bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial Uncoupling of Neurotransmitter Release From [Ca2+]iby Membrane Hyperpolarization
Authors: Ravin R. , Parnas H. , Spira M. E. , Parnas I.
Published: December 2017

Partial uncoupling of neurotransmitter release from [Ca2+]iby membrane hyperpolarization. The dependence of evoked and asynchronous release on intracellular calcium ([Ca2+]i) and presynaptic membrane potential was examined in single-release boutons of the crayfish opener neuromuscular junction. When a single bouton was depolarized by a train of pulses, [Ca2+]iincreased to different levels according to the frequency of stimulation. Concomitant measurements of evoked release and asynchronous release, from the same bouton, showed that both increased in a sigmoidal manner as a function of [Ca2+]i. When each of the depolarizing pulses was immediately followed by a hyperpolarizing pulse, [Ca2+]iwas elevated to a lesser degree than in the control experiments, and the rate of asynchronous release and the quantal content were reduced; most importantly, evoked quantal release terminated sooner. The diminution of neurotransmitter release by the hyperpolarizing postpulse (HPP) could not be entirely accounted for by the reduction in [Ca2+]i. The experimental results are consistent with the hypothesis that the HPP reduces the sensitivity of the release machinery to [Ca2+]i, thereby not only reducing the quantal content but also terminating the quantal release process sooner.
Failure of Cerebellar Patients to Time Finger Opening Precisely Causes Ball High-Low Inaccuracy in Overarm Throws
Authors: Timmann D. , Watts S. , Hore J.
Published: December 2017

We investigated the idea that the cerebellum is required for precise timing of fast skilled arm movements by studying one situation where timing precision is required, namely finger opening in overarm throwing. Specifically, we tested the hypothesis that in overarm throws made by cerebellar patients, ball high-low inaccuracy is due to disordered timing of finger opening. Six cerebellar patients and six matched control subjects were instructed to throw tennis balls at three different speeds from a seated position while angular positions in three dimensions of five arm segments were recorded at 1,000 Hz with the search-coil technique. Cerebellar patients threw more slowly than controls, were markedly less accurate, had more variable hand trajectories, and showed increased variability in the timing, amplitude, and velocity of finger opening. Ball high-low inaccuracy was not related to variability in the height or direction of the hand trajectory or to variability in finger amplitude or velocity. Instead, the cause was variable timing of finger opening and thereby ball release occurring on a flattened arc hand trajectory. The ranges of finger opening times and ball release times (timing windows) for 95% of the throws were on average four to five times longer for cerebellar patients; e.g., across subjects mean ball release timing windows for throws made under the medium-speed instruction were 11 ms for controls and 55 ms for cerebellar patients. This increased timing variability could not be explained by disorder in control of force at the fingers. Because finger opening in throwing is likely controlled by a central command, the results implicate the cerebellum in timing the central command that initiates finger opening in this fast skilled multijoint arm movement.
Single-Unit Responses in the Inferior Colliculus of Decerebrate Cats I. Classification Based on Frequency Response Maps
Authors: Ramachandran Ramnarayan , Davis Kevin A. , May Bradford J.
Published: December 2017

This study proposes a classification system for neurons in the central nucleus of the inferior colliculus (ICC) that is based on excitation and inhibition patterns of single-unit responses in decerebrate cats. The decerebrate preparation allowed extensive characterization of physiological response types without the confounding effects of anesthesia. The tone-driven discharge rates of individual units were measured across a range of frequencies and levels to map excitatory and inhibitory response areas for contralateral monaural stimulation. The resulting frequency response maps can be grouped into the following three populations: type V maps exhibit a wide V-shaped excitatory area and no inhibition; type I maps show a more restricted I-shaped region of excitation that is flanked by inhibition at lower and higher frequencies; and type O maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Units that produce a type V map typically have a low best frequency (BF: the most sensitive frequency), a low rate of spontaneous activity, and monotonic rate-level functions for both BF tones and broadband noise. Type I and type O units have BFs that span the cat’s range of audible frequencies and high rates of spontaneous activity. Like type V units, type I units are excited by BF tones and noise at all levels, but their rate-level functions may become nonmonotonic at high levels. Type O units are inhibited by BF tones and noise at high levels. The existence of distinct response types is consistent with a conceptual model in which the unit types receive dominant inputs from different sources and shows that these functionally segregated pathways are specialized to play complementary roles in the processing of auditory information.
Single-Unit Responses in the Inferior Colliculus of Decerebrate Cats II. Sensitivity to Interaural Level Differences
Authors: Davis Kevin A. , Ramachandran Ramnarayan , May Bradford J.
Published: December 2017

Single units in the central nucleus of the inferior colliculus (ICC) of unanesthetized decerebrate cats can be grouped into three distinct types (V, I, and O) according to the patterns of excitation and inhibition revealed in contralateral frequency response maps. This study extends the description of these response types by assessing their ipsilateral and binaural response map properties. Here the nature of ipsilateral inputs is evaluated directly using frequency response maps and compared with results obtained from methods that rely on sensitivity to interaural level differences (ILDs). In general, there is a one-to-one correspondence between observed ipsilateral input characteristics and those inferred from ILD manipulations. Type V units receive ipsilateral excitation and show binaural facilitation (EE properties); type I and type O units receive ipsilateral inhibition and show binaural excitatory/inhibitory (EI) interactions. Analyses of binaural frequency response maps show that these ILD effects extend over the entire receptive field of ICC units. Thus the range of frequencies that elicits excitation from type V units is expanded with increasing levels of ipsilateral stimulation, whereas the excitatory bandwidth of type I and O units decreases under the same binaural conditions. For the majority of ICC units, application of bicuculline, an antagonist for GABAA-mediated inhibition, does not alter the basic effects of binaural stimulation; rather, it primarily increases spontaneous and maximum discharge rates. These results support our previous interpretations of the putative dominant inputs to ICC response types and have important implications for midbrain processing of competing free-field sounds that reach the listener with different directional signatures.
Nonlinear Frequency-Dependent Synchronization in the Developing Hippocampus
Authors: Prida Liset Menendez de la , Sanchez-Andres Juan V.
Published: December 2017

Synchronous population activity is present both in normal and pathological conditions such as epilepsy. In the immature hippocampus, synchronous bursting is an electrophysiological conspicuous event. These bursts, known as giant depolarizing potentials (GDPs), are generated by the synchronized activation of interneurons and pyramidal cells via GABAA, N-methyl-d-aspartate, and AMPA receptors. Nevertheless the mechanism leading to this synchronization is still controversial. We have investigated the conditions under which synchronization arises in developing hippocampal networks. By means of simultaneous intracellular recordings, we show that GDPs result from local cooperation of active cells within an integration period prior to their onset. During this time interval, an increase in the number of excitatory postsynaptic potentials (EPSPs) takes place building up full synchronization between cells. These EPSPs are correlated with individual action potentials simultaneously occurring in neighboring cells. We have used EPSP frequency as an indicator of the neuronal activity underlying GDP generation. By comparing EPSP frequency with the occurrence of synchronized GDPs between CA3 and the fascia dentata (FD), we found that GDPs are fired in an all-or-none manner, which is characterized by a specific threshold of EPSP frequency from which synchronous GDPs emerge. In FD, the EPSP frequency-threshold for GDP onset is 17 Hz. GDPs are triggered similarly in CA3 by appropriate periodic stimulation of mossy fibers. The frequency threshold for CA3 GDP onset is 12 Hz. These findings clarify the local mechanism of synchronization underlying bursting in the developing hippocampus, indicating that GDPs are fired when background levels of EPSPs or action potentials have built up full synchronization by firing at specific frequencies (>12 Hz). Our results also demonstrate that spontaneous EPSPs and action potentials are important for the initiation of synchronous bursts in the developing hippocampus.
Odorants Suppress a Voltage-Activated K+Conductance in Rat Olfactory Neurons
Authors: Lischka Fritz W. , Teeter John H. , Restrepo Diego
Published: December 2017

Stimulation of olfactory receptor neurons (ORNs) with odors elicits an increase in the concentration of cAMP leading to opening of cyclic nucleotide-gated (CNG) channels and subsequent depolarization. Although opening of CNG channels is thought to be the main mechanism mediating signal transduction, modulation of other ion conductances by odorants has been postulated. To determine whether K+conductances are modulated by odorants in mammalian ORNs, we examined the response of rat ORNs to odors by recording membrane current under perforated-patch conditions. We find that rat ORNs display two predominant types of responses. Thirty percent of the cells responded to odorants with activation of a CNG conductance. In contrast, in 55% of the ORNs, stimulation with odorants inhibited a voltage-activated K+conductance ( IKo). In terms of pharmacology, ion permeation, outward rectification, and time course for inactivation, IKoresembled a delayed rectifier K+conductance. The effect of odorants on IKowas specific (only certain odorants inhibited IKoin each ORN) and concentration dependent, and there was a significant latency between arrival of odorants to the cell and the onset of suppression. These results indicate that indirect suppression of a K+conductance ( IKo) by odorants plays a role in signal transduction in mammalian ORNs.
Stimulation of a Restricted Region in the Midline Cerebellar White Matter Evokes Coordinated Quadrupedal Locomotion in the Decerebrate Cat
Authors: Mori Shigemi , Matsui Toshihiro , Kuze Bunya , Asanome Mitsuru , Nakajima Katsumi , Matsuyama Kiyoji
Published: December 2017

In the reflexively standing acute decerebrate cat, we have previously shown that pulse train microstimulation of the hook bundle of Russel in the midline of the cerebellar white matter, through which crossed fastigiofugal fibers decussate, augments the postural tone of neck, trunk, fore-, and hindlimb extensor muscles. In the present study we examined the possible role of such stimulation in evoking locomotion as the animal is supported by a rubber hammock with its feet contacting the moving surface of a treadmill. We were able to provoke well-coordinated, bilaterally symmetrical, fore- and hindlimb movements, whose cycle time and pattern were controlled by appropriate changes in stimulus intensity and treadmill speed. We carefully and systematically mapped this cerebellar locomotor region (CLR) through repeated dorsoventral penetrations with a glass-coated tungsten microelectrode in a single animal and between animals. We found that the optimal locus for evoking locomotion was centered on the midline, at Horsley-Clarke coordinates H0 and P7.0, and extended over a rostrocaudal and dorsolateral range of ∼0.5 mm. The lowest effective stimulus intensity at the optimal site was in the range of 5–8 μA. Along penetration tracks to left or right of the midline, effective stimulus intensity increased and evoked locomotor patterns were no longer symmetrical, but rather shifted toward the contralateral limbs. In the same animals, controlled locomotion was evoked by stimulating the mesencephalic locomotor region (MLR). With concomitant stimulation of the optimal sites in the CLR and the MLR, each at subthreshold strength, locomotor movements identical to those seen with suprathreshold stimulation of each site alone were evoked. With concomitant stimulation at suprathreshold strength for each site, locomotion became vigorous, with a shortened cycle time. After making ablative lesions at either the CLR or MLR (unilateral or bilateral), controlled locomotion was still evoked at the prior stimulus strength by stimulating the remaining site. Together, these results demonstrate that selective stimulation of the hook bundle of Russel in the midsagittal plane of the cerebellar white matter evokes “controlled” locomotion identical to that evoked by stimulating the MLR. We have shown that the fastigial nucleus is one of the supraspinal locomotion inducing sites and that it can independently and simultaneously trigger brain stem and spinal locomotor subprograms formerly believed to be the domain of various brain stem regions including the MLR and the subthalamic locomotor region.
Responses to Auditory Stimuli in Macaque Lateral Intraparietal Area I. Effects of Training
Authors: Grunewald Alexander , Linden Jennifer F. , Andersen Richard A.
Published: December 2017

The lateral intraparietal area (LIP) of macaques has been considered unresponsive to auditory stimulation. Recent reports, however, indicate that neurons in this area respond to auditory stimuli in the context of an auditory-saccade task. Is this difference in auditory responsiveness of LIP due to auditory-saccade training? To address this issue, LIP responses in two monkeys were recorded at two different times: before and after auditory-saccade training. Before auditory-saccade training, the animals had never been trained on any auditory task, but had been trained on visual tasks. In both sets of experiments, activity of LIP neurons was recorded while auditory and visual stimuli were presented and the animals were fixating. Before training, 172 LIP neurons were recorded. Among these, the number of cells responding to auditory stimuli did not reach significance, whereas about one-half of the cells responded to visual stimuli. An information theory analysis confirmed that no information about auditory stimulus location was available in LIP neurons in the experiments before training. After training, activity from 160 cells was recorded. These experiments showed that 12% of cells in area LIP responded to auditory stimuli, whereas the proportion of cells responding to visual stimuli remained about the same as before training. The information theory analysis confirmed that, after training, information about auditory stimulus location was available in LIP neurons. Auditory-saccade training therefore generated responsiveness to auditory stimuli de novo in LIP neurons. Thus some LIP cells become active for auditory stimuli in a passive fixation task, once the animals have learned that these stimuli are important for oculomotor behavior.
Fastigial Nucleus Activity During Different Frequencies and Orientations of Vertical Vestibular Stimulation in the Monkey
Authors: Siebold C. , Kleine J. F. , Glonti L. , Tchelidze T. , Büttner U.
Published: December 2017

Neurons in the rostral part of the fastigial nucleus (FN) respond to vestibular stimulation but are not related to eye movements. To understand the precise role of these vestibular-only neurons in the central processing of vestibular signals, unit activity in the FN of alert monkeys ( Macaca mulatta) was recorded. To induce vestibular stimulation, the monkey was rotated sinusoidally around an earth-fixed horizontal axis at stimulus frequencies between 0.06 (±15°) and 1.4 Hz (±7.5°). During stimulation head orientation was changed continuously, allowing for roll, pitch, and intermediate planes of orientation. At a frequency of 0.6 Hz, 59% of the neurons had an optimal response orientation (ORO) and a null response (i.e., no modulation) 90° apart. The phase of neuronal response was constant except for a steep shift of 180° around the null response. This group I response is compatible with a semicircular canal input, canal convergence, or a single otolith input. Several other features indicated more complex responses, including spatiotemporal convergence (STC). 1) For 35% of the responses at 0.6 Hz, phase changes were gradual with different orientations. Fifteen percent of these had a null response (group II), and 20% showed only a minimal response but no null response (group III). The remaining responses (6%), classified as group IV, were characterized by a constant sensitivity at different orientations in most instances. 2) For the vast majority of neurons, the stimulus frequency determined the response group, i.e., an individual neuron could show a group I response at one frequency and a group II (III or IV) response at another frequency. 3) ORO changed with frequency by >45° for 44% of the neurons. 4) Although phase changes at different frequencies were close to head velocity (±45°) or head position (±45°) for most neurons, they exceeded 90° for 29% of the neurons between 0.1 and 1.0 Hz. In most cases, this was a phase advance. The change in sensitivity with change in frequency showed a similar pattern for all neurons; the average sensitivity increased from 1.24 imp · s−1 · deg−1 at 0.1 Hz to 2.97 imp · s−1· deg−1 at 1.0 Hz. These data demonstrate that only an analysis based on measurements at different frequencies and orientations reveals a number of complex features. They moreover suggest that for the vast majority of neurons several sources of canal and otolith information interact at this central stage of vestibular information processing.
Firing Behavior of Vestibular Neurons During Active and Passive Head Movements: Vestibulo-Spinal and Other Non-Eye-Movement Related Neurons
Authors: McCrea Robert A. , Gdowski Greg T. , Boyle Richard , Belton Timothy
Published: December 2017

The firing behavior of 51 non-eye movement related central vestibular neurons that were sensitive to passive head rotation in the plane of the horizontal semicircular canal was studied in three squirrel monkeys whose heads were free to move in the horizontal plane. Unit sensitivity to active head movements during spontaneous gaze saccades was compared with sensitivity to passive head rotation. Most units (29/35 tested) were activated at monosynaptic latencies following electrical stimulation of the ipsilateral vestibular nerve. Nine were vestibulo-spinal units that were antidromically activated following electrical stimulation of the ventromedial funiculi of the spinal cord at C1. All of the units were less sensitive to active head movements than to passive whole body rotation. In the majority of cells (37/51, 73%), including all nine identified vestibulo-spinal units, the vestibular signals related to active head movements were canceled. The remaining units ( n = 14, 27%) were sensitive to active head movements, but their responses were attenuated by 20–75%. Most units were nearly as sensitive to passive head-on-trunk rotation as they were to whole body rotation; this suggests that vestibular signals related to active head movements were cancelled primarily by subtraction of a head movement efference copy signal. The sensitivity of most units to passive whole body rotation was unchanged during gaze saccades. A fundamental feature of sensory processing is the ability to distinguish between self-generated and externally induced sensory events. Our observations suggest that the distinction is made at an early stage of processing in the vestibular system.
Geometry of Dendritic Spines Affects Calcium Dynamics in Hippocampal Neurons: Theory and Experiments
Authors: Volfovsky N. , Parnas H. , Segal M. , Korkotian E.
Published: December 2017

The role of dendritic spine morphology in the regulation of the spatiotemporal distribution of free intracellular calcium concentration ([Ca2+]i) was examined in a unique axial-symmetrical model that focuses on spine–dendrite interactions, and the simulations of the model were compared with the behavior of real dendritic spines in cultured hippocampal neurons. A set of nonlinear differential equations describes the behavior of a spherical dendritic spine head, linked to a dendrite via a cylindrical spine neck. Mechanisms for handling of calcium (including internal stores, buffers, and efflux pathways) are placed in both the dendrites and spines. In response to a calcium surge, the magnitude and time course of the response in both the spine and the parent dendrite vary as a function of the length of the spine neck such that a short neck increases the magnitude of the response in the dendrite and speeds up the recovery in the spine head. The generality of the model, originally constructed for a case of release of calcium from stores, was tested in simulations of fast calcium influx through membrane channels and verified the impact of spine neck on calcium dynamics. Spatiotemporal distributions of [Ca2+]i, measured in individual dendritic spines of cultured hippocampal neurons injected with Calcium Green-1, were monitored with a confocal laser scanning microscope. Line scans of spines and dendrites at a <1-ms time resolution reveal simultaneous transient rises in [Ca2+]i in spines and their parent dendrites after application of caffeine or during spontaneous calcium transients associated with synaptic or action potential discharges. The magnitude of responses in the individual compartments, spine–dendrite disparity, and the temporal distribution of [Ca2+]i were different for spines with short and long necks, with the latter being more independent of the dendrite, in agreement with prediction of the model.
Movement-Related Cerebellar Activation in the Absence of Sensory Input
Authors: Weeks Robert A. , Gerloff Christian , Honda Manabu , Dalakas Marinos C. , Hallett Mark
Published: December 2017

Movement-related cerebellar activation may be due to sensory or motor processing. Ordinarily, sensory and motor processing are obligatorily linked, but in patients who have severe pansensory neuropathies with normal muscle strength, motor activity occurs in isolation. In the present study, positron emission tomography and functional magnetic resonance imaging in such patients showed no cerebellar activation with passive movement, whereas there was prominent movement-related cerebellar activation despite absence of proprioceptive or visual input. The results indicate that motor processing occurs within the cerebellum and do not support the recently advanced view that the cerebellum is primarily a sensory organ.
Motor Unit Substitution in Long-Duration Contractions of the Human Trapezius Muscle
Authors: Westgaard R. H. , de Luca C. J.
Published: December 2017

We examined the activity pattern of low-threshold motor units in the human trapezius muscle during contractions of 10 min duration. Three procedures were applied in sequence: 1) static contraction controlled by maintaining a constant low level of the surface electromyogram (EMG)-detected root-mean-square signal, 2) a manipulation task with mental concentration, and 3) copying a text on a word processor. A quadrifilar fine-wire electrode was used to record single motor unit activity. Simultaneously, surface electrodes recorded the surface EMG signal. During these contractions, low-threshold motor units showed periods of inactivity and were substituted by motor units of higher recruitment threshold. This phenomenon was not observed during the first few minutes of the contraction. In several cases the substitution process coincided with a short period of inactivity in the surface EMG pattern. Substitution was observed in five of eight experiments. These observations may be explained by a time-variant recruitment threshold of motor units, sensitive to their activation history and temporal variation in the activity patterns. We speculate that the substitution phenomenon protects motor units in postural muscles from excessive fatigue when there is a demand for sustained low-level muscle activity.
Oxidative Downmodulation of the Transient K-CurrentI A by Intracellular Arachidonic Acid in Rat Hippocampal Neurons
Authors: Bittner Katrin , Müller Wolfgang
Published: December 2017

Membrane-permeable arachidonic acid (AA) is liberated in a Ca2+-dependent way inside cells. By using whole cell patch clamp we show that intracellular AA (1 pM) selectively reduces I A in rat hippocampal neurons, whereas extracellular application requires a 106-fold concentration. The nonmetabolized AA analogue ETYA mimics the effect of AA that is blocked by ascorbic acid or intracellular glutathione, suggesting an intracellular oxidative mechanism. We conclude that intracellular AA is extremely potent in reducing I A by an oxidative mechanism, particularly during oxidative stress.
Physiological Studies of Spinohypothalamic Tract Neurons in the Lumbar Enlargement of Monkeys
Authors: Zhang X. , Wenk H. N. , Gokin A. P. , Honda C. N. , Giesler G. J.
Published: December 2017

Recent anatomic results indicate that a large direct projection from the spinal cord to the hypothalamus exists in monkeys. The aim of this study was to determine whether the existence of this projection could be confirmed unambiguously using electrophysiological methods and, if so, to determine the response characteristics of primate spinohypothalamic tract (SHT) neurons. Fifteen neurons in the lumbar enlargement of macaque monkeys were antidromically activated using low-amplitude current pulses in the contralateral hypothalamus. The points at which antidromic activation thresholds were lowest were found in the supraoptic decussation ( n = 13) or in the medial hypothalamus ( n = 2). Recording points were located in the superficial dorsal horn ( n = 1), deep dorsal horn ( n = 10), and intermediate zone ( n = 4). Each of the 12 examined neurons had cutaneous receptive fields on the ipsilateral hindlimb. All neurons responded exclusively or preferentially to noxious stimuli, suggesting that the transmission of nociceptive information is an important role of primate SHT axons. Twelve SHT neurons were also antidromically activated from the thalamus. In all cases, the antidromic latency from the thalamus was shorter than that from the hypothalamus, suggesting that the axons pass through the thalamus then enter the hypothalamus. These results confirm the existence of a SHT in primates and suggest that this projection may contribute to the production of autonomic, neuroendocrine, and emotional responses to noxious stimuli in primates, possibly including humans.
Effects of Local Inactivation of Monkey Medial Frontal Cortex in Learning of Sequential Procedures
Authors: Nakamura Kae , Sakai Katsuyuki , Hikosaka Okihide
Published: December 2017

To examine the role of the medial frontal cortex, supplementary motor area (SMA), and pre-SMA in the acquisition and control of sequential movements, we locally injected muscimol into 43 sites in the medial frontal cortex while monkeys (n = 2) performed a sequential button-press task. In this task, the monkey had to press two of 16 (4 × 4 matrix) buttons illuminated simultaneously in a predetermined order. A total of five pairs were presented in a fixed order for completion of a trial. To clarify the differential contribution of the medial frontal cortex for new acquisition and control of sequential movements, we used novel and learned sequences (that had been learned after extensive practice). We found that the number of errors increased for novel sequences, but not for learned sequences, after pre-SMA inactivations. A similar, but insignificant, trend was observed after SMA injections. The reaction time of button presses for both novel and learned sequences was prolonged by inactivations of both SMA and pre-SMA, with a trend for the effect to be larger for SMA inactivations. These findings suggest that the medial frontal cortex, especially pre-SMA, is related to the acquisition, rather than the storage or execution, of the correct order of button presses.
Errors of Memory-Guided Saccades in Humans With Lesions of the Frontal Eye Field and the Dorsolateral Prefrontal Cortex
Authors: Ploner Christoph J. , Rivaud-Péchoux Sophie , Gaymard Bertrand M. , Agid Yves , Pierrot-Deseilligny Charles
Published: December 2017

Behavioral studies in monkeys and humans suggest that systematic and variable errors of memory-guided saccades reflect distinct neuronal computations in primate spatial memory. We recorded memory-guided saccades with a 2-s delay in three patients with unilateral ischemic lesions of the frontal eye field and in three patients with unilateral ischemic lesions of the frontal eye field and the dorsolateral prefrontal cortex. Results suggest that systematic errors of memory-guided saccades originate in the frontal eye field and variable errors in the dorsolateral prefrontal cortex. These data are the first human lesion data to support the hypothesis that these regions provide functionally distinct contributions to spatial short-term memory.
Cholinergic Synaptic Transmission in Insect Mushroom Bodies In Vitro
Authors: Oleskevich Sharon
Published: December 2017

The mushroom body of the bee brain is an important site for learning and memory. Here we investigate synaptic transmission in the mushroom body using extracellular recording techniques in a whole bee brain in vitro preparation. The postsynaptic response showed attenuation by cadmium and paired-pulse facilitation, similar to in vivo findings. This confirms the viability of the in vitro preparation and supports the isolated whole bee brain as a useful model of the in vivo preparation. Bath application of the acetylcholine receptor antagonists, d-tubocurarine and α-bungarotoxin attenuated the postsynaptic response by 61 and 62% of control, respectively. The glutamate receptor antagonists, (+)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, had no effect. The invertebrate monoamine and neuromodulator, octopamine, transiently increased the postsynaptic response by 130% of control. These results suggest that synaptic transmission of the olfactory input pathway in the mushroom body is 1) mediated primarily by acetylcholine and 2) modulated by octopamine.
Requirements for LTP Induction by Pairing in Hippocampal CA1 Pyramidal Cells
Authors: Chen Huan-Xin , Otmakhov Nikolai , Lisman John
Published: December 2017

The induction of long-term potentiation (LTP) in the hippocampal CA1 region requires both presynaptic activity and large postsynaptic depolarization. A standard protocol for inducing LTP using whole-cell recording is to pair low-frequency synaptic stimulation (100–200 pulses, 1–2 Hz) with a depolarizing voltage-clamp pulse (1–3 min duration). In this standard protocol, a Cs+-based internal solution is used to improve the fidelity of the depolarization produced by voltage-clamp. In an attempt to induce LTP more rapidly, we tried to induce LTP by pairing high-frequency stimulation (200 pulses, 20–100 Hz) with a short depolarization (∼15 s). Surprisingly, we found that this protocol failed to induce LTP, even though large LTP (∼300% of baseline) could be induced by a subsequent standard protocol in the same cell. Pairing brief high-frequency stimulation at the beginning of a long depolarization (3 min) also did not induce LTP. However, the same high-frequency stimulation at the end of the long depolarization did induce LTP. When similar experiments were done with a K+-based internal solution, pairing high-frequency stimulation with a short depolarization did induce LTP. This indicates that the requirement for long depolarization is related to the use of Cs+. We speculate that, when recording is made with Cs+, a tetanus given at the beginning of depolarization initiates a process that inhibits N-methyl-d-aspartate (NMDA)–dependent LTP. This inhibitory process itself decays away during prolonged depolarization.
Serotonin Modulates Glutamate Responses in Isolated Suprachiasmatic Nucleus Neurons
Authors: Quintero Jorge E. , McMahon Douglas G.
Published: December 2017

Two input pathways to the suprachiasmatic nucleus (SCN) of the hypothalamus are the glutamatergic retinohypothalamic tract and the serotonergic afferent from the midbrain raphe nucleus. To determine whether these two temporal signaling pathways can converge at the cellular level, we have investigated the effects of serotonin on glutamate-induced calcium responses of individual SCN neurons isolated in cell culture. Dispersed cultures were formed from the SCN of neonatal rats. The calcium indicator Fura-2 acetoxymethyl ester was used to assess the changes in [Ca2+]iby recording the 340-nm/380-nm excitation ratio. Application of glutamate (5 μM) to the culture caused a rapid (within 10 s) increase in the fluorescence ratio of neurons indicating a marked increase in the concentration of intracellular free calcium. However, when 5-hydroxytryptamine (5-HT; 5 μM) was coapplied with glutamate, 31% of neurons showed an overall 61% reduction in the peak of the glutamate-induced calcium increase. Application of the 5-HT7/1Areceptor agonist, (±)-8-hydroxy-2-(di- n-propylamino)tetralin [(±)-8-OH-DPAT] (1 μM), also reduced the calcium elevation this time by 80% in 18% of the neurons tested. When the 5-HT7/2/1Creceptor antagonist, ritanserin (800 nM), was coapplied with serotonin, it blocked modulation of the glutamate responses. Further support for the involvement of the 5-HT7receptor was provided by the ability of the adenylate cyclase activator, forskolin (10 μM), and the cAMP analogue, 8-Br cAMP (0.5 mM), to mimic the suppressive effect of serotonin. Blocking spike-mediated cell communication with tetrodotoxin (1 μM) did not prevent the serotonergic suppression of glutamate-induced responses. These results support the hypothesis that the serotonergic modulation of photic entraining signals can occur in SCN neurons.
Multiple Components of Ipsilaterally Evoked Inhibition in the Inferior Colliculus
Authors: Klug Achim , Bauer Eric E. , Pollak George D.
Published: December 2017

The central nucleus of the inferior colliculus (ICc) receives a large number of convergent inputs that are both excitatory and inhibitory. Although excitatory inputs typically are evoked by stimulation of the contralateral ear, inhibitory inputs can be recruited by either ear. Here we evaluate ipsilaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. The principal question we addressed concerns the degree to which ipsilateral inhibition at the ICc suppresses contralaterally evoked discharges and thus creates the excitatory-inhibitory (EI) properties of ICc neurons. To study ipsilaterally evoked inhibition, we iontophoretically applied excitatory neurotransmitters and visualized the ipsilateral inhibition as a gap in the carpet of background activity evoked by the transmitters. Ipsilateral inhibition was seen in 86% of ICc cells. The inhibition in most cells had both glycinergic and GABAergic components that could be blocked by the iontophoretic application of bicuculline and strychnine. In 80% of the cells that were inhibited, the ipsilateral inhibition and contralateral excitation were temporally coincident. In many of these cells, the ipsilateral inhibition suppressed contralateral discharges and thus generated the cell’s EI property in the ICc. In other cells, the ipsilateral inhibition was coincident with the initial portion of the excitation, but the inhibition was only 2–4 ms in duration and suppressed only the first few contralaterally evoked discharges. The suppression was so slight that it often could not be detected as a decrease in the spike count generated by increasing ipsilateral intensities. Twenty percent of the cells that expressed inhibition, however, had inhibitory latencies that were longer than the excitatory latencies. In these neurons, the inhibition arrived too late to suppress most or any of the discharges. Finally, in the majority of cells, the ipsilateral inhibition persisted for tens of milliseconds beyond the duration of the signal that evoked it. Thus ipsilateral inhibition has multiple components and one or more of these components are typically evoked in ICc neurons by sound received at the ipsilateral ear.
Serotonergic Modulation of the Hyperpolarizing Spike Afterpotential in Rat Jaw-Closing Motoneurons by PKA and PKC
Authors: Inoue Tomio , Itoh Satsuki , Kobayashi Masayuki , Kang Youngnam , Matsuo Ryuji , Wakisaka Satoshi , Morimoto Toshifumi
Published: December 2017

Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 μM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 μM). On the other hand, when the mAHP amplitude was increased by raising [Ca2+]ofrom 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 μM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 μM 5-HT under raised [Ca2+]owas blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT1Aantagonist NAN-190 or 5-HT4antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca2+]o. Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.
Phase-Dependent Inhibition of H-Reflexes During Walking in Humans Is Independent of Reduction in Knee Angular Velocity
Authors: Garrett M. , Kerr T. , Caulfield B.
Published: December 2017

The purpose of this investigation was to investigate whether reduction in impulses arising from stretch of the quadriceps by restricting rapid knee flexion in early swing would affect inhibition of the H-reflex during swing. The contribution of afferent input arising from knee angular velocity to phase-dependent modulation of short-latency responses in the soleus was studied by simultaneously measuring joint velocity and soleus H-reflex responses at midstance and midswing phases of treadmill walking in 15 normal subjects. Stimulus strength was varied so that both maximal M and H waves were identified in each subject at midswing and midstance with the knee unrestricted (UK) and with knee movement restricted (RK), using a full leg bivalved cast to immobilize the knee joint. All subjects exhibited short-latency reflex responses in the soleus muscle. The H/M ratio at midswing was significantly reduced compared with midstance under both UK and RK walking conditions ( P < 0.0001). When compared with UK walking, knee joint angular velocity during RK walking was significantly reduced at midswing ( P < 0.001) and midstance ( P < 0.005) compared with UK. There were, however, no significant differences in H/M ratios at midswing and midstance between UK and RK walking tests. Inhibition of the H-reflex in the soleus muscle during swing was not affected by significant reduction in knee angular velocity. These results indicate that the sensory input from changes in angular velocity at the knee does not lay the inhibitory foundation of phase-related reflex modulation in the ankle extensors during walking as suggested by Brooke and colleagues.
Vertical Purkinje Cells of the Monkey Floccular Lobe: Simple-Spike Activity During Pursuit and Passive Whole Body Rotation
Authors: Fukushima Kikuro , Fukushima Junko , Kaneko Chris R. S. , Fuchs Albert F.
Published: December 2017

To understand how the simian floccular lobe is involved in vertical smooth pursuit eye movements and the vertical vestibuloocular reflex (VOR), we examined simple-spike activity of 70 Purkinje (P) cells during pursuit eye movements and passive whole body rotation. Fifty-eight cells responded during vertical and 12 during horizontal pursuit. We classified P cells as vertical gaze velocity (VG˙) if their modulation occurred for movements of both the eye (during vertical pursuit) and head (during pitch VOR suppression) with the modulation during one less than twice that of the other and was less during the target-fixed-in-space condition (pitch VOR X1) than during pitch VOR suppression. VG˙ P cells constituted only a minority of vertical P cells (19%). Other vertical P cells that responded during pitch VOR suppression were classified as vertical eye and head velocity (VE˙/H˙) P cells (48%), regardless of the synergy of their response direction during smooth pursuit and VOR suppression. Vertical P cells that did not respond during pitch VOR suppression but did respond during rotation in vertical planes other than pitch were classified as off-pitch VE˙/H˙ P cells (33%). The mean eye-velocity and eye-position sensitivities of the three types of vertical P cells were similar. One-third (2/7 VG˙, 2/11 VE˙/H˙, 6/13 off-pitch VE˙/H˙), in addition, showed eye position sensitivity during saccade-free fixations. Maximal vestibular activation directions (MADs) were examined during VOR suppression by applying vertical whole body rotation with the monkeys oriented in different vertical planes. The MADs for VG˙ P cells and VE˙/H˙ P cells with eye and vestibular sensitivity in the same direction were distributed near the pitch plane, suggesting convergence of bilateral anterior canal inputs. In contrast, MADs of off-pitch VE˙/H˙ P cells and VE˙/H˙ P cells with oppositely directed eye and vestibular sensitivity were shifted toward the roll plane, suggesting convergence of anterior and posterior canal inputs of the same side. Unlike horizontal G˙ P cells, the modulation of many VG˙ and VE˙/H˙ P cells when the target was fixed in space (pitch VOR X1) was not well predicted by the linear addition of their modulations during vertical pursuit and pitch VOR suppression. These results indicate that the populations of vertical and horizontal eye-movement P cells in the floccular lobe have markedly different discharge properties and therefore may be involved in different kinds of processing of vestibular-oculomotor interactions.
Differential Patterns of Spinal Sympathetic Outflow Involving a 10-Hz Rhythm
Authors: Gebber Gerard L. , Zhong Sheng , Lewis Craig , Barman Susan M.
Published: December 2017

Time and frequency domain analyses were used to examine the changes in the relationships between the discharges of the inferior cardiac (CN) and vertebral (VN) postganglionic sympathetic nerves produced by electrical activation of the midbrain periaqueductal gray (PAG) in urethan-anesthetized, baroreceptor-denervated cats. CN-VN coherence and phase angle in the 10-Hz band served as measures of the coupling of the central oscillators controlling these nerves. The 10-Hz rhythm in CN and VN discharges was entrained 1:1 to electrical stimuli applied to the PAG at frequencies between 7 and 12 Hz. CN 10-Hz discharges were increased, and VN 10-Hz discharges were decreased when the frequency of PAG stimulation was equal to or above that of the free-running rhythm. In contrast, stimulation of the same PAG sites at lower frequencies increased, albeit disproportionately, the 10-Hz discharges of both nerves. In either case, PAG stimulation significantly increased the phase angle between the two signals (VN 10-Hz activity lagged CN activity); coherence values relating their discharges were little affected. However, the increase in phase angle was significantly more pronounced when the 10-Hz discharges of the two nerves were reciprocally affected. Importantly, partialization of the phase spectrum using the PAG stimuli did not reverse the change in CN-VN phase angle. This observation suggests that the increase in the CN-VN phase angle reflected changes in the phase relations between coupled oscillators in the brain stem rather than the difference in conduction times to the two nerves from the site of PAG stimulation. In contrast to the effects elicited by PAG stimulation, stimulation of the medullary lateral tegmental field induced uniform increases in the 10-Hz discharges of the two nerves and no change in the CN-VN phase angle. Our results demonstrate that changes in the phase relations among coupled brain stem 10-Hz oscillators are accompanied by differential patterns of spinal sympathetic outflow. The reciprocal changes in CN and VN discharges produced by PAG stimulation are consistent with the pattern of spinal sympathetic outflow expected during the defense reaction.