known to occur via activation of striatal efferent systems projecting to the substantia nigra. The potential intermediary role of striatal nitric oxide synthase (NOS)-containing interneurons in modulating the efferent regulation of DA neuron activity was examined using single-unit recordings of DA neurons performed concurrently with striatal microdialysis in anesthetized rats. The response of DA neurons recorded in the substantia nigra to intrastriatal artificial cerebrospinal fluid (ACSF) or drug infusion was examined in terms of mean firing rate, percent of spikes fired in bursts, cells/track, and response to electrical stimulation of the orbital prefrontal cortex (oPFC) and striatum. Intrastriatal infusion of NOS substrate concurrently with intermittent periods of striatal and cortical stimulation increased the mean DA cell population firing rate as compared with ACSF controls. This effect was reproduced via intrastriatal infusion of a NO generator. Infusion of either a NOS inhibitor or NO chelator via reverse microdialysis did not affect basal firing rate but increased the percentage of DA neurons responding to striatal stimulation with an initial inhibition followed by a rebound excitation (IE response) from 40 to 74%. NO scavenger infusion also markedly decreased the stimulation intensity required to elicit an IE response to electrical stimulation of the striatum. In single neurons in which the effects of electrical stimulation were observed before and after drug delivery, NO antagonist infusion was observed to decrease the onset latency and extend the duration of the initial inhibitory phase induced by either oPFC or striatal stimulation. This is the first report showing that striatal NO tone regulates the basal activity and responsiveness of DA neurons to cortical and striatal inputs. These studies also indicate that striatal NO signaling may play an important role in the integration of information transmitted to basal ganglia output centers via corticostriatal and striatal efferent pathways.
Frequency and Intensity Response Properties of Single Neurons in the Auditory Cortex of the Behaving Macaque Monkey
Authors: Recanzone Gregg H. , Guard Darren C. , Phan Mimi L.
Published: December 2017

Response properties of auditory cortical neurons measured in anesthetized preparations have provided important information on the physiological differences between neurons in different auditory cortical areas. Studies in the awake animal, however, have been much less common, and the physiological differences noted may reflect differences in the influence of anesthetics on neurons in different cortical areas. Because the behaving monkey is gaining popularity as an animal model in studies exploring auditory cortical function, it has become critical to physiologically define the response properties of auditory cortical neurons in this preparation. This study documents the response properties of single cortical neurons in the primary and surrounding auditory cortical fields in monkeys performing an auditory discrimination task. We found that neurons with the shortest latencies were located in the primary auditory cortex (AI). Neurons in the rostral field had the longest latencies and the narrowest intensity and frequency tuning, neurons in the caudomedial field had the broadest frequency tuning, and neurons in the lateral field had the most monotonic rate/level functions of the four cortical areas studied. These trends were revealed by comparing response properties across the population of studied neurons, but there was considerable variability between neurons for each response parameter other than characteristic frequency (CF) in each cortical area. Although the neuronal CFs showed a systematic spatial organization across AI, no such systematic organization was apparent for any other response property in AI or the adjacent cortical areas. The results of this study indicate that there are physiological differences between auditory cortical fields in the behaving monkey consistent with previous studies in the anesthetized animal and provide insights into the functional role of these cortical areas in processing acoustic information.
Macaque Supplementary Eye Field Neurons Encode Object-Centered Locations Relative to Both Continuous and Discontinuous Objects
Authors: Olson Carl R. , Tremblay Léon
Published: December 2017

Many neurons in the supplementary eye field (SEF) of the macaque monkey fire at different rates before eye movements to the right or the left end of a horizontal bar regardless of the bar's location in the visual field. We refer to such neurons as carrying object-centered directional signals. The aim of the present study was to throw light on the nature of object-centered direction selectivity by determining whether it depends on the reference image's physical continuity. To address this issue, we recorded from 143 neurons in two monkeys. All of these neurons were located in a region coincident with the SEF as mapped out in previous electrical stimulation studies and many exhibited task-related activity in a standard saccade task. In each neuron, we compared neuronal activity across trials in which the monkey made eye movements to the right or left end of a reference image. On interleaved trials, the reference image might be either a horizontal bar or a pair of discrete dots in a horizontal array. The dominant effect revealed by this experiment was that neurons selectively active before eye movements to the right (or left) end of a bar were also selectively active before eye movements to the right (or left) dot in a horizontal array. An additional minor effect, present in around a quarter of the sample, took the form of a difference in firing rate between bar and dot trials, with the greater level of activity most commonly associated with dot trials. These phenomena could not be accounted for by minor intertrial differences in the physical directions of eye movements. In summary, SEF neurons carry object-centered signals and carry these signals regardless of whether the reference image is physically continuous or disjunct.
Locomotor Network Maturation Is Transiently Delayed in the MAOA-Deficient Mouse
Authors: Cazalets Jean-René , Gardette Marie , Hilaire Gérard
Published: December 2017

In vivo and in vitro experiments were performed in control (C3H) and monoamine oxidase A (MAOA)-deficient (Tg8) neonatal mice to determine whether MAOA deficiency affected spinal locomotor network maturation. Comparing the swimming behaviors at birth in C3H mice with those in Tg8 mice revealed a delayed role for the hindlimbs in Tg8 swimming, even though adult swimming behavior was acquired at postnatal day 14 (P14) in both strains. Analyzing the locomotor network activity in vitro showed that serotonin (5-HT) induced and modulated locomotor-like discharges in hindlimb ventral roots of C3H but not Tg8 neonates. The Tg8 network began, however, to be affected by 5-HT at P11. Thus both in vivo and in vitro results argue for a transient delay of locomotor network maturation in the Tg8 strain.
Presynaptic and Interactive Peptidergic Modulation of Reticulospinal Synaptic Inputs in the Lamprey
Authors: Parker David
Published: December 2017

The modulatory effects of neuropeptides on descending inputs to the spinal cord have been examined by making paired recordings from reticulospinal axons and spinal neurons in the lamprey. Four peptides were examined; peptide YY (PYY) and cholecystokinin (CCK), which are contained in brain stem reticulospinal neurons, and calcitonin-gene–related peptide (CGRP) and neuropeptide Y (NPY), which are contained in primary afferents and sensory interneurons, respectively. Each of the peptides reduced the amplitude of monosynaptic reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The modulation appeared to be presynaptic, because postsynaptic input resistance and membrane potential, the amplitude of the electrical component of the EPSP, postsynaptic responses to glutamate, and spontaneous miniature EPSP amplitudes were unaffected. In addition, none of the peptides affected the pattern of N-methyl-d-aspartate (NMDA)–evoked locomotor activity in the isolated spinal cord. Potential interactions between the peptides were also examined. The “brain stem peptides” CCK and PYY had additive inhibitory effects on reticulospinal inputs, as did the “sensory peptides” CGRP and NPY. Brain stem peptides also had additive inhibitory effects when applied with sensory peptides. However, sensory peptides increased or failed to affect the amplitude of reticulospinal inputs in the presence of the brain stem peptides. These interactive effects also appear to be mediated presynaptically. The functional consequence of the peptidergic modulation was investigated by examining spinal ventral root responses elicited by brain stem stimulation. CCK and CGRP both reduced ventral root responses, although in interaction both increased the response. These results thus suggest that neuropeptides presynaptically influence the descending activation of spinal locomotor networks, and that they can have additive or novel interactive effects depending on the peptides examined and the order of their application.
Novel Mechanism of Inhibition by the P2 Receptor Antagonist PPADS of ATP-Activated Current in Dorsal Root Ganglion Neurons
Authors: Li Chaoying
Published: December 2017

The antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) has been proposed to selectively antagonize the actions of ATP at P2X receptors. Whole cell patch-clamp recording techniques therefore were used to characterize PPADS inhibition of ATP-activated current in bullfrog dorsal root ganglion (DRG) neurons. PPADS, 0.5–10 μM, inhibited ATP-activated current in a concentration-dependent manner with an IC50 of 2.5 ± 0.03 μM. PPADS produced a gradual decline of ATP-activated current to a steady state, but this was not an indication of use dependence as the gradual declining component could be eliminated by exposure to PPADS before ATP application. In addition, ATP-activated current recovered completely from inhibition by PPADS in the absence of agonist. The slow onset of inhibition by PPADS was not apparently due to an action at an intracellular site as inclusion of 10 μM PPADS in the recording pipette neither affected the ATP response nor did it alter inhibition of the ATP response when 2.5 μM PPADS was applied externally. PPADS, 2.5 μM, decreased the maximal response to ATP by 51% without changing its EC50. PPADS inhibition of ATP-activated current was independent of membrane potential between −80 and +40 mV and did not involve a shift in the reversal potential of the current. The magnitude of PPADS inhibition of ATP-activated current was dependent on the duration of the prior exposure to PPADS. The time constants of both onset and offset of PPADS inhibition of ATP-activated current did not differ significantly with changes in ATP concentration from 1 to 5 μM. Recovery of ATP-activated current from PPADS inhibition also exhibited a slow phase that was not accelerated by the presence of agonist and was dependent on the concentration of PPADS. The apparent dissociation rate of PPADS from unliganded ATP-gated ion channels was much greater than the rate of the slow phase of recovery of ATP-activated current from PPADS inhibition. The results suggest that PPADS can inhibit P2X receptor function in a complex noncompetitive manner. PPADS produces a long-lasting inhibition that does not appear to result from open channel block but rather from an action at an allosteric site apparently accessible from the extracellular environment that involves a greatly reduced rate of dissociation from liganded versus unliganded ATP-gated ion channels.
Ischemia But Not Anoxia Evokes Vesicular and Ca2+-Independent Glutamate Release In the Dorsal Vagal Complex In Vitro
Authors: Kulik Anna , Trapp Stefan , Ballanyi Klaus
Published: December 2017

Whole cell recordings of fura-2 dialyzed vagal neurons of brain stem slices were used to monitor interstitial glutamate accumulation within the dorsal vagal complex. Anoxia produced a sustained outward current (60 pA) and a moderate [Ca2+]irise (40 nM). These responses were neither mimicked by [1S,3R]-1-aminocyclo-pentane-1,3-dicarboxylic acid nor affected by Ca2+-free solution, 6-cyano-7-nitroquino-xaline-2,3-dione (CNQX), 2-amino-5-phosphonovalerate (APV), or tetrodotoxin. Anoxia or cyanide in glucose-free saline (in vitro ischemia) as well as ouabain or iodoacetate elicited an initial anoxia-like [Ca2+]iincrease that turned after several minutes into a prominent Ca2+transient (0.9 μM) and inward current (−1.8 nA). APV plus CNQX (plus methoxyverapamil) inhibited this inward current as well as accompanying spontaneous synaptic activity, and reduced the secondary [Ca2+]irise to values similar to those during anoxia. Each of the latter drugs delayed onset of both ischemic current and prominent [Ca2+]irise by several minutes and attenuated their magnitudes by up to 40%. Ca2+-free solution induced a twofold delay of the ischemic inward current and suppressed the prominent Ca2+increase but not the initial moderate [Ca2+]irise. Cyclopiazonic acid or arachidonic acid in Ca2+-free saline delayed further the ischemic current, whereas neither inhibitors of glutamate uptake (dihydrokainate,d,l-threo-β-hydroxyaspartate,l-transpyrrolidone-2,4-dicarboxylate) nor the Cl−channel blocker 5-nitro-2-(3-phenylpropyl-amino) benzoic acid had any effect. In summary, the response to metabolic arrest is due to activation of ionotropic glutamate receptors causing Ca2+entry via N-methyl-d-aspartate receptors and voltage-activated Ca2+channels. An early Ca2+-dependent exocytotic phase of ischemic glutamate release is followed by nonvesicular release, not mediated by reversed glutamate uptake or Cl−channels. The results also show that glycolysis prevents glutamate release during anoxia.