bluuebunny/crossref_metadata_2025 huggingface dataset:
Encoding of Visual Information by LGN Bursts
Authors: Reinagel Pamela , Godwin Dwayne , Sherman S. Murray , Koch Christof
Published: December 2017

Encoding of visual information by LGN bursts. Thalamic relay cells respond to visual stimuli either in burst mode, as a result of activation of a low-threshold Ca2+ conductance, or in tonic mode, when this conductance is inactive. We investigated the role of these two response modes for the encoding of the time course of dynamic visual stimuli, based on extracellular recordings of 35 relay cells from the lateral geniculate nucleus of anesthetized cats. We presented a spatially optimized visual stimulus whose contrast fluctuated randomly in time with frequencies of up to 32 Hz. We estimated the visual information in the neural responses using a linear stimulus reconstruction method. Both burst and tonic spikes carried information about stimulus contrast, exceeding one bit per action potential for the highest variance stimuli. The “meaning” of an action potential, i.e., the optimal estimate of the stimulus at times preceding a spike, was similar for burst and tonic spikes. In within-trial comparisons, tonic spikes carried about twice as much information per action potential as bursts, but bursts as unitary events encoded about three times more information per event than tonic spikes. The coding efficiency of a neuron for a particular stimulus is defined as the fraction of the neural coding capacity that carries stimulus information. Based on a lower bound estimate of coding efficiency, bursts had ∼1.5-fold higher efficiency than tonic spikes, or 3-fold if bursts were considered unitary events. Our main conclusion is that both bursts and tonic spikes encode stimulus information efficiently, which rules out the hypothesis that bursts are nonvisual responses.
Neural Representation of the Taste of NaCl and KCl in Gustatory Neurons of the Hamster Solitary Nucleus
Authors: Boughter John D. , St. John Steven J. , Smith David V.
Published: December 2017

Neural representation of the taste of NaCl and KCl in gustatory neurons of the hamster solitary nucleus. NaCl and KCl are monovalent salts that can be discriminated behaviorally by hamsters on the basis of their tastes. We examined the effects of the passive Na+ channel blocker amiloride on responses to both of these salts in 34 taste-responsive neurons of the nucleus of the solitary tract (NST) in the hamster. The effects of amiloride were assessed with two different, commonly employed stimulus protocols. Additionally, concentration-response functions for each salt were measured in 37 neurons. Cells were characterized by their best response to (in M) 0.03 NaCl, 0.1 sucrose, 0.003 HCl, 0.001 quinine hydrochloride, and 0.1 KCl. In neurons classified as NaCl-best, amiloride reversibly blocked responses to both NaCl and KCl. In neurons classified as HCl-best, amiloride had no effect on either stimulus. In sucrose-best neurons, amiloride blocked the response to NaCl but not KCl. These results support the hypothesis that both salts are transduced by at least two different receptor mechanisms. In the NST, information arising from these different inputs is maintained in discrete populations of neurons. In addition to differences in amiloride sensitivity, the cell types also differed in their responses to the salts across concentration. At midrange salt concentrations, NaCl-best neurons were far more responsive to NaCl than KCl, whereas HCl- and sucrose-best neurons responded equivalently to the two salts at all concentrations. Because NaCl- and HCl-best cells cannot by themselves distinguish NaCl from KCl, it is the relative activity across these cell types that comprises the code for taste discrimination.
SA1 and RA Receptive Fields, Response Variability, and Population Responses Mapped with a Probe Array
Authors: Vega-Bermudez F. , Johnson K. O.
Published: December 2017

SA1 and RA receptive fields, response variability, and population responses mapped with a probe array. Twenty-four slowly adapting type 1 (SA1) and 26 rapidly adapting (RA) cutaneous mechanoreceptive afferents in the rhesus monkey were studied with an array of independently controlled, punctate probes that covered an entire fingerpad. Each afferent had a receptive field (RF) on a single fingerpad and was studied at 73 skin sites (50 mm2). The entire array was lowered to 1.6 mm below the point of initial skin contact (the background indentation) before delivering single-probe indentations. SA1 and RA responses differed in several ways. 1) SA1 RF boundaries were affected much less by indentation depth than were RA boundaries, and the SA1 RF areas were much more uniform in size. The mean SA1 RF area grew from 5.1 to 8.8 mm2 as the indentation depth increased from 50 to 500 μm; the mean RA RF area grew from 5.5 to 22.4 mm2 over the same intensity range. 2) SA1 RFs were more elongated than RA RFs. Elongated RFs were oriented in all directions relative to the skin ridges and the finger axis. 3) SA1 impulse rates were linear functions of indentation depth at all probe locations in the RF; RA responses tended toward saturation beginning at 100 μm indentation depth when the probe was over the HS. Similarities between SA1 and RA responses were that 1) both were extremely repeatable with SDs < 1 impulse per trial and 2) both had population responses (number of impulses) that were nearly linear functions of indentation depth. However, SA1s represented increasing indentation depth by increasing impulse rates in a small, relatively constant group of afferents, whereas the RAs represented increasing indentation depth predominantly by the recruitment of new afferents at a distance.
Surround Suppression in the Responses of Primate SA1 and RA Mechanoreceptive Afferents Mapped with a Probe Array
Authors: Vega-Bermudez F. , Johnson K. O.
Published: December 2017

Surround suppression in the responses of primate SA1 and RA mechanoreceptive afferents mapped with a probe array. Twenty-four slowly adapting type 1 (SA1) and 26 rapidly adapting (RA) cutaneous mechanoreceptive afferents in the rhesus monkey were studied with an array of independently controlled, punctate probes that covered an entire fingerpad. Each afferent had a receptive field (RF) on a single fingerpad and was studied at 73 skin sites (50 mm2). The entire array was lowered to 1.6 to 3.0 mm below the point of initial skin contact (the background indentation) before delivering indentations with one to seven probes. Indentations were generally limited to 100 μm to minimize gross mechanical interactions. There were two major, new findings. 1) The discharge rates of both SA1 and RA afferents were strongly affected by the number of probes indenting the RF simultaneously. The effect was exponential. Each increase in probe number reduced the response by 24% in SA1 and 12% in RA afferents on average. When seven probes indented the skin simultaneously, the impulse rates in SA1 and RA afferents were reduced to 20 and 40% of the rates evoked by a single probe at the hot spot (all indentations were 100 μm). This shows that before any synaptic interaction in the CNS there is already a mechanism analogous to surround inhibition that suppresses an afferent’s responses to uniform indentation and makes it especially sensitive to deviations from spatial uniformity. 2) The responses of both SA1 and RA afferents were independent of background array depth over the range from 1.6 to 3 mm below the point of initial skin contact. This shows that the neural responses to elements raised above a background are independent of the applied force over a wide range of forces. To relate the background depths to indentation force and to compare humans and monkeys, we studied the biomechanics of indentation with a uniform surface. A remarkable result is that the force-displacement relationships in humans and monkeys were the same; the skin is highly compliant for the first 2–3 mm of indentation and then becomes much stiffer. The results were the same in alert humans and monkeys and in monkeys anesthetized with pentobarbital. Ketamine anesthesia made the skin much stiffer and reduced the compliant range substantially.
Electrical Stimulation of the Horizontal Limb of the Diagonal Band of Broca Modulates Population EPSPs in Piriform Cortex
Authors: Linster Christiane , Wyble Bradley P. , Hasselmo Michael E.
Published: December 2017

Electrical stimulation of the horizontal limb of the diagonal band of Broca modulates population EPSPs in piriform cortex. Electrical stimulation of the horizontal limb of the diagonal band of Broca (HDB) was coupled with recording of evoked potentials in the piriform cortex. Stimulation of the HDB caused an enhancement of the late, disynaptic component of the evoked potential elicited by stimulation of the lateral olfactory tract but caused a suppression of the synaptic potential elicited by stimulation of the posterior piriform cortex. The muscarinic antagonist scopolamine blocked both effects of HDB stimulation. The enhancement of disynaptic potentials could be due to cholinergic depolarization of pyramidal cells, whereas the suppression of potentials evoked by posterior piriform stimulation could be due to presynaptic inhibition of intrinsic fiber synaptic transmission by acetylcholine.
Receptive Fields and Binaural Interactions for Virtual-Space Stimuli in the Cat Inferior Colliculus
Authors: Delgutte Bertrand , Joris Philip X. , Litovsky Ruth Y. , Yin Tom C. T.
Published: December 2017

Receptive fields and binaural interactions for virtual-space stimuli in the cat inferior colliculus. Sound localization depends on multiple acoustic cues such as interaural differences in time (ITD) and level (ILD) and spectral features introduced by the pinnae. Although many neurons in the inferior colliculus (IC) are sensitive to the direction of sound sources in free field, the acoustic cues underlying this sensitivity are unknown. To approach this question, we recorded the responses of IC cells in anesthetized cats to virtual space (VS) stimuli synthesized by filtering noise through head-related transfer functions measured in one cat. These stimuli not only possess natural combinations of ITD, ILD, and spectral cues as in free field but also allow precise control over each cue. VS receptive fields were measured in the horizontal and median vertical planes. The vast majority of cells were sensitive to the azimuth of VS stimuli in the horizontal plane for low to moderate stimulus levels. Two-thirds showed a “contra-preference” receptive field, with a vigorous response on the contralateral side of an edge azimuth. The other third of receptive fields were tuned around a best azimuth. Although edge azimuths of contra-preference cells had a broad distribution, best azimuths of tuned cells were near the midline. About half the cells tested were sensitive to the elevation of VS stimuli along the median sagittal plane by showing either a peak or a trough at a particular elevation. In general receptive fields for VS stimuli were similar to those found in free-field studies of IC neurons, suggesting that VS stimulation provided the essential cues for sound localization. Binaural interactions for VS stimuli were studied by comparing responses to binaural stimulation with responses to monaural stimulation of the contralateral ear. A majority of cells showed either purely inhibitory (BI) or mixed facilitatory/inhibitory (BF&I) interactions. Others showed purely facilitatory (BF) or no interactions (monaural). Binaural interactions were correlated with azimuth sensitivity: most contra-preference cells had either BI or BF&I interactions, whereas tuned cells were usually BF. These correlations demonstrate the importance of binaural interactions for azimuth sensitivity. Nevertheless most monaural cells were azimuth-sensitive, suggesting that monaural cues also play a role. These results suggest that the azimuth of a high-frequency sound source is coded primarily by edges in azimuth receptive fields of a population of ILD-sensitive cells.
Enhancement of the Vestibulo-Ocular Reflex by Prior Eye Movements
Authors: Das Vallabh E. , Dell’Osso Louis F. , Leigh R. John
Published: December 2017

Enhancement of the vestibulo-ocular reflex by prior eye movements. We investigated the effect of visually mediated eye movements made before velocity-step horizontal head rotations in eleven normal human subjects. When subjects viewed a stationary target before and during head rotation, gaze velocity was initially perturbed by ∼20% of head velocity; gaze velocity subsequently declined to zero within ∼300 ms of the stimulus onset. We used a curve-fitting procedure to estimate the dynamic course of the gain throughout the compensatory response to head rotation. This analysis indicated that the median initial gain of compensatory eye movements (mainly because of the vestibulo-ocular reflex, VOR) was 0.8 and subsequently increased to 1.0 after a median interval of 320 ms. When subjects attempted to fixate the remembered location of the target in darkness, the initial perturbation of gaze was similar to during fixation of a visible target (median initial VOR gain 0.8); however, the period during which the gain increased toward 1.0 was >10 times longer than that during visual fixation. When subjects performed horizontal smooth-pursuit eye movements that ended (i.e., 0 gaze velocity) just before the head rotation, the gaze velocity perturbation at the onset of head rotation was absent or small. The initial gain of the VOR had been significantly increased by the prior pursuit movements for all subjects ( P < 0.05; mean increase of 11%). In four subjects, we determined that horizontal saccades and smooth tracking of a head-fixed target (VOR cancellation with eye stationary in the orbit) also increased the initial VOR gain (by a mean of 13%) during subsequent head rotations. However, after vertical saccades or smooth pursuit, the initial gaze perturbation caused by a horizontal head rotation was similar to that which occurred after fixation of a stationary target. We conclude that the initial gain of the VOR during a sudden horizontal head rotation is increased by prior horizontal, but not vertical, visually mediated gaze shifts. We postulate that this “priming” effect of a prior gaze shift on the gain of the VOR occurs at the level of the velocity inputs to the neural integrator subserving horizontal eye movements, where gaze-shifting commands and vestibular signals converge.
Modulation of Stretch Reflexes During Imposed Walking Movements of the Human Ankle
Authors: Kearney Robert E. , Lortie Mireille , Stein Richard B.
Published: December 2017

Modulation of stretch reflexes during imposed walking movements of the human ankle. Our overall objectives were to examine the role of peripheral afferents from the ankle in modulating stretch reflexes during imposed walking movements and to assess the mechanical consequences of this reflex activity. Specifically we sought to define the changes in the electromyographic (EMG) and mechanical responses to a stretch as a function of the phase of the step cycle. We recorded the ankle position of a normal subject walking on a treadmill at 3 km/h and used a hydraulic actuator to impose the same movements on supine subjects generating a constant level of ankle torque. Small pulse displacements, superimposed on the simulated walking movement, evoked stretch reflexes at different phases of the cycle. Three major findings resulted: 1) soleus reflex EMG responses were influenced strongly by imposed walking movements. The response amplitude was substantially smaller than that observed during steady-state conditions and was modulated throughout the step cycle. This modulation was qualitatively similar to that observed during active walking. Because central factors were held constant during the imposed walking experiments, we conclude that peripheral mechanisms were capable of both reducing the amplitude of the reflex EMG and producing its modulation throughout the movement. 2) Pulse disturbances applied from early to midstance of the imposed walking cycle generated large reflex torques, suggesting that the stretch reflex could help to resist unexpected perturbations during this phase of walking. In contrast, pulses applied during late stance and swing phase generated little reflex torque. 3) Reflex EMG and reflex torque were modulated differently throughout the imposed walking cycle. In fact, at the time when the reflex EMG response was largest, the corresponding reflex torque was negligible. Thus movement not only changes the reflex EMG but greatly modifies the mechanical output that results.
Voltage-Activated Potassium Outward Currents in Two Types of Spider Mechanoreceptor Neurons
Authors: Sekizawa Shin-Ichi , French Andrew S. , Höger Ulli , Torkkeli Päivi H.
Published: December 2017

Voltage-activated potassium outward currents in two types of spider mechanoreceptor neurons. We studied the properties of voltage-activated outward currents in two types of spider cuticular mechanoreceptor neurons to learn if these currents contribute to the differences in their adaptation properties. Both types of neurons adapt rapidly to sustained stimuli, but type A neurons usually only fire one or two action potentials, whereas type B neurons can fire bursts lasting several hundred milliseconds. We found that both neurons had two outward current components, 1) a transient current that activated rapidly when stimulated from resting potential and inactivated with maintained stimuli and 2) a noninactivating outward current. The transient outward current could be blocked by 5 mM tetraethylammonium chloride, 5 mM 4-aminopyridine, or 100 μM quinidine, but these blockers also reduced the amplitude of the noninactivating outward current. Charybdotoxin or apamin did not have any effect on the outward currents, indicating that Ca2+-activated K+ currents were not present or not inhibited by these toxins. The only significant differences between type A and type B neurons were found in the half-maximal activation ( V 50) values of both currents. The transient current had a V 50 value of 9.6 mV in type A neurons and −13.1 mV in type B neurons, whereas the V 50 values of noninactivating outward currents were −48.9 mV for type A neurons and −56.7 mV for type B neurons. We conclude that, although differences in the activation kinetics of the voltage-activated K+ currents could contribute to the difference in the adaptation behavior of type A and type B neurons, they are not major factors.
Response Attenuation During Coincident Afferent Excitatory Inputs
Authors: Kogo Naoki , Ariel Michael
Published: December 2017

Response attenuation during coincident afferent excitatory inputs. The linearity of the synaptic summation of two unitary excitatory synaptic events was investigated during whole cell recordings from retinal target neurons in an eye-attached isolated brain stem preparation. Pairs of unitary excitatory postsynaptic potentials (EPSPs) were evoked by bipolar stimulation electrodes that were directed to two distinct foci on the retinal surface based on the visual receptive field boundaries. The interval between stimulation of each retinal site was incremented by 0.5–1 ms to quantify the time course of nonlinear summation using an exponential fit. Response facilitation was never observed; however, the coincident arrival of synaptic inputs caused a response attenuation in 26 of the 37 pairs studied. Twelve of the 26 pairs had time constants of their attenuation that were similar to the time constants of the decaying phases of the first EPSPs of each pair. This suggests that the attenuation of these 12 pairs may be entirely due to voltage-dependent mechanisms, such as a reduction in driving force or a change of the activity of voltage-sensitive channels. On the other hand, the 14 other pairs had their time constant of attenuation shorter than the time constants of the decaying phase of the first EPSP. In fact, the attenuation time constants were often closer to the time constants of the decaying phases of the first excitatory postsynaptic currents of each pair. This finding suggests that the attenuation of these 14 pairs involve a shunting mechanism due to the opening of synaptic channels. The presence of this conductance-dependent mechanism is supported by the finding of asymmetric effects on the time course of attenuation when the stimulation sequence was reversed. These results are discussed in terms of the processing by neurons of coincident excitatory inputs onto spatially distinct points of their dendritic trees.
Parallel Activation of Primary and Secondary Somatosensory Cortices in Human Pain Processing
Authors: Ploner Markus , Schmitz Frank , Freund Hans-Joachim , Schnitzler Alfons
Published: December 2017

Parallel activation of primary and secondary somatosensory cortices in human pain processing. Cerebral processing of pain has been shown to involve primary (SI) and secondary (SII) somatosensory cortices. However, the temporal activation pattern of these cortices in nociceptive processing has not been demonstrated so far. We therefore used whole-head magnetoencephalography to record cortical responses to cutaneous laser stimuli in six healthy human subjects. By using selective nociceptive stimuli our results confirm involvement of contralateral SI and bilateral SII in human pain processing. Beyond they show for the first time simultaneous activation onset of contralateral SI and SII after ∼130 ms, indicating parallel thalamocortical distribution of nociceptive information. This contrasts to the serial cortical organization of tactile processing in higher primates and instead corresponds to the parallel cortical organization in lower primates and nonprimates. Thus our finding suggests preservation of the basic mammalian parallel organizational scheme in human pain processing, whereas in the tactile modality parallel organization appears to be abandoned in favor of a serial processing scheme. Functionally, preservation of direct access to SII underscores the relevance of this area in human pain processing, probably reflecting an important role of SII in nociceptive learning and memory.
TheDrosophilaNSF Protein, dNSF1, Plays a Similar Role at Neuromuscular and Some Central Synapses
Authors: Kawasaki Fumiko , Ordway Richard W.
Published: December 2017

The N-ethylmaleimide sensitive fusion protein (NSF) was originally identified as a cytosolic factor required for constitutive vesicular transport and later implicated in synaptic vesicle trafficking as well. Our previous work at neuromuscular synapses in the temperature-sensitive NSF mutant, comatose( comt), has shown that the comtgene product, dNSF1, functions after synaptic vesicle docking in the priming of vesicles for fast calcium-triggered fusion. Here we investigate whether dNSF1 performs a similar function at central synapses associated with the well-characterized giant fiber neural pathway. These include a synapse within the giant fiber pathway, made by the peripherally synapsing interneuron (PSI), as well as synapses providing input to the giant fiber pathway. The latency (delay) between stimulation and a resulting muscle action potential was used to assess the function of each class of synapses. Repetitive stimulation of the giant fiber pathway in comt produced wild-type responses at both 20 and 36°C, exhibiting a characteristic and constant latency between stimulation and the muscle response. In contrast, stimulation of presynaptic inputs to the giant fiber (referred to as the “long latency pathway”) revealed a striking difference between wild type and comt at 36°C. Repetitive stimulation of the long latency pathway led to a progressive, activity-dependent increase in the response latency in comt, but not in wild type. Thus the giant fiber pathway, including the PSI synapse, appears to function normally in comt, whereas the presynaptic inputs to the giant fiber pathway are disrupted. Several aspects of the progressive latency increase observed in the long latency pathway can be understood in the context of the activity-dependent reduction in neurotransmitter release we observed previously at neuromuscular synapses. These results suggest that repetitive stimulation causes a progressive reduction in neurotransmitter release by presynaptic inputs to the giant fiber neuron, resulting in an increased latency preceding a giant fiber action potential. Thus synapses presynaptic to the giant fiber appear to utilize dNSF1 in a manner similar to the neuromuscular synapse, whereas the PSI chemical synapse may differ with respect to the expression or activity of dNSF1.
Shape Interactions in Macaque Inferior Temporal Neurons
Authors: Missal Marcus , Vogels Rufin , Li Chao-Yi , Orban Guy A.
Published: December 2017

Missal et al. observed that the responses of inferior temporal (IT) neurons to a shape were reduced markedly when this shape partially overlapped a larger second shape, suggesting that shape interactions determine IT responses. In the present study, we compared the responses of IT neurons with combinations of two shapes which did or did not overlap and studied the effect of the relative and absolute positions of the two shapes. In a first test, a preferred shape (figure) was presented at the fixation point while a second, nonpreferred, shape was displayed either in the background of the figure (overlap) or at one of four peripheral positions (nonoverlap). Controls consisted of presentations of either shape in isolation at each of the five positions. The stimuli were presented during a fixation task. The responses to these combinations of two shapes were, on average, reduced compared with those elicited by the preferred shape presented in isolation. This suppression occurred whether or not the two shapes overlapped, but the degree of suppression in the overlap and nonoverlap conditions did not correlate. These interactions were stronger when the interacting stimulus was located in the contralateral compared with the ipsilateral hemifield. The position of the interacting stimulus within a hemifield significantly affected the suppression associated with combined shapes in some neurons. The strength of the interactions of the two nonoverlapping shapes depended on the shape of the interacting stimulus in half of the neurons. In a second test, the preferred shape and interacting stimulus could appear either at the fixation point or at one eccentric position. Here we found that the suppression was, on average, strongest when the interacting stimulus, rather than the preferred shape, was presented at the fixation position. Also, in 40% of the neurons, the response reduction was similar in overlap and nonoverlap conditions if effects of stimulus position were taken into account. In both tests, we also measured the responses to combinations of a nonpreferred shape and the interacting stimulus and showed that the response to a combination of two nonpreferred shapes was, in general, smaller than the response to a combination of the preferred and nonpreferred shape. Overall the results indicate that stimulus interactions in the receptive fields of IT neurons can be position and shape selective; this can contribute to the coding for the relationships between object parts.
Multimodal Medullary Neurons and Correlational Linkages of the Respiratory Network
Authors: Li Zhongzeng , Morris Kendall F. , Baekey David M. , Shannon Roger , Lindsey Bruce G.
Published: December 2017

This study addresses the hypothesis that multiple sensory systems, each capable of reflexly altering breathing, jointly influence neurons of the brain stem respiratory network. Carotid chemoreceptors, baroreceptors, and foot pad nociceptors were stimulated sequentially in 33 Dial-urethan–anesthetized or decerebrate vagotomized adult cats. Neuronal impulses were monitored with microelectrode arrays in the rostral and caudal ventral respiratory group (VRG), nucleus tractus solitarius (NTS), and n. raphe obscurus. Efferent phrenic nerve activity was recorded. Spike trains of 889 neurons were analyzed with cycle-triggered histograms and tested for respiratory-modulated firing rates. Responses to stimulus protocols were assessed with peristimulus time and cumulative sum histograms. Cross-correlation analysis was used to test for nonrandom temporal relationships between spike trains. Spike-triggered averages of efferent phrenic activity and antidromic stimulation methods provided evidence for functional associations of bulbar neurons with phrenic motoneurons. Spike train cross-correlograms were calculated for 6,471 pairs of neurons. Significant correlogram features were detected for 425 pairs, including 189 primary central peaks or troughs, 156 offset peaks or troughs, and 80 pairs with multiple peaks and troughs. The results provide evidence that correlational medullary assemblies include neurons with overlapping memberships in groups responsive to different sets of sensory modalities. The data suggest and support several hypotheses concerning cooperative relationships that modulate the respiratory motor pattern. 1) Neurons responsive to a single tested modality promote or limit changes in firing rate of multimodal target neurons. 2) Multimodal neurons contribute to changes in firing rate of neurons responsive to a single tested modality. 3) Multimodal neurons may promote responses during stimulation of one modality and “limit” changes in firing rates during stimulation of another sensory modality. 4) Caudal VRG inspiratory neurons have inhibitory connections that provide negative feedback regulation of inspiratory drive and phase duration.
Developmental Changes in Membrane Properties of Chemoreceptor Afferent Neurons of the Rat Petrosal Ganglia
Authors: Donnelly David F.
Published: December 2017

Carotid body chemoreceptors increase their responsiveness to hypoxia in the postnatal period, but the mechanism for this increase is unresolved. The purpose of the present study was to examine developmental changes in cellular characteristics of chemoreceptor afferent neurons in the petrosal ganglia with the underlying hypothesis that developmental changes occur and may account for the developmental increase in chemoreceptor responsiveness. Chemoreceptor complexes (carotid body, sinus nerve, glossopharyngeal nerve, and petrosal ganglia) were harvested from rats, aged 3–40 days, and intracellular recordings were obtained from petrosal ganglion neurons using sharp electrode impalement. All chemoreceptor neurons across ages were C fibers with conduction velocities <1 m/s and generated repetitive action potentials with depolarization. Resting membrane potential was −61.3 ± 0.9 (SE) mV ( n = 78) and input resistance was 108 ± 6 MΩ and did not significantly change with age. Cell capacitance was 32.4 ± 1.7 pF and did not change with age. Rheobase averaged 0.21 ± 0.02 nA and slightly increased with age. Action potentials were followed by an afterhyperpolarization of 12.4 ± 0.6 mV and time constant 6.9 ± 0.5 ms; only the time constant decreased with age. These results, obtained in rat, demonstrate electrophysiologic characteristics which differ substantially from that previously described in cat chemoreceptor neurons. In general developmental changes in cell characteristics are small and are unlikely to account for the developmental increase in chemoreceptor responsiveness with age.
Role of Metabotropic Glutamate Receptor Subtype mGluR1 in Brief Nociception and Central Sensitization of Primate STT Cells
Authors: Neugebauer Volker , Chen Ping-Sun , Willis William D.
Published: December 2017

G-protein coupled metabotropic glutamate receptors (mGluRs) are important modulators of synaptic transmission in the mammalian CNS and have been implicated in various forms of neuroplasticity and nervous system disorders. Increasing evidence also suggests an involvement of mGluRs in nociception and pain behavior although the contribution of individual mGluR subtypes is not yet clear. Subtypes mGluR1 and mGluR5 are classified as group I mGluRs and share the ability to stimulate phosphoinositide hydrolysis and activate protein kinase C. The present study examined the role of group I mGluRs in nociceptive processing and capsaicin-induced central sensitization of primate spinothalamic tract (STT) cells in vivo. In 10 anesthetized male monkeys ( Macaca fascicularis) extracellular recordings were made from 20 STT cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous stimuli of innocuous (BRUSH) and barely and substantially noxious (PRESS and PINCH, respectively) intensity were recorded before, during, and after the infusion of group I mGluR agonists and antagonists into the dorsal horn by microdialysis. Cumulative concentration–response relationships were obtained by applying different concentrations for at least 20 min each (at 5 μl/min). The actual concentrations reached in the tissue are 2–3 orders of magnitude lower than those in the microdialysis fibers (values in this paper refer to the latter). The group I antagonists were also applied at 10–25 min after capsaicin injection. S-DHPG, a group I agonist at both mGluR1 and mGluR5, potentiated the responses to innocuous and noxious stimuli (BRUSH > PRESS > PINCH) at low concentrations (10–100 μM; n = 5) but had inhibitory effects at higher concentrations (1–10 mM; n = 5). The mGluR5 agonist CHPG (1 μM-100 mM; n = 5) did not potentiate but inhibited all responses (10–100 mM; n = 5). AIDA (1 μM-100 mM), a mGluR1-selective antagonist, dose-dependently depressed the responses to PINCH and PRESS but not to BRUSH ( n = 6). The group I (mGluR1 > mGluR5) antagonist CPCCOEt (1 μM-100 mM) had similar effects ( n = 6). Intradermal injections of capsaicin sensitized the STT cells to cutaneous mechanical stimuli. The enhancement of the responses by capsaicin resembled the potentiation by the group I mGluR agonist S-DHPG (BRUSH > PRESS > PINCH). CPCCOEt (1 mM) reversed the capsaicin-induced sensitization when given as posttreatment ( n = 5). After washout of CPCCOEt, the sensitization resumed. Similarly, AIDA (1 mM; n = 7) reversed the capsaicin-induced sensitization and also blocked the potentiation by S-DHPG ( n = 5). These data suggest that the mGluR1 subtype is activated endogenously during brief high-intensity cutaneous stimuli (PRESS, PINCH) and is critically involved in capsaicin-induced central sensitization.
Hindlimb Locomotor and Postural Training Modulates Glycinergic Inhibition in the Spinal Cord of the Adult Spinal Cat
Authors: de Leon R. D. , Tamaki H. , Hodgson J. A. , Roy R. R. , Edgerton V. R.
Published: December 2017

Adult spinal cats were trained initially to perform either bipedal hindlimb locomotion on a treadmill or full-weight-bearing hindlimb standing. After 12 wk of training, stepping ability was tested before and after the administration (intraperitoneal) of the glycinergic receptor antagonist, strychnine. Spinal cats that were trained to stand after spinalization had poor locomotor ability as reported previously, but strychnine administration induced full-weight-bearing stepping in their hindlimbs within 30–45 min. In the cats that were trained to step after spinalization, full-weight-bearing stepping occurred and was unaffected by strychnine. Each cat then was retrained to perform the other task for 12 wk and locomotor ability was retested. The spinal cats that were trained initially to stand recovered the ability to step after they received 12 wk of treadmill training and strychnine was no longer effective in facilitating their locomotion. Locomotor ability declined in the spinal cats that were retrained to stand and strychnine restored the ability to step to the levels that were acquired after the step-training period. Based on analyses of hindlimb muscle electromyographic activity patterns and kinematic characteristics, strychnine improved the consistency of the stepping and enhanced the execution of hindlimb flexion during full-weight-bearing step cycles in the spinal cats when they were trained to stand but not when they were trained to step. The present findings provide evidence that 1) the neural circuits that generate full-weight-bearing hindlimb stepping are present in the spinal cord of chronic spinal cats that can and cannot step; however, the ability of these circuits to interpret sensory input to drive stepping is mediated at least in part by glycinergic inhibition; and 2) these spinal circuits adapt to the specific motor task imposed, and that these adaptations may include modifications in the glycinergic pathways that provide inhibition.
Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. I. Bursting Pacemaker Neurons
Authors: Butera Robert J. , Rinzel John , Smith Jeffrey C.
Published: December 2017

A network of oscillatory bursting neurons with excitatory coupling is hypothesized to define the primary kernel for respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC) in mammals. Two minimal models of these neurons are proposed. In model 1, bursting arises via fast activation and slow inactivation of a persistent Na+ current I NaP-h. In model 2, bursting arises via a fast-activating persistent Na+ current INaP and slow activation of a K+ current IKS. In both models, action potentials are generated via fast Na+ and K+currents. The two models have few differences in parameters to facilitate a rigorous comparison of the two different burst-generating mechanisms. Both models are consistent with many of the dynamic features of electrophysiological recordings from pre-BötC oscillatory bursting neurons in vitro, including voltage-dependent activity modes (silence, bursting, and beating), a voltage-dependent burst frequency that can vary from 0.05 to >1 Hz, and a decaying spike frequency during bursting. These results are robust and persist across a wide range of parameter values for both models. However, the dynamics of model 1 are more consistent with experimental data in that the burst duration decreases as the baseline membrane potential is depolarized and the model has a relatively flat membrane potential trajectory during the interburst interval. We propose several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.
Cannabinoid WIN 55,212-2 Inhibits the Activity-Dependent Facilitation of Spinal Nociceptive Responses
Authors: Strangman Nicole M. , Walker J. Michael
Published: December 2017

Cannabinoids suppress nociceptive processing of acute stimuli, but little is known about their effects on processes that lead to hyperexcitability of nociceptive neurons following prolonged noxious stimulation. Wind-up, the increasingly strong response of spinal nociceptive neurons to repetitive noxious electrical stimuli, results from a fast-rising cumulative depolarization and increase in intracellular calcium concentration. These processes produce central sensitization, the increased excitability of spinal nociceptive neurons that contributes to the hyperalgesia and allodynia associated with chronic pain. Intravenous injection of the potent, synthetic cannabinoid agonist WIN 55, 212-2, but not the inactive enantiomer, WIN 55,212-3, dose-dependently decreased the wind-up of spinal wide dynamic range and nociceptive-specific neurons independent of acute responses to activation of low- and high-threshold primary afferents. This is the first direct evidence that cannabinoids inhibit the activity-dependent facilitation of spinal nociceptive responses.
Dendrodendritic Recurrent Excitation in Mitral Cells of the Rat Olfactory Bulb
Authors: Aroniadou-Anderjaska Vassiliki , Ennis Matthew , Shipley Michael T.
Published: December 2017

Most neuronal interactions within the olfactory bulb network are mediated by dendrodendritic synapses. Dendritic transmitter release potentially could affect the parent dendrite as well as local neuronal elements that have receptors for the released transmitter. Here we report that under conditions that facilitate N-methyl-d-aspartate (NMDA) receptor activity (reduced GABAAinhibition and extracellular Mg2+), a single action potential evoked by brief intracellular current pulses in mitral cells is followed by a prolonged depolarization, which is blocked by an NMDA receptor antagonist. This depolarization also is evoked by a presumed calcium spike in the presence of tetrodotoxin. A similar NMDA-receptor-dependent prolonged depolarization is elicited by stimulation of the lateral olfactory tract at current intensities subthreshold for antidromic activation of the recorded neuron. These observations suggest that glutamate released from the dendrites of mitral cells excites the same and neighboring mitral cell dendrites. Further evidence suggests that both the apical and lateral dendrites of mitral cells participate in this recurrent excitation. These dendrodendritic interactions may play a role in the prolonged, NMDA-receptor-dependent depolarization of mitral/tufted cells evoked by olfactory nerve stimulation.
Differential Roles of Ionotropic Glutamate Receptors in Canine Medullary Inspiratory Neurons of the Ventral Respiratory Group
Authors: Krolo M. , Stuth E. A. , Tonkovic-Capin M. , Dogas Z. , Hopp F. A. , McCrimmon D. R. , Zuperku E. J.
Published: December 2017

The relative roles of ionotropic N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors in supplying excitatory drive to inspiratory (I) augmenting pattern neurons of the ventral respiratory group were studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microeject the NMDA antagonist, 2-amino-5-phosphonovalerate (AP5; 2 mM), the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( f)quinoxaline (NBQX; 0.25 mM), and an artificial cerebrospinal fluid vehicle. Ejected volume-rates were measured directly via meniscus level changes. The moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histograms of the discharge patterns. Both AP5 and NBQX produced dose-dependent reductions in peak spontaneous I neuronal discharge frequency ( F n). The average (± SE) maximum reduction in peak F n produced by AP5 was 69.1 ± 4.2% and by NBQX was 47.1 ± 3.3%. Blockade of both glutamate receptor subtypes nearly silenced these neurons, suggesting that their activity is highly dependent on excitatory synaptic drive mediated by ionotropic glutamate receptors. Differential effects were found for the two glutamatergic antagonists. AP5 produced downward, parallel shifts in the augmenting pattern of discharge, whereas NBQX reduced the slope of the augmenting discharge pattern. These results suggest that time-varying excitatory input patterns to the canine I bulbospinal neurons are mediated by non-NMDA glutamate receptors and that constant or tonic input patterns to these neurons are mediated by NMDA receptors.
GABABReceptor-Mediated Regulation of Glutamate-Activated Calcium Transients in Hypothalamic and Cortical Neuron Development
Authors: Obrietan Karl , van den Pol Anthony
Published: December 2017

In the mature nervous system excitatory neurotransmission mediated by glutamate is balanced by the inhibitory actions of GABA. However, during early development, GABA acting at the ligand-gated GABAACl−channel also exerts excitatory actions. This raises a question as to whether GABA can exert inhibitory activity during early development, possibly by a mechanism that involves activation of the G protein-coupled GABABreceptor. To address this question we used Ca2+digital imaging to assess the modulatory role of GABABreceptor signaling in relation to the excitatory effects of glutamate during hypothalamic and cortical neuron development. Ca2+transients mediated by synaptic glutamate release in neurons cultured from embryonic rat were dramatically depressed by the administration of the GABABreceptor agonist baclofen in a dose-dependent manner. The inhibitory effects of GABABreceptor activation persisted for the duration of baclofen administration (>10 min). Preincubation with the Gi protein inhibitor pertussis toxin resulted in a substantial decrease in the inhibitory actions of baclofen, confirming that a Gi-dependent mechanism mediated the effects of the GABABreceptor. Co-administration of the GABABreceptor antagonist 2-hydroxy-saclofen eliminated the inhibitory action of baclofen. Alone, GABABantagonist application elicited a marked potentiation of Ca2+transients mediated by glutamatergic neurotransmission, suggesting that tonic synaptic GABA release exerts an inhibitory tone on glutamate receptor-mediated Ca2+transients via GABABreceptor activation. In the presence of TTX to block action potential-mediated neurotransmitter release, stimulation with exogenously applied glutamate triggered a robust postsynaptic Ca2+rise that was dramatically depressed (>70% in cortical neurons, >40% in hypothalamic neurons) by baclofen. Together these data suggest both a pre- and postsynaptic component for the modulatory actions of the GABABreceptor. These results indicate a potentially important role for the GABABreceptor as a modulator of the excitatory actions of glutamate in developing neurons.
N-Methyl-d-Aspartate–Induced Oscillations in Whole Cell Clamped Neurons From the Isolated Spinal Cord ofXenopus laevisEmbryos
Authors: Prime L. , Pichon Y. , Moore L. E.
Published: December 2017

The patch-clamp technique was used to measure the effect of N-methyl-d-aspartate (NMDA) on Xenopus embryonic neurons in an isolated, but intact spinal cord. Whole cell recordings were done at external calcium concentrations of 1 mM. NMDA alone (50–200 μM) or in association with 10 μM serotonin or glycine induced oscillatory activity in most presumed motoneurons, which were therefore considered part of rhythm generating networks. In the presence of TTX, one-half of these neurons maintained this activity. The oscillations fell into two main categories: voltage-dependent, low-frequency (0.3–0.5 Hz) and voltage-independent, high-frequency (3–8 Hz) oscillations. NMDA alone induced TTX-insensitive oscillations in one-third of the neurons; however, the percentage of neurons showing oscillations was greater in the presence of exogenous 5-hydroxytryptamine (5-HT) or glycine. Because these observations were made at embryonic stages where little or no serotonergic innervation exists, it is likely that NMDA-induced intrinsic oscillatory activity in Xenopus embryonic neurons does not require 5-HT.