bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Role of KIR Channel and Na+/K+-Pump in the Regulation of Extracellular K+ in Rat Hippocampus
Authors: D'Ambrosio Raimondo , Gordon David S. , Winn H. Richard
Published: May 2017

Little information is available on the specific roles of different cellular mechanisms involved in extracellular K+ homeostasis during neuronal activity in situ. These studies have been hampered by the lack of an adequate experimental paradigm able to separate K+-buffering activity from the superimposed extrusion of K+ from variably active neurons. We have devised a new protocol that allows for such an analysis. We used paired field- and K+-selective microelectrode recordings from CA3 stratum pyramidale during maximal Schaffer collateral stimulation in the presence of excitatory synapse blockade to evoke purely antidromic spikes in CA3. Under these conditions of controlled neuronal firing, we studied the [K+]o baseline during 0.05 Hz stimulation, and the accumulation and rate of recovery of extracellular K+ at higher frequency stimulation (1–3 Hz). In the first set of experiments, we showed that neuronal hyperpolarization by extracellular application of ZD7288 (11 μM), a selective blocker of neuronal I hcurrents, does not affect the dynamics of extracellular K+. This indicates that the K+ dynamics evoked by controlled pyramidal cell firing do not depend on neuronal membrane potential, but only on the balance between K+ extruded by firing neurons and K+ buffered by neuronal and glial mechanisms. In the second set of experiments, we showed that di-hydro-ouabain (5 μM), a selective blocker of the Na+/K+-pump, yields an elevation of baseline [K+]o and abolishes the K+ recovery during higher frequency stimulation and its undershoot during the ensuing period. In the third set of experiments, we showed that Ba2+ (200 μM), a selective blocker of inwardly rectifying K+channels (KIR), does not affect the posttetanus rate of recovery of [K+]o, nor does it affect the rate of K+ recovery during high-frequency stimulation. It does, however, cause an elevation of baseline [K+]o and an increase in the amplitude of the ensuing undershoot. We show for the first time that it is possible to differentiate the specific roles of Na+/K+-pump and KIR channels in buffering extracellular K+. Neuronal and glial Na+/K+-pumps are involved in setting baseline [K+]o levels, determining the rate of its recovery during sustained high-frequency firing, and determining its postactivity undershoot. Conversely, glial KIR channels are involved in the regulation of baseline levels of K+, and in decreasing the amplitude of the postactivity [K+]oundershoot, but do not affect the rate of K+clearance during neuronal firing. The results presented provide new insights into the specific physiological role of glial KIR channels in extracellular K+ homeostasis.
Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks
Authors: Takeda Kazuyoshi , Funahashi Shintaro
Published: May 2017

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.
Fine Temporal Resolution of Analytic Phase Reveals Episodic Synchronization by State Transitions in Gamma EEGs
Authors: Freeman Walter J. , Rogers Linda J.
Published: May 2017

The analytic signal given by the Hilbert transform applied to an electroencephalographic (EEG) trace is a vector of instantaneous amplitude and phase at the temporal resolution of the digitizing interval (here 2 ms). The transform was applied after band-pass filtering for extracting the gamma band (20–80 Hz in rabbits) to time series from up to 64 EEG channels recorded simultaneously from high-density arrays giving spatial “windows” of 4 × 4 to 6 × 6 mm onto the visual, auditory, or somatosensory cortical surface. The time series of the analytic phase revealed phase locking for brief time segments in spatial patterns of nonzero phase values from multiple EEG that was punctuated by episodic phase decoherence. The derivative of the analytic phase revealed spikes occurring not quite simultaneously (within ±4 ms) across arrays aperiodically at mean rates in and below the theta range (3–7 Hz). Two measures of global synchronization over a group of channels were derived from analytic phase differences between pairs of channels on the same area of cortex. One was a synchronization index expressing phase locking. The other was a decoherence index estimating the variance in phase among multiple channels. Spectral analyses of the indices indicated that decoherence events recurred aperiodically at rates in and below the theta range of the EEGs. The results provide support for the hypothesis that neurons in mesoscopic neighborhoods in sensory cortices self-organize their activity by synaptic interactions into wave packets that have spatial patterns of amplitude (AM) and phase (PM) modulation of their spatially coherent carrier waves in the gamma range and that form and dissolve aperiodically at rates in and below the theta range. Each AM pattern is formed by a nonlinear state transition in the cortical dynamics, as shown by spikes in the derivative. Phase locking within each PM pattern is not at zero phase lag but over a fixed distribution of phase values that is consistent with the radially symmetric phase gradients already reported called “phase cones” detected by Fourier-based methods. The insight is suggested that sensory cortices are bistable comparably to cardiac dynamics, with a diastolic state that accepts sensory input and an abrupt transition to a systolic state that transmits perceptual output. Further support for this inference will require improvements in methods for temporal resolution of the times of onset of spatial patterns of phase modulation.
Hippocampal Astrocytes In Situ Exhibit Calcium Oscillations That Occur Independent of Neuronal Activity
Authors: Nett Wolfgang J. , Oloff Scott H. , McCarthy Ken D.
Published: May 2017

Results presented in this study indicate that a large subpopulation (∼65%) of hippocampal astrocytes in situ exhibit calcium oscillations in the absence of neuronal activity. Further, the spontaneous oscillations observed within individual hippocampal astrocytes generally developed asynchronously throughout the astrocyte's fine processes and occasionally spread through a portion of that astrocyte as a calcium wave but do not appear to spread among astrocytes as an intercellular calcium wave. Bath application of cyclopiazonic acid and injection of individual astrocytes with heparin blocked astrocytic calcium oscillations. Application of tetrodotoxin or incubation of slices with bafilomycin A1 had no effect on astrocytic calcium oscillations but did block evoked and spontaneous postsynaptic currents measured in CA1 pyramidal neurons. Application of a cocktail of antagonists for metabotropic glutamate receptors and purinergic receptors had no effect on the astrocytic calcium oscillations but blocked the ability of purinergic and metabotropic glutamatergic agonists to increase astrocytic calcium levels. These results indicate that the spontaneous calcium oscillations observed in hippocampal astrocytes in situ are mediated by IP3receptor activation, are not dependent on neuronal activity, and do not depend on activation of metabotropic glutamate receptors or purinergic receptors. To our knowledge, this is the first demonstration that astrocytes in situ exhibit intrinsic signaling. This finding supports the hypothesis that astrocytes, independent of neuronal input, may act as pacemakers to modulate neuronal activity in situ.
Adaptive Changes in Early and Late Blind: A fMRI Study of Braille Reading
Authors: Burton H. , Snyder A. Z. , Conturo T. E. , Akbudak E. , Ollinger J. M. , Raichle M. E.
Published: May 2017

Braille reading depends on remarkable adaptations that connect the somatosensory system to language. We hypothesized that the pattern of cortical activations in blind individuals reading Braille would reflect these adaptations. Activations in visual (occipital-temporal), frontal-language, and somatosensory cortex in blind individuals reading Braille were examined for evidence of differences relative to previously reported studies of sighted subjects reading print or receiving tactile stimulation. Nine congenitally blind and seven late-onset blind subjects were studied with fMRI as they covertly performed verb generation in response to reading Braille embossed nouns. The control task was reading the nonlexical Braille string “######”. This study emphasized image analysis in individual subjects rather than pooled data. Group differences were examined by comparing magnitudes and spatial extent of activated regions first determined to be significant using the general linear model. The major adaptive change was robust activation of visual cortex despite the complete absence of vision in all subjects. This included foci in peri-calcarine, lingual, cuneus and fusiform cortex, and in the lateral and superior occipital gyri encompassing primary (V1), secondary (V2), and higher tier (VP, V4v, LO and possibly V3A) visual areas previously identified in sighted subjects. Subjects who never had vision differed from late blind subjects in showing even greater activity in occipital-temporal cortex, provisionally corresponding to V5/MT and V8. In addition, the early blind had stronger activation of occipital cortex located contralateral to the hand used for reading Braille. Responses in frontal and parietal cortex were nearly identical in both subject groups. There was no evidence of modifications in frontal cortex language areas (inferior frontal gyrus and dorsolateral prefrontal cortex). Surprisingly, there was also no evidence of an adaptive expansion of the somatosensory or primary motor cortex dedicated to the Braille reading finger(s). Lack of evidence for an expected enlargement of the somatosensory representation may have resulted from balanced tactile stimulation and gross motor demands during Braille reading of nouns and the control fields. Extensive engagement of visual cortex without vision is discussed in reference to the special demands of Braille reading. It is argued that these responses may represent critical language processing mechanisms normally present in visual cortex.
Jittery Trains Induced by Synaptic-Like Currents in Cerebellar Inhibitory Interneurons
Authors: Mann-Metzer Puah , Yarom Yosef
Published: May 2017

Cerebellar inhibitory interneurons respond to parallel fiber input with a characteristic train of action potentials. Here we show that the characteristics of these trains reflect the intrinsic properties of the interneurons. In in vitro cerebellar slices, the response of these neurons to synaptic-like current resembles their in vivo response to parallel fiber input—a train of action potentials characterized by a gradual increase in interspike interval and spike amplitude. A large variability in spike timing, or jitter, was observed, the last action potential emerging from a slow depolarizing wave that lasted beyond the synaptic current and was prevented by either TTX or membrane hyperpolarization. While response duration was weakly dependent on current intensity, the variability of the overall duration was closely related to the variability of the timing of the last action potential. Blocking the Ca2+ currents or partial blockade of the delayed rectifier (TEA 2 mM) decreased the excitability, leading to a decrease in the duration and variability of the response and increasing its dependence on stimulus intensity. Increased duration and variability was observed in the presence of Cs+ ions (5 mM) that blocked an h-like current. We conclude that a persistent Na+ current governs the duration of the response, whereas the synaptic current and the spiking mechanism shape its pattern. The large variability between trials is due to the stochastic nature of the persistent Na+ current. Thus unless precise timing is achieved by a network of interconnected neurons, these results vote against temporal coding as a player in the cerebellar computational processing.
Comparison of Cortico-Cortical and Cortico-Collicular Signals for the Generation of Saccadic Eye Movements
Authors: Ferraina Stefano , Paré Martin , Wurtz Robert H.
Published: May 2017

Many neurons in the frontal eye field (FEF) and lateral intraparietal (LIP) areas of cerebral cortex are active during the visual-motor events preceding the initiation of saccadic eye movements: they respond to visual targets, increase their activity before saccades, and maintain their activity during intervening delay periods. Previous experiments have shown that the output neurons from both LIP and FEF convey the full range of these activities to the superior colliculus (SC) in the brain stem. These areas of cerebral cortex also have strong interconnections, but what signals they convey remains unknown. To determine what these cortico-cortical signals are, we identified the LIP neurons that project to FEF by antidromic activation, and we studied their activity during a delayed-saccade task. We then compared these cortico-cortical signals to those sent subcortically by also identifying the LIP neurons that project to the intermediate layers of the SC. Of 329 FEF projection neurons and 120 SC projection neurons, none were co-activated by both FEF and SC stimulation. FEF projection neurons were encountered more superficially in LIP than SC projection neurons, which is consistent with the anatomical projection of many cortical layer III neurons to other cortical areas and of layer V neurons to subcortical structures. The estimated conduction velocities of FEF projection neurons (16.7 m/s) were significantly slower that those of SC projection neurons (21.7 m/s), indicating that FEF projection neurons have smaller axons. We identified three main differences in the discharge properties of FEF and SC projection neurons: only 44% of the FEF projection neurons changed their activity during the delayed-saccade task compared with 69% of the SC projection neurons; only 17% of the task-related FEF projection neurons showed saccadic activity, whereas 42% of the SC projection neurons showed such increases; 78% of the FEF projection neurons had a visual response but no saccadic activity, whereas only 55% of the SC projection neurons had similar activity. The FEF and SC projection neurons had three similarities: both had visual, delay, and saccadic activity, both had stronger delay and saccadic activity with visually guided than with memory-guided saccades, and both had broadly tuned responses for disparity stimuli, suggesting that their visual receptive fields have a three-dimensional configuration. These observations indicate that the activity carried between parietal and frontal cortical areas conveys a spectrum of signals but that the preponderance of activity conveyed might be more closely related to earlier visual processing than to the later saccadic stages that are directed to the SC.
Role of Inhibition for Temporal and Spatial Odor Representation in Olfactory Output Neurons: A Calcium Imaging Study
Authors: Sachse Silke , Galizia C. Giovanni
Published: May 2017

The primary olfactory brain center, the antennal lobe (AL) in insects or the olfactory bulb in vertebrates, is a notable example of a neural network for sensory processing. While physiological properties of the input, the olfactory receptor neurons, have become clearer, the operation of the network itself remains cryptic. Therefore we measured spatio-temporal odor-response patterns in the output neurons of the olfactory glomeruli using optical imaging in the honeybee Apis mellifera. We mapped these responses to identified glomeruli, which are the structural and functional units of the AL. Each odor evoked a complex spatio-temporal activity pattern of excited and inhibited glomeruli. These properties were odor- and glomerulus-specific and were conserved across individuals. We compared the spatial pattern of excited glomeruli to previously published signals, which derived mainly from the receptor neurons, and found that they appeared more confined, showing that inhibitory connections enhance the contrast between glomeruli in the AL. To investigate the underlying mechanisms, we applied GABA and the GABA-receptor antagonist picrotoxin (PTX). The results show the presence of two separate inhibitory networks: one is GABAergic and modulates overall AL activity, the other is PTX-insensitive and glomerulus-specific. Inhibitory connections of the latter network selectively inhibit glomeruli with overlapping response profiles, in a way akin to “lateral” inhibition in other sensory systems. Selectively inhibited glomeruli need not be spatial neighbors. The net result is a globally modulated, contrast-enhanced and predictable representation of odors in the olfactory output neurons.
Model of Intersegmental Coordination in the Leech Heartbeat Neuronal Network
Authors: Hill Andrew A. V. , Masino Mark A. , Calabrese Ronald L.
Published: May 2017

We have created a computational model of the timing network that paces the heartbeat of the medicinal leech, Hirudo medicinalis. The rhythmic activity of this network originates from two segmental oscillators located in the third and fourth midbody ganglia. In the intact nerve cord, these segmental oscillators are mutually entrained to the same cycle period. Although experiments have shown that the segmental oscillators are coupled by inhibitory coordinating interneurons, the underlying mechanisms of intersegmental coordination have not yet been elucidated. To help understand this coordination, we have created a simple computational model with two variants: symmetric and asymmetric. In the symmetric model, neurons within each segmental oscillator called oscillator interneurons, inhibit the coordinating interneurons. In contrast, in the asymmetric model only the oscillator interneurons of one segmental oscillator inhibit the coordinating interneurons. In the symmetric model, when two segmental oscillators with different inherent periods are coupled, the faster one leads in phase, and the period of the coupled system is equal to the period of the faster oscillator. This behavior arises because, during each oscillation cycle, the oscillator interneurons of the faster segmental oscillator begin to burst before those of the slower oscillator, thereby terminating spike activity in the coordinating interneurons. Thus there is a brief period of time in each cycle when the oscillator interneurons of the slower segmental oscillator are relieved of inhibition from the coordinating interneurons. This “removal of synaptic inhibition” allows, within certain limits, the slower segmental oscillator to be sped to the period of the faster one. Thus the symmetric model demonstrates a plausible biophysical mechanism by which one segmental oscillator can entrain the other. In general the asymmetric model, in which only one segmental oscillator has the ability to inhibit the coordinating interneurons, behaves similarly, except only one segmental oscillator can control the period of the system. In addition, we simulated physiological experiments in which a “driving” stimulus, consisting of alternating positive and negative current steps, was used to control a single oscillator interneuron and thereby entrain the activity of the entire timing network.
Pre- and Postsynaptic Inhibition Mediated by GABABReceptors in Cerebellar Inhibitory Interneurons
Authors: Mann-Metzer Puah , Yarom Yosef
Published: May 2017

The inhibitory interneurons in the molecular layer of the cerebellar cortex form a complex network, interconnected by both chemical and electrotonic synapses. Previous work, using voltage optical imaging in an isolated cerebellum, has indicated that these interneurons also form presynaptic inhibitory interconnections. Here we examine the participation of GABABreceptors in the proposed presynaptic inhibition by recording from the molecular layer interneurons (MLI) in cerebellar slices. The GABAB agonist, baclofen, profoundly depressed synaptic transmission; a concentration of 10 μM decreased the frequency of spontaneous inhibitory synaptic potentials by 82 ± 15% and of miniature synaptic potentials by 75 ± 13%. In simultaneous recording from two synaptically interconnected MLIs, baclofen (10 μM) increased the failure rate of synaptic transmission by a factor of 3, confirming a presynaptic mechanism, most likely mediated by a decrease in calcium conductance. A postsynaptic effect of baclofen was also found; 10 μM decreased the spontaneous firing rate by 55 ± 19% even in the presence of synaptic blockers. One hundred micromolar baclofen induced an averaged hyperpolarization of 6 ± 2 mV or an averaged 7.8 ± 3 pA net outward current that can account for the decrease in firing rate. The outward current reflects a reduction in a tonic Ca2+ current, since it was abolished by blocking Ca2+ currents and remained unchanged in the presence of Ba2+. Application of the specific GABAB blocker, CGP 55845A (1 μM), not only reversed the effects of baclofen but also increased the spontaneous firing rate and synaptic activity when applied alone. Thus in slice preparations, GABABreceptors are tonically activated by endogenous GABA. The temporal role of GABAB receptors was tested using the paired-pulse paradigm. Recording from two synaptically interconnected MLIs showed a 3.5 times lower probability of release for the second stimulus. In the isolated cerebellar preparation, a robust depression of the second inhibitory response was observed. This depression was partially blocked by CGP 55845A (2 μM). We conclude that both the pre- and postsynaptic effects of baclofen are mediated by GABAB receptors that decrease Ca2+ currents. These can serve a modulatory role as well as participating in shaping the temporal interactions between consecutive inputs.
Limbic Network Interactions Leading to Hyperexcitability in a Model of Temporal Lobe Epilepsy
Authors: D'Antuono Margherita , Benini Ruba , Biagini Giuseppe , D'Arcangelo Giovanna , Barbarosie Michaela , Tancredi Virginia , Avoli Massimo
Published: May 2017

In mouse brain slices that contain reciprocally connected hippocampus and entorhinal cortex (EC) networks, CA3 outputs control the EC propensity to generate experimentally induced ictal-like discharges resembling electrographic seizures. Neuronal damage in limbic areas, such as CA3 and dentate hilus, occurs in patients with temporal lobe epilepsy and in animal models (e.g., pilocarpine- or kainate-treated rodents) mimicking this epileptic disorder. Hence, hippocampal damage in epileptic mice may lead to decreased CA3 output function that in turn would allow EC networks to generate ictal-like events. Here we tested this hypothesis and found that CA3-driven interictal discharges induced by 4-aminopyridine (4AP, 50 μM) in hippocampus-EC slices from mice injected with pilocarpine 13–22 days earlier have a lower frequency than in age-matched control slices. Moreover, EC-driven ictal-like discharges in pilocarpine-treated slices occur throughout the experiment (≤6 h) and spread to the CA1/subicular area via the temporoammonic path; in contrast, they disappear in control slices within 2 h of 4AP application and propagate via the trisynaptic hippocampal circuit. Thus, different network interactions within the hippocampus-EC loop characterize control and pilocarpine-treated slices maintained in vitro. We propose that these functional changes, which are presumably caused by seizure-induced cell damage, lead to seizures in vivo. This process is facilitated by a decreased control of EC excitability by hippocampal outputs and possibly sustained by the reverberant activity between EC and CA1/subiculum networks that are excited via the temporoammonic path.
Nitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation
Authors: Renganathan M. , Cummins T. R. , Waxman S. G.
Published: May 2017

C-type dorsal root ganglion (DRG) neurons express three types of Na+ currents: fast TTX-sensitive, slow TTX-resistant, and persistent TTX-resistant Na+ currents. The nitric oxide (NO) donors papa-NONOate and S-nitroso- N-acetyl-dl-penicillamine inhibit all three types of Na+ currents. The NO scavenger hemoglobin abolished the effects of papa-NONOate on Na+ currents, indicating that NO or NO-related species inhibit these Na+ currents. NO donor inhibition of all three types of Na+ currents was reversed by washout. Incubation of neurons with 8-bromo cGMP, a membrane-permeable analogue of cGMP, and cG-PKI, an inhibitor of cGMP-dependent protein kinase, had no effect on papa-NONOate-mediated Na+ current block, demonstrating that Na+ current inhibition is independent of cGMP. Alkylation of free thiols with N-ethylmaleimide prevented the actions of papa-NONOate, suggesting that NO, or a related reactive nitrogen species, modifies sulfhydryl groups on Na+ channels or a closely associated protein. Papa-NONOate-mediated block of Na+ currents is not due to a hyperpolarizing shift in steady state voltage-dependent inactivation. The absence of NO-mediated enhancement of slow inactivation in fast and slow Na+ channels indicates that NO does not inhibit fast and slow Na+ channels by facilitating the transition to a slow inactivated state. These results demonstrate that inhibition of Na+ currents is not due to the modulation of fast and slow sodium channel inactivation. Taken together, these results show that NO or NO-related products modify the sulfhydryl groups on Na+ channels and inhibit Na+ currents by blocking the channel conductance.
Spectrotemporal Receptive Fields in the Lemniscal Auditory Thalamus and Cortex
Authors: Miller Lee M. , Escabí Monty A. , Read Heather L. , Schreiner Christoph E.
Published: May 2017

Receptive fields have been characterized independently in the lemniscal auditory thalamus and cortex, usually with spectrotemporally simple sounds tailored to a specific task. No studies have employed naturalistic stimuli to investigate the thalamocortical transformation in temporal, spectral, and aural domains simultaneously and under identical conditions. We recorded simultaneously in the ventral division of the medial geniculate body (MGBv) and in primary auditory cortex (AI) of the ketamine-anesthetized cat. Spectrotemporal receptive fields (STRFs) of single units ( n = 387) were derived by reverse-correlation with a broadband and dynamically varying stimulus, the dynamic ripple. Spectral integration, as measured by excitatory bandwidth and spectral modulation preference, was similar across both stations (mean Q1/e thalamus = 5.8, cortex = 5.4; upper cutoff of spectral modulation transfer function, thalamus = 1.30 cycles/octave, cortex = 1.37 cycles/octave). Temporal modulation rates slowed by a factor of two from thalamus to cortex (mean preferred rate, thalamus = 32.4 Hz, cortex = 16.6 Hz; upper cutoff of temporal modulation transfer function, thalamus = 62.9 Hz, cortex = 37.4 Hz). We found no correlation between spectral and temporal integration properties, suggesting that the excitatory-inhibitory interactions underlying preference in each domain are largely independent. A small number of neurons in each station had highly asymmetric STRFs, evidence of frequency sweep selectivity, but the population showed no directional bias. Binaural preferences differed in their relative proportions, most notably an increased prevalence of excitatory contralateral-only cells in cortex (40%) versus thalamus (23%), indicating a reorganization of this parameter. By comparing simultaneously along multiple stimulus dimensions in both stations, these observations establish the global characteristics of the thalamocortical receptive field transformation.
Adaptive Changes in Locomotor Activity Following Botulinum Toxin Injection in Ankle Extensor Muscles of Cats
Authors: Misiaszek J. E. , Pearson K. G.
Published: May 2017

The present study investigated the adaptations made in motor behavior following a temporary reduction in ankle extensor activity in the walking cat. Temporary muscle weakness was induced by injecting botulinum toxin into the lateral gastrocnemius (LG), plantaris (PL), and soleus (SOL) muscles, or SOL alone. The medial gastrocnemius (MG) muscle was not injected. Adaptations in the level of muscle activity were recorded using chronically implanted electromyographic (EMG) electrodes. Serial recordings were made prior to botulinum toxin injections and for several days following the injections. Kinematic analysis of ankle joint movements was made from video records to assess the impact of the botulinum toxin injections on the function of the ankle joint during walking. Following injection of the LG, PL, and SOL muscles with botulinum toxin, the amplitude of the MG burst increased over a period of a few days to a week. This increase was similar to the previously reported changes produced in MG following transection of the nerves serving LG, PL, and SOL. Following the weakening of the ankle extensor muscles, there was a temporary deficit in ankle function during walking as evidenced by a marked increase in the amount of ankle flexion that occurred at stance onset. This functional deficit recovered relatively quickly and was not associated with a return of the EMG pattern to the preinjection pattern. After recovery from the initial injections, a second injection of botulinum toxin into SOL alone was performed. No functional deficits were observed in the ankle movements during walking following this second injection. However, weakening SOL produced increases in the burst amplitudes of the MG, LG, and PL muscles over a period of a few days. This suggests that normal movements at the ankle during walking can be generated with more than one pattern of ankle extensor activity and that there is flexibility in how the necessary torque is produced. A final procedure, transection of the nerves serving LG, PL, and SOL, failed to produce any functional deficits in ankle movements. The implication is that adaptations to the neural control of ankle extensor activity that were induced by the initial procedure persisted after the recovery of the injected muscles and were sufficient to compensate for the subsequent challenges.
Failure of Averaging in the Construction of a Conductance-Based Neuron Model
Authors: Golowasch Jorge , Goldman Mark S. , Abbott L. F. , Marder Eve
Published: May 2017

Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.
Synergistic Enhancement of Glutamate-Mediated Responses by Serotonin and Forskolin in Adult Mouse Spinal Dorsal Horn Neurons
Authors: Wang Guo-Du , Zhuo Min
Published: May 2017

Glutamate is the major excitatory amino acid neurotransmitter in the CNS, including the neocortex, hippocampus, and spinal cord. Normal synaptic transmission is mainly mediated by glutamate AMPA and/or kainate receptors. Glutamate N-methyl-d-aspartate (NMDA) receptors are normally inactive and only activated when a sufficient postsynaptic depolarization is induced by the activity. Here we show that in sensory synapses of adult mouse, some synaptic responses (26.3% of a total of 38 experiments) between primary afferent fibers and dorsal horn neurons are almost completely mediated by NMDA receptors. Dorsal root stimulation did not elicit any detectable AMPA/kainate receptor-mediated responses in these synapses. Unlike young spinal cord, serotonin alone did not produce any long-lasting synaptic enhancement in adult spinal dorsal horn neurons. However, co-application of the adenylyl cyclase activator forskolin and serotonin (5-HT) produced long-lasting enhancement, including the recruitment of functional AMPA receptor-mediated responses. Calcium-sensitive, calmodulin-regulated adenylyl cyclases (AC1, AC8) are required for the enhancement. Furthermore the thresholds for generating action potential responses were decreased, and, in many cases, co-application of forskolin and 5-HT led to the generation of action potentials by previously subthreshold stimulation of primary afferent fibers in the presence of the NMDA receptor blocker 2-amino-5-phosphonovaleric acid. Our results suggest that pure NMDA synapses exist on sensory neurons in adult spinal cord and that they may contribute to functional sensory transmission. The synergistic recruitment of functional AMPA responses by 5-HT and forskolin provides a new cellular mechanism for glutamatergic synapses in mammalian spinal cord.
Slow Oscillatory Discharge in the Primate Basal Ganglia
Authors: Wichmann Thomas , Kliem Michele A. , Soares Jesus
Published: May 2017

Oscillations with periods in the multisecond range have previously been recorded in basal ganglia neurons of awake paralyzed rats, and in these animals were shown to be increased by systemic dopaminergic stimulation, but not altered by depletion of the nigrostriatal dopamine supply. To determine whether oscillations with frequencies below 0.5 Hz also exist in the primate basal ganglia, the spontaneous neuronal activity in the subthalamic nucleus (STN) and in the external and internal segments of the globus pallidus (GPe and GPi, respectively) was recorded with standard extracellular recording methods in two animals before and after treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Oscillations with mean periods around 80 s were identified in 30% percent of GPe neurons, 36% of STN neurons, and 48% of GPi neurons. After recording in the normal state, the animals were rendered parkinsonian by intracarotid application of MPTP. This treatment resulted in a 30% reduction of the average discharge rate in GPe, a 47% increase of the average discharge rate in STN, and a 15% increase of the average discharge rate in GPi. However, there were no changes in the proportion of cells with slow oscillatory discharge. The oscillation frequencies were slightly increased in STN but remained unchanged in GPe and GPi. The results demonstrate that multisecond oscillations commonly occur in primate basal ganglia neurons and are unchanged by treatment with MPTP. The oscillations may have roles in fundamental functions of the basal ganglia-thalamocortical network, such as the regulation of the state of arousal.
Interneuronal and Peptidergic Control of Motor Pattern Switching inAplysia
Authors: Morgan Peter T. , Jing Jian , Vilim Ferdinand S. , Weiss Klaudiusz R.
Published: May 2017

It has been proposed that a choice of specific behaviors can be mediated either by activation of behavior-specific higher order neurons or by distinct combinations of such neurons in different behaviors. We examined the role that two higher order neurons, CBI-2 and CBI-3, play in the selection of motor programs that correspond to ingestion and egestion, two stimulus-dependent behaviors that are generated by a single central pattern generator (CPG) of Aplysia. We found that CBI-2 could evoke either ingestive, egestive, or ambiguous motor programs depending on the regime of stimulation. When CBI-2 recruited CBI-3 firing via electrical coupling, the motor program tended to be ingestive. In the absence of CBI-3 activation, the program was usually egestive. When CBI-2 was stimulated to produce ingestive programs, hyperpolarization of CBI-3 converted the programs to egestive or ambiguous. When CBI-2 was stimulated to produce egestive or ambiguous programs, co-stimulation of CBI-3 converted them into ingestive. These findings are consistent with the idea that combinatorial commands are responsible for the choice of specific behaviors. Additional support for this view comes from the observations that appropriate stimulus conditions exist both for activation of CBI-2 together with CBI-3, and for activation of CBI-2 without a concomitant activation of CBI-3. The ability of CBI-3 to convert egestive and ambiguous programs into ingestive ones was mimicked by application of APGWamide, a neuropeptide that we have detected in CBI-3 by immunostaining. Thus combinatorial actions of higher order neurons that underlie pattern selection may involve the use of modulators released by specific higher order neurons.
Podokinetic After-Rotation Following Unilateral and Bilateral Podokinetic Stimulation
Authors: Earhart Gammon M. , Jones G. Melvill , Horak F. B. , Block E. W. , Weber K. D. , Fletcher W. A.
Published: May 2017

Previous studies demonstrated an aftereffect of walking on a rotating treadmill, involving inadvertent circular navigation with eyes closed [podokinetic after-rotation (PKAR)]. We compared PKAR following unilateral and bilateral podokinetic (PK) stimulation to determine whether the left and right legs could be independently adapted. Each subject performed two sessions of PK stimulation, stepping in place with one foot on either side of the axis of a rotating disk. Subjects experienced bilateral stimulation (i.e., both left and right feet stepped on the rotating disk) in one session and unilateral stimulation (i.e., the left foot stepped on the rotating disk and the right foot stepped on a stationary surface) in the other. Following stimulation, we recorded foot lift-off and touchdown times and pelvic angular velocity while subjects stepped in place on a stationary surface. PKAR velocity following unilateral stimulation was lower than that following bilateral stimulation. Following bilateral stimulation, pelvic rotation was in the counterclockwise (CCW) direction during single-limb support on both the left and right sides. Immediately following left unilateral stimulation, subjects demonstrated CCW pelvic rotation during left single-limb support but not during right single-limb support. Across the first 13 strides, the difference between left and right sides diminished; pelvic angular velocity was then CCW during single-limb support on both sides. This suggests that both the adapted left and the unadapted right limb influenced the final PKAR response with information from the two limbs being integrated over the first few strides.
Development and Serotonergic Modulation of NMDA Bursting in Rat Trigeminal Motoneurons
Authors: Hsiao Chie-Fang , Wu Nanping , Levine Michael S. , Chandler Scott H.
Published: May 2017

The development of N-methyl-d-aspartate (NMDA)-induced burst discharge in rat trigeminal motoneurons (TMNs) between postnatal days P1 and P10 was examined using whole cell patch-clamp recording methods in brain slices. Bath application of NMDA (50 μM) induced a Mg2+-dependent rhythmical bursting activity starting around P8. Prior to the onset of bursting, the membrane potential depolarized and the input resistance increased. Hyperpolarization of the membrane potential with extrinsic current demonstrated a narrow window of membrane potential where maintained rhythmical burst discharge was evident. In P1–P4 neurons, NMDA application produced membrane depolarization and a minimal change in input resistance, but no burst activity at any membrane potential. Voltage-clamp analysis indicated that the bursting activity was related to the presence or absence of a voltage-dependent Mg2+ block and induction of a negative slope conductance (NSC) region in the I NMDA- V relationship. Regardless of age, reduction of extracellular Mg2+ from 1 mM to 30 μM enhanced I NMDA at voltages negative to −60 mV. However, in 1 mM Mg2+, P1–P4 neurons were devoid of a prominent NSC region compared with P8–P10 neurons, suggesting that the efficacy of depolarization in unblocking the NMDA receptors increased with age. NMDA bursting was not dependent on calcium influx through voltage-gated calcium channels (VGCC) but did require a minimal concentration of Ca2+ in the bath. Intracellular bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid application suppressed burst discharge completely, suggesting that intracellular Ca2+ directly, or via second-messenger systems, regulates NMDA receptor activity and bursting. Interestingly, NMDA bursting could be induced in P1–P4 neurons by simultaneous bath application of serotonin (5-HT, 10 μM), which by itself did not produce bursting, suggesting an “enabling” role for 5-HT. Voltage-clamp analysis demonstrated that the NMDA/5-HT bursting resulted from induction of an NSC in the I-Vrelationship of total membrane current. 5-HT by itself produced no such effect. The mechanisms for this effect were due to an enhancement of the NSC region of the I NMDA- V relationship and reduction of a presumed leak current by 5-HT. These data indicate that NMDA bursting in trigeminal motoneurons is developmentally regulated and subject to neuromessenger modulation. Control of the Mg2+ sensitivity of the NMDA receptor and voltage-dependent block by neuromessengers could be an effective means to control the efficacy of glutamatergic synaptic drive to motoneurons during rhythmical oral-motor activity at early postnatal ages.
High-Speed VSD Imaging of Visually Evoked Cortical Waves: Decomposition Into Intra- and Intercortical Wave Motions
Authors: Senseman David M. , Robbins Kay A.
Published: May 2017

In the pond turtle, Pseudemys scripta elegans, visually evoked cortical waves propagate at different velocities within the primary visual area compared with waves that pass into the secondary visual area. In an effort to separate intra- and intercortical wave motions, movies of visually evoked cortical waves recorded by high-speed voltage-sensitive dye (VSD) imaging were subjected to Karhunen-Loéve (KL) decomposition. This procedure decomposes the VSD movies into a series of basis images that capture different spatial patterns of coherent activity. Most of the energy of the compound wave motion (>95%) was captured by the three largest basis images, M1,1 , M1,2 , and M2,1 . Based on visual comparison with maps of wave front latency, KL basis image M1,2 appears to capture the spread of depolarization within the primary visual area, whereas KL basis image M2,1 appears to capture the spread of depolarization from the primary into the secondary visual area. The contribution of different basis images to the intra- and intercortical wave motions was tested by reconstructing the response using different combinations of KL basis images. Only KL basis images M1,1 and M1,2 were needed to reconstruct intracortical wave motion, while basis images M1,1 and M2,1 were needed to reconstruct intercortical wave motion. It was also found that the direction and speed of wave propagation could be deduced by visual inspection of the basis image projections on to the original data set. The relative advantage of KL decomposition for the analysis of complex wave motions captured by VSD imaging is discussed.
Spatiotemporal Activation of Lumbosacral Motoneurons in the Locomotor Step Cycle
Authors: Yakovenko Sergiy , Mushahwar Vivian , VanderHorst Veronique , Holstege Gert , Prochazka Arthur
Published: May 2017

The aim of this study was to produce a dynamic model of the spatiotemporal activation of ensembles of alpha motoneurons (MNs) in the cat lumbosacral spinal cord during the locomotor step cycle. The coordinates of MNs of 27 hindlimb muscles of the cat were digitized from transverse sections of spinal cord spanning the entire lumbosacral enlargement from the caudal part of L4 to the rostral part of S1 segments. Outlines of the spinal cord gray matter were also digitized. Models of the spinal cord were generated from these digitized data and displayed on a computer screen as three-dimensional (3-D) images. We compiled a chart of electromyographic (EMG) profiles of the same 27 muscles during the cat step cycle from previous studies and used these to modulate the number of active MNs in the 3-D images. The step cycle was divided into 100 equal intervals corresponding to about 7 ms each for gait of moderate speed. For each of these 100 intervals, the level of EMG of each muscle was used to scale the number of dots displayed randomly within the volume of the corresponding MN pool in the digital model. One hundred images of the spinal cord were thereby generated, and these could be played in sequence as a continuous-loop movie representing rhythmical stepping. A rostrocaudal oscillation of activity in hindlimb MN pools emerged. This was confirmed by computing the locus of the center of activation of the MNs in the 100 consecutive frames of the movie. The caudal third of the lumbosacral enlargement showed intense MN activity during the stance phase of locomotion. During the swing phase, the focus of activation shifted abruptly to the rostral part of the enlargement. At the stance-swing transition, a transient focus of activity formed in the most caudal part of the lumbosacral enlargement. This was associated with activation of gracilis, posterior biceps, posterior semimembranosus, and semitendinosus muscles. These muscles move the foot back and up to clear the ground during locomotion, a role that could be described as retraction. The spatiotemporal distribution of neuronal activity in the spinal cord during normal locomotion with descending control and sensory inputs intact has not been visualized before. The model can be used in the future to characterize spatiotemporal activity of spinal MNs in the absence of descending and sensory inputs and to compare these to spatiotemporal patterns in spinal MNs in normal locomotion.