bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of the Temporal Envelope of Sounds in the Human Brain
Authors: Giraud Anne-Lise , Lorenzi Christian , Ashburner John , Wable Jocelyne , Johnsrude Ingrid , Frackowiak Richard , Kleinschmidt Andreas
Published: December 2017

The cerebral representation of the temporal envelope of sounds was studied in five normal-hearing subjects using functional magnetic resonance imaging. The stimuli were white noise, sinusoidally amplitude-modulated at frequencies ranging from 4 to 256 Hz. This range includes low AM frequencies (up to 32 Hz) essential for the perception of the manner of articulation and syllabic rate, and high AM frequencies (above 64 Hz) essential for the perception of voicing and prosody. The right lower brainstem (superior olivary complex), the right inferior colliculus, the left medial geniculate body, Heschl's gyrus, the superior temporal gyrus, the superior temporal sulcus, and the inferior parietal lobule were specifically responsive to AM. Global tuning curves in these regions suggest that the human auditory system is organized as a hierarchical filter bank, each processing level responding preferentially to a given AM frequency, 256 Hz for the lower brainstem, 32–256 Hz for the inferior colliculus, 16 Hz for the medial geniculate body, 8 Hz for the primary auditory cortex, and 4–8 Hz for secondary regions. The time course of the hemodynamic responses showed sustained and transient components with reverse frequency dependent patterns: the lower the AM frequency the better the fit with a sustained response model, the higher the AM frequency the better the fit with a transient response model. Using cortical maps of best modulation frequency, we demonstrate that the spatial representation of AM frequencies varies according to the response type. Sustained responses yield maps of low frequencies organized in large clusters. Transient responses yield maps of high frequencies represented by a mosaic of small clusters. Very few voxels were tuned to intermediate frequencies (32–64 Hz). We did not find spatial gradients of AM frequencies associated with any response type. Our results suggest that two frequency ranges (up to 16 and 128 Hz and above) are represented in the cortex by different response types. However, the spatial segregation of these two ranges is not systematic. Most cortical regions were tuned to low frequencies and only a few to high frequencies. Yet, voxels that show a preference for low frequencies were also responsive to high frequencies. Overall, our study shows that the temporal envelope of sounds is processed by both distinct (hierarchically organized series of filters) and shared (high and low AM frequencies eliciting different responses at the same cortical locus) neural substrates. This layout suggests that the human auditory system is organized in a parallel fashion that allows a degree of separate routing for groups of AM frequencies conveying different information and preserves a possibility for integration of complementary features in cortical auditory regions.
Activation of the Dorsal Premotor Cortex and Pre-Supplementary Motor Area of Humans During an Auditory Conditional Motor Task
Authors: Kurata Kiyoshi , Tsuji Toshiaki , Naraki Satoshi , Seino Morio , Abe Yoshinao
Published: December 2017

Using functional magnetic resonance imaging (fMRI), we measured regional blood flow to examine which motor areas of the human cerebral cortex are preferentially involved in an auditory conditional motor behavior. As a conditional motor task, randomly selected 330 or 660 Hz tones were presented to the subjects every 1.0 s. The low and high tones indicated that the subjects should initiate three successive opposition movements by tapping together the right thumb and index finger or the right thumb and little finger, respectively. As a control task, the same subjects were asked to alternate the two opposition movements, in response to randomly selected tones that were presented at the same frequencies. Between the two tasks, MRI images were also scanned in the resting state while the tones were presented in the same way. Comparing the images during each of the two tasks with images during the resting state, it was observed that several frontal motor areas, including the primary motor cortex, dorsal premotor cortex (PMd), supplementary motor area (SMA), and pre-SMA, were activated. However, preferential activation during the conditional motor task was observed only in the PMd and pre-SMA of the subjects' left (contralateral) frontal cortex. The PMd has been thought to play an important role in transforming conditional as well as spatial visual cues into corresponding motor responses, but our results suggest that the PMd along with the pre-SMA are the sites where more general and extensive sensorimotor integration takes place.
Search Target Selection in Monkey Prefrontal Cortex
Authors: Hasegawa Ryohei P. , Matsumoto Madoka , Mikami Akichika
Published: December 2017

To explore a visual scene, the brain must detect an object of interest and direct the eyes to it. To investigate the brain's mechanism of saccade target selection, we trained monkeys to perform a visual search task with a response delay and recorded neuronal activity in the prefrontal (PF) cortex. Even though the monkey was not allowed to express its choice until after a delay, the response field of a class of PF neurons was able to differentiate between target and distractors from the very beginning of their response (135 ms). Strong responses were obtained only when the target was presented at the field. Neurons responded much less during a nonsearch task in which saccade target was presented alone in this response field. These results suggest that the PF cortex may be involved in the decision-making process and the focal attention for saccade target selection.
Serotonergic Raphe Magnus Cells That Respond to Noxious Tail Heat Are Not on or off Cells
Authors: Gao Keming , Mason Peggy
Published: December 2017

Pharmacological studies have suggested that serotonergic cells in RM contribute to both the inhibition and facilitation of spinal nociceptive transmission. Physiological studies in the medullary nucleus raphe magnus (RM) and adjacent nucleus reticularis magnocellularis have identified putative nociceptive-inhibitory off cells and nociceptive-facilitatory neurons on cells by their responses to noxious thermal stimulation. The present study was designed to determine 1) whether any serotonergic RM cells respond to noxious thermal stimulation and 2) whether noxious heat-responsive serotonergic cells should be classified ason or off cells. Serotonergic cells ( n = 150) were identified by physiological criteria in anesthetized rats; 30 of 32 cells tested contained serotonin immunoreactivity. Noxious tail heat elicited a neuronal response in less than a quarter of the serotonergic cells. Most serotonergic cells that responded to tail heat were excited ( n = 25), while a small minority of the cells tested were inhibited ( n = 8). The tail heat-evoked responses of serotonergic cells were small in magnitude, averaging five to eight spikes in 10 s. Excitatory responses rarely persisted for more than 10 s, while inhibitory responses rarely persisted for more than 20 s. The tail heat-evoked responses of serotonergic cells were compared to those of non-serotonergic cells ( n = 186). Non-serotonergic cells that responded to noxious tail heat had significantly greater response magnitudes, averaging 75–95 spikes in 10 s, than heat-responsive serotonergic cells. In addition, most heat-responsive non-serotonergic cells responded for at least 30 s after stimulus onset. These results demonstrate that the tail heat-evoked responses of serotonergic RM cells are qualitatively and quantitatively distinct from those of non-serotonergic onand off cells. It is therefore unlikely that serotonergic RM cells, even the subpopulation that responds to noxious tail heat, share a physiological function with on and offcells.
Whiskers, Barrels, and Cortical Efferent Pathways in Gap Crossing by Rats
Authors: Jenkinson Edward W. , Glickstein Mitchell
Published: December 2017

Rats can readily be trained to jump a gap of around 16 cm in the dark and a considerably larger gap in the light for a food reward. In the light, they use vision to estimate the distance to be jumped. In the dark, they use their vibrissae at the farthest distances. Bilateral whisker shaving or barrel field lesions reduce the gap crossed in the dark by about 2 cm. Information from the barrel fields reaches motor areas via cortico-cortical, basal ganglia, or cerebellar pathways. The cells of origin of the ponto-cerebellar pathway are segregated in layer Vb of the barrel field. Efferent axons of Vb cells occupy a central position within the basis pedunculi and terminate on cells in the pontine nuclei. Pontine cells, in turn, project to the cerebellar cortex as mossy fibers. We trained normal rats to cross a gap in the light and in a dark alley that was illuminated with an infra-red source. When the performance was stable, we made unilateral lesions in the central region of the basis pedunculi, which interrupted connections from the barrel field to the pons while leaving cortico-cortical and basal ganglia pathways intact. Whisking was not affected on either side by the lesion, and the rats with unilateral peduncle lesions crossed gaps of the same distance as they did pre-operatively. Shaving the whiskers on the side of the face that retains its input to the pontine nuclei reduced the maximal gap jumped in the dark by the same amount as bilateral whisker shaving. Performance in the light was not affected. Regrowth of the shaved whiskers was associated with the recovery of the maximum distance crossed in the dark. In control cases, shaving the whiskers on the other side of the face did not reduce the distance jumped in the dark or in the light. These results suggest that the cerebellum must receive whisker information from the barrel fields for whisker-guided jumps.
Duration Tuning in the Mouse Auditory Midbrain
Authors: Brand Antje , Urban Reas , Grothe Benedikt
Published: December 2017

Temporal cues, including sound duration, are important for sound identification. Neurons tuned to the duration of pure tones were first discovered in the auditory system of frogs and bats and were discussed as specific adaptations in these animals. More recently duration sensitivity has also been described in the chinchilla midbrain and the cat auditory cortex, indicating that it might be a more general phenomenon than previously thought. However, it is unclear whether duration tuning in mammals is robust in face of changes of stimulus parameters other than duration. Using extracellular single-cell recordings in the mouse inferior colliculus, we found 55% of cells to be sensitive to stimulus duration showing long-pass, short-pass, or band-pass filter characteristics. For most neurons, a change in some other stimulus parameter, (e.g., intensity, frequency, binaural conditions, or using noise instead of pure tones) altered and sometimes abolished duration-tuning characteristics. Thus in many neurons duration tuning is interdependent with other stimulus parameters and, hence, might be context dependent. A small number of inferior colliculus neurons, in particular band-pass neurons, exhibited stable filter characteristics and could therefore be referred to as “duration selective.” These findings support the idea that duration tuning is a general phenomenon in the mammalian auditory system.
Estradiol Modulates Long-Term Synaptic Depression in Female Rat Hippocampus
Authors: Zamani M. Reza , Desmond Nancy L , Levy William B
Published: December 2017

Fluctuating estradiol levels in the adult, female rat modify the anatomical and functional organization of the hippocampal CA1 region. When systemic levels of estradiol are low, e.g., on estrus or in ovariectomized (OVX) rats, long-term synaptic potentiation is difficult to induce in vivo. However, little is known about the role of this ovarian hormone in long-term synaptic depression. Using multiple conditioning paradigms, we assess the magnitude of long-term depression (LTD) at CA3-CA1 synapses in vitro from adult, ovariectomized rats as a function of systemic estradiol replacement. In hippocampal slices from control OVX rats with low levels of estradiol, a low-frequency (2 Hz), asynchronous conditioning stimulation protocol does not produce LTD at 1 h postconditioning. However, this same protocol induces robust LTD in slices from estradiol-treated OVX rats. When the conditioning frequency is increased to 4 Hz, slices from both groups of rats show robust LTD in vitro. At an even higher conditioning frequency (10 Hz), the 2-Hz-based observations are reversed; no consistent changes in synaptic transmission are observed in slices from estradiol-treated OVX rats, but those from control rats (OVX + oil) show robust LTD. Thus estradiol reduces the frequency threshold for LTD induction at the CA3-CA1 synapses. Further, regardless of the conditioning frequency employed, where robust LTD is seen, its induction depends on normally functioning N-methyl-d-aspartate (NMDA) receptors during conditioning. The shift in conditioning frequency needed to elicit LTD is consistent with a decrease in NMDA receptor activation with decreasing estradiol levels.
Topography of EEG Dynamics After Sleep Deprivation in Mice
Authors: Huber Reto , Deboer Tom , Tobler Irene
Published: December 2017

Several recent results show that sleep and sleep regulation are not only global phenomena encompassing the entire brain, but have local features. It is well established that slow-wave activity [SWA; mean electroencephalographic (EEG) power density in the 0.75–4.0 Hz band] in non–rapid eye movement (NREM) sleep is a function of the prior history of sleep and wakefulness. SWA is thought to reflect the homeostatic component of the two-process model of sleep regulation. According to this model, originally formulated for the rat and later extended to human sleep, the timing and structure of sleep are determined by the interaction of a homeostatic Process S and a circadian process. Our aim was to investigate the dynamics of SWA in the EEG of two brain regions (frontal and occipital cortex) after sleep deprivation (SD) in two of the mice strains most often used in gene targeting. C57BL/6J ( n = 9) and 129/Ola ( n = 8) were recorded during a 24-h baseline day, 6-h SD, and 18-h recovery. Both derivations showed a significant increase in SWA in NREM sleep after SD in both strains. In the first hour of recovery, SWA was enhanced more in the frontal derivation than in the occipital derivation and showed a faster decline. This difference resulted in a lower value for the time constant for the decrease of SWA in the frontal derivation (frontal: 10.9 ± 2.1 and 6.8 ± 0.9 h in Ola and C57, respectively; occipital: 16.6 ± 2.1 and 14.1 ± 1.5 h; P < 0.02; for each of the strains; paired t-test). Neither time constant differed significantly between the strains. The subdivision of SWA into a slower and faster band (0.75–2.5 Hz and 2.75–4.0 Hz) further highlighted regional differences in the effect of SD. The lower frequency band had a higher initial value in the frontal derivation than in the occipital derivation in both strains. Moreover, in the higher frequency band a prominent reversal took place so that power in the frontal derivation fell below the occipital values in both strains. Thus our results indicate that there may be differences in the brain in the effects of SD on SWA in mice, suggesting regional differences in the dynamics of the homeostatic component of sleep regulation. The data support the hypothesis that sleep has local, use- or waking-dependent features that are reflected in the EEG, as has been shown for humans and the laboratory rat.
Cellular Mechanisms Underlying Activity Patterns in the Monkey Thalamus During Visual Behavior
Authors: Ramcharan E. J. , Cox C. L. , Zhan X. J. , Sherman S. M. , Gnadt J. W.
Published: December 2017

We show for the first time with in vitro recording that burst firing in thalamic relay cells of the monkey is evoked by activation of voltage-dependent, low threshold Ca2+ spikes (LTSs), as has been described in other mammals. Due to variations in LTS amplitude, the number of action potentials evoked by an LTS could vary between 1 and 8. These data confirm the presence of two modes of firing in the monkey for thalamic relay cells, tonic and burst, the latter related to the activation of LTSs. With these details of the cellular processes underlying burst firing, we could account for many of the firing patterns we recorded from the lateral geniculate nucleus of the thalamus in behaving monkeys. In particular, we found clear evidence of burst firing during alert wakefulness, which had been thought to occur only during sleep or certain pathological states. This makes it likely that the burst firing seen in awake humans has the same cellular basis of LTSs, and this supports previous suggestions that burst firing represents an important relay mode for visual processing.
Excitability Increase Induced by β-Adrenergic Receptor-Mediated Activation of Hyperpolarization-Activated Cation Channels in Rat Cerebellar Basket Cells
Authors: Saitow Fumihito , Konishi Shiro
Published: December 2017

In the preceding paper, we showed that norepinephrine (NE) enhances the spontaneous spike firings in cerebellar interneurons, basket cells (BCs), resulting in an increase in the frequency of BC-spike-triggered inhibitory postsynaptic currents (IPSCs) in Purkinje cells (PCs), and that the effects of NE on GABAergic BCs are mediated by β2-adrenergic receptors. This study aimed to further examine the ionic mechanism underlying the β-adrenoceptor-mediated facilitation of GABAergic transmission at the BC-PC synapses. Using cerebellar slices obtained from 15- to 21-day-old rats and whole cell recordings, we investigated ionic currents in the BCs and the effects of the β-agonist isoproterenol (ISP) as well as forskolin on the BC excitability. Hyperpolarizing voltage steps from a holding potential of −50 mV elicited a hyperpolarization-activated inward current, I h, in the BC. This current exhibited voltage-dependent activation that was accelerated by strong hyperpolarization, displaying two time constants, 84 ± 6 and 310 ± 40 ms, at −100 mV, and was inhibited by 20 μM ZD7288. ISP and forskolin, both at 20 μM, enhanced I h by shifting the activation curve by 5.9 and 9.3 mV toward positive voltages, respectively. Under the current-clamp mode, ISP produced a depolarization of 7 ± 3 mV in BCs and reduced their input resistance to 74 ± 6%. ISP and a cAMP analogue, Rp-cAMP-S, increased the frequency of spontaneous spikes recorded from BCs using the cell-attached mode. The I h inhibitor ZD7288 decreased the BC spike frequency and abolished the ISP-induced increase in spike discharges. The results suggest that NE depolarizes the BCs through β-adrenoceptor-mediated cAMP formation linking it to activation of I h, which is, at least in part, involved in noradrenergic afferent-mediated facilitation of GABAergic synaptic activity at BC-PC connections in the rat cerebellum.
Developmental Switch in Excitability, Ca2+ and K+ Currents of Retinal Ganglion Cells and Their Dendritic Structure
Authors: Olson Andrew J. , Picones Arturo , Korenbrot Juan I.
Published: December 2017

In the retina of teleost fish, continuous neuronal development occurs at the margin, in the peripheral growth zone (PGZ). We prepared tissue slices from the retina of rainbow trout that include the PGZ and that comprise a time line of retinal development, in which cells at progressive stages of differentiation are present side by side. We studied the changes in dendritic structure and voltage-dependent Ca2+, Na+, and K+ currents that occur as ganglion cells mature. The youngest ganglion cells form a distinct bulge. Cells in the bulge have spare and short dendritic trees. Only half express Ca2+ currents and then only high-voltage–activated currents with slow inactivation (HVAslow). Bulge cells are rarely electrically excitable. They express a mixture of rapidly inactivating and noninactivating K+currents (IKA and IKdr). The ganglion cells next organize into a transition zone, consisting of a layered structure two to three nuclei thick, before forming the single layered structure characteristic of the mature retina. In the transition zone, the dendritic arbor is elaborately branched and extends over multiple laminae in the inner plexiform layer, without apparent stratification. The arbor of the mature cells is stratified, and the span of the dendritic arbor is well over five times the cell body's diameter. The electrical properties of cells in the transition and mature zones differ significantly from those in the bulge cells. Correlated with the more elaborate dendritic structures are the expression of both rapidly inactivating HVA (HVAfast) and of low-voltage–activated (LVA) Ca2+ currents and of a high density of Na+ currents that renders the cells electrically excitable. The older ganglion cells also express a slowly activating K+ current (IKsa).
Neuronal Activity in the Supplementary and Presupplementary Motor Areas for Temporal Organization of Multiple Movements
Authors: Shima Keisetsu , Tanji Jun
Published: December 2017

To study how neurons in the medial motor areas participate in performing sequential multiple movements that are individually separated in time, we analyzed neuronal activity in the supplementary (SMA) and presupplementary (pre-SMA) motor areas. Monkeys were trained to perform three different movements separated by waiting times, in four or six different orders. Initially each series of movements was learned during five trials guided by visual signals that indicated the correct movements. The monkeys subsequently executed the three movements in the memorized order without the visual signals. Three types of neuronal activity were of particular interest; these appeared to be crucially involved in sequencing the multiple motor tasks in different orders. First, we found activity changes that were selective for a particular sequence of the three movements that the monkeys were prepared to perform. The sequence-selective activity ceased when the monkeys initiated the first movement. Second, we found interval-selective activity that appeared in the interval between one particular movement and the next. Third, we found neuronal activity representing the rank order of three movements arranged chronologically; that is, the activity differed selectively in the process of preparing the first, second, or third movements in individual trials. The interval-selective activity was more prevalent in the SMA, whereas the rank-order selective activity was more frequently recorded in the pre-SMA. These results suggest how neurons in the SMA and pre-SMA are involved in sequencing multiple movements over time.
Postnatal Development of Electrophysiological Properties of Nucleus Accumbens Neurons
Authors: Belleau Marc L. , Warren Richard A.
Published: December 2017

We have studied the postnatal development of the physiological characteristics of nucleus accumbens (nAcb) neurons in slices from postnatal day 1 ( P1) to P49 rats using the whole cell patch-clamp technique. The majority of neurons (102/108) were physiologically identified as medium spiny (MS) projection neurons, and only these were subjected to detailed analysis. The remaining neurons displayed characteristics suggesting that they were not MS neurons. Around the time of birth and during the first postnatal weeks, the membrane and firing characteristics of MS neurons were quite different from those observed later. These characteristics changed rapidly during the first 3 postnatal weeks, at which point they began to resemble those found in adults. Both whole cell membrane resistance and membrane time constant decreased more than fourfold during the period studied. The resting membrane potential (RMP) also changed significantly from an average of −50 mV around birth to less than −80 mV by the end of the third postnatal week. During the first postnatal week, the current-voltage relationship of all encountered MS neurons was linear over a wide range of membrane potentials above and below RMP. Through the second postnatal week, the proportion of neurons displaying inward rectification in the hyperpolarized range increased steadily and after P15, all recorded MS neurons displayed significant inward rectification. At all ages, inward rectification was blocked by extracellular cesium and tetra-ethyl ammonium and was not changed by 4-aminopyridine; this shows that inward rectification was mediated by the same currents in young and mature MS neurons. MS neurons fired single and repetitive Na+/K+ action potentials as early as P1. Spike threshold and amplitude remained constant throughout development in contrast to spike duration, which decreased significantly over the same period. Depolarizing current pulses from rest showed that immature MS neurons fired action potentials more easily than their older counterparts. Taken together, the results from the present study suggest that young and adult nAcb MS neurons integrate excitatory synaptic inputs differently because of differences in their membrane and firing properties. These findings provide important insights into signal processing within nAcb during this critical period of development.
Analysis of Single KATPChannels in Mammalian Dentate Gyrus Granule Cells
Authors: Pelletier Marc R. , Pahapill Peter A. , Pennefather Peter S. , Carlen Peter L.
Published: December 2017

ATP-sensitive potassium (KATP) channels are heteromultimer complexes of subunits from members of the inwardly rectifying K+channel and the ATP-binding cassette protein superfamilies. KATPchannels couple metabolic state to membrane excitability, are distributed widely, and participate in a variety of physiological functions. Understood best in pancreatic β cells, where their activation inhibits insulin release, KATPchannels have been implicated also in postischemia cardio- and neuroprotection. The dentate gyrus (DG) is a brain region with a high density of KATPchannels and is relatively resistant to ischemia/reperfusion-induced cell death. Therefore we were interested in describing the characteristics of single KATPchannels in DG granule cells. We recorded single KATPchannels in 59/105 cell-attached patches from DG granule cells in acutely prepared hippocampal slices. Single-channel openings had an EKclose to 0 mV (symmetrical K+) and were organized in bursts with a duration of 19.3 ± 1.6 (SE) ms and a frequency of 3.5 ± 0.8 Hz, a unitary slope conductance of 27 pS, and a low, voltage-independent, probability of opening ( Popen, 0.04 ± 0.01). Open and closed dwell-time histograms were fitted best with one (τopen= 1.3 ± 0.2 ms) and the sum of two (τclosed,fast= 2.6 ± 0.9 ms, τclosed,slow= 302.7 ± 67.7 ms) exponentials, respectively, consistent with a kinetic model having at least a single open and two closed states. The Popenwas reduced ostensibly to zero by the sulfonylureas, glybenclamide (500 nM, 2/6; 10 μM,11/14 patches) and tolbutamide (20 μM, 4/6; 100 μM, 4/4 patches). The blocking dynamics for glybenclamide included transition to a subconductance state (43.3 ± 2.6% of control Iopen channel). Unlike glybenclamide, the blockade produced by tolbutamide was reversible. In 5/5 patches, application of diazoxide (100 μM) increased significantly Popen(0.12 ± 0.02), which was attributable to a twofold increase in the frequency of bursts (8.3 ± 2.0 Hz). Diazoxide was without effect on τopenand τclosed,fastbut decreased significantly τclosed,slow(24.4 ± 2.6 ms). We observed similar effects in 6/7 patches after exposure to hypoxia/hypoglycemia, which increased significantly Popen(0.09 ± 0.03) and the frequency of bursts (7.1 ± 1.7 Hz) and decreased significantly τclosed,slow(29.5 ± 1.8 ms). We have presented convergent evidence consistent with single KATPchannel activity in DG granule cells. The subunit composition of KATPchannels native to DG granule cells is not known; however, the characteristics of the channel activity we recorded are representative of Kir6.1/SUR1, SUR2B-based channels.
Cannabinoid and Kappa Opioid Receptors Reduce Potassium K Current via Activation of Gs Proteins in Cultured Hippocampal Neurons
Authors: Hampson Robert E. , Mu Jian , Deadwyler Sam A.
Published: December 2017

The current study showed that potassium K current ( I K), which is evoked at depolarizing potentials between −30 and +40 mV in cultured hippocampal neurons, was significantly reduced by exposure to the CB1 cannabinoid receptor agonist WIN 55,212-2 (WIN-2). WIN-2 (20–40 nM) produced an average 45% decrease in I K amplitude across all voltage steps, which was prevented by SR141716A, the CB1 receptor antagonist. The cannabinoid receptor has previously been shown to be Gi/o protein-linked to several cellular processes; however, the decrease in I Kwas unaffected by modulators of Gi/o proteins and agents that alter levels of protein kinase A. In contrast, CB1 receptor-mediated or direct activation of Gsproteins with cholera toxin (CTX) produced the same decrease in I K amplitude as WIN-2, and the latter was blocked in CTX-treated cells. Gs protein inhibition via GDPβS also eliminated the effects of WIN-2 on I K. Consistent with this outcome, activation of protein kinase C (PKC) by arachidonic acid produced similar effects to WIN-2 and CTX. Kappa opioid receptor agonists, which also reduce I K amplitude via Gs proteins, were compared with WIN-2 actions on I K. The kappa receptor agonist U50,488 reduced I K amplitude in the same manner as WIN-2, while the kappa receptor antagonist, nor-binaltorphimine, actually increased I K amplitude and significantly reduced the effect of co-administered WIN-2. The results indicate that CB1 and kappa receptor activation is additive with respect to I K amplitude, suggesting that CB1 and kappa receptors share a common Gs protein signaling pathway involving PKC.
Centrally Initiated Postural Adjustments in Parkinsonian Patients On and Off Levodopa
Authors: Frank J. S. , Horak F. B. , Nutt J.
Published: December 2017

This study investigates the effects of parkinsonism and dopamine replacement therapy (levodopa) on centrally initiated postural activity preceding rising onto the toes. The electromyographic (EMG) and force magnitude, scaling, sequencing, and postural stabilization were compared when rising-to-toes under two conditions, slow/low versus fast/high, for parkinsonian patients and elderly control subjects. Parkinsonian subjects were tested after withholding their levodopa medication for 12–16 h and again 1 h after taking their medication when parkinsonian signs were diminished. Parkinsonian subjects showed reduced magnitudes and delayed timing of the postural and voluntary components of the rise-to-toes task, as if they had difficulty turning off the postural, tibialis anterior (TIB) component and initiating the voluntary, gastrocnemius (GAS) component. Dopamine improved the relative timing, as well as the magnitude of both postural and voluntary components of rise-to-toes. Although the magnitude of dorsiflexion torque was smaller for parkinsonian subjectson and off than for healthy elderly controls, the parkinsonian subjects showed intact scaling of the magnitude of postural activity. Parkinsonian subjects do not perform the rise-to-toes task like normal subjects who are instructed to rise slowly; the relative timing of TIB and GAS activation was different even at comparable speeds of performance. Parkinsonian subjects, bothon and off, exhibited greater risk of falling than elderly control subjects when rising to toes. This increased risk of falling was reflected in a smaller safety margin between the peak center of mass (CoM) and peak center of pressure (CoP) during the task. The magnitude of mean postural dorsiflexion torque in the rise-to-toes task was highly correlated with a clinical rating scale of gait and balance, suggesting that force control is a critical factor influencing postural control in patients with Parkinson's disease.
Topographical and Physiological Characterization of Interneurons That Express Engrailed-1 in the Embryonic Chick Spinal Cord
Authors: Wenner Peter , O'Donovan Michael J. , Matise Michael P.
Published: December 2017

A number of homeodomain transcription factors have been implicated in controlling the differentiation of various types of neurons including spinal motoneurons. Some of these proteins are also expressed in spinal interneurons, but their function is unknown. Progress in understanding the role of transcription factors in interneuronal development has been slow because the synaptic connections of interneurons, which in part define their identity, are difficult to establish. Using whole cell recording in the isolated spinal cord of chick embryos, we assessed the synaptic connections of lumbosacral interneurons expressing the Engrailed-1 (En1) transcription factor. Specifically we established whether En1-expressing interneurons made direct connections with motoneurons and whether they constitute a single interneuron class. Cells were labeled with biocytin and subsequently processed for En1 immunoreactivity. Our findings indicate that the connections of En1-expressing cells with motoneurons and with sensory afferents were diverse, suggesting that the population was heterogeneous. In addition, the synaptic connections we tested were similar in interneurons that expressed the En1 protein and in many that did not. The majority of sampled En1 cells did, however, exhibit a direct synaptic connection to motoneurons that is likely to be GABAergic. Because our physiological methods underestimate the number of direct connections with motoneurons, it is possible that the great majority, perhaps all, En1-expressing cells make direct synaptic connections with motoneurons. Our results raise the possibility that En1 could be involved in interneuron-motoneuron connectivity but that its expression is not restricted to a distinct functional subclass of ventral interneuron. These findings constrain hypotheses about the role of En-1 in interneuron development and function.
Activity of Primate V1 Cortical Neurons During Blinks
Authors: Gawne Timothy J. , Martin Julie M.
Published: December 2017

Every time we blink our eyes, the image on the retina goes almost completely dark. And yet we hardly notice these interruptions, even though an external darkening is startling. Intuitively it would seem that if our perception is continuous, then the neuronal activity on which our perceptions are based should also be continuous. To explore this issue, we compared the responses of 63 supragranular V1 neurons recorded from two awake monkeys for four conditions: 1) constant stimulus, 2) during a reflex blink, 3) during a gap in the visual stimulus, and 4) during an external darkening when an electrooptical shutter occluded the entire scene. We show here that the activity of neurons in visual cortical area V1 is essentially shut off during a blink. In the 100-ms epoch starting 70 ms after the stimulus was interrupted, the firing rate was 27.2 ± 2.7 spikes/s (SE) for a constant stimulus, 8.2 ± 0.9 spikes/s for a reflex blink, 17.3 ± 1.9 spikes/s for a gap, and 12.7 ± 1.4 spikes/s for an external darkening. The responses during a blink are less than during an external darkening ( P < 0.05, t-test). However, many of these neurons responded with a transient burst of activity to the onset of an external darkening and not to a blink, suggesting that it is the suppression of this transient which causes us to ignore blinks. This is consistent with other studies where the presence of transient bursts of activity correlates with the perceived visibility of a stimulus.
Seizures Induce Simultaneous GABAergic and Glutamatergic Transmission in the Dentate Gyrus-CA3 System
Authors: Gutiérrez Rafael
Published: December 2017

Monosynaptic and polysynaptic responses of CA3 pyramidal cells (PC) to stimulation of the dentate gyrus (DG) are normally blocked by glutamate receptor antagonists (GluRAs). However, after kindled seizures, GluRAs block the monosynaptic excitatory postsynaptic potential (EPSP) and isolate a monosynaptic inhibitory postsynaptic potential (IPSP), suggesting that mossy fibers release GABA. However, kindling epilepsy induces neuronal sprouting, which can underlie this fast inhibitory response. To explore this possibility, the synaptic responses of PC to DG stimulation were analyzed in kindled epileptic rats, with and without seizures, and in nonepileptic rats, immediately after a single pentylenetetrazol (PTZ)-induced seizure, in which sprouting is unlikely to have occurred. Excitatory and inhibitory synaptic responses of PC to DG stimulation were blocked by GluRAs in control cells and in cells from kindled nonseizing rats, confirming that inhibitory potentials are disynaptically mediated. However, a fast IPSP could be evoked in kindled epileptic rats and in nonepileptic rats after a single PTZ-induced seizure. The same response was induced after rekindling the epileptic nonseizing rats. This IPSP has an onset latency that parallels that of the control EPSP and is not altered under low Ca2+ medium or halothane perfusion. In addition, it was reversibly depressed byl(+)-2-amino-4-phosphonobutyric acid (l-AP4), which is known to inhibit transmitter release from mossy fibers. These results demonstrate that seizures, and not the synaptic rearrangement due to an underlying epileptic state, induce the emergence of fast inhibition in the DG-CA3 system, and suggest that the mossy fibers underlie this plastic change.
Agatoxin-IVA-Sensitive Calcium Channels Mediate the Presynaptic and Postsynaptic Nicotinic Activation of Cardiac Vagal Neurons
Authors: Wang Jijiang , Irnaten Mustapha , Mendelowitz David
Published: December 2017

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency in cardiac vagal neurons. These responses were inhibited by the nonselective voltage-dependent calcium channel blocker Cd (100 μM). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 μM), an antagonist of L-type calcium channels, inhibited the increase in mini amplitude and frequency but did not block the ligand gated inward current. The N- and Q-type voltage-dependent calcium channel antagonists conotoxin GVIA (1 μM) and conotoxin MVIIC (5 μM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardiac vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive and possibly L-type voltage-dependent calcium channels. The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels.
Pattern Generation for Walking and Searching Movements of a Stick Insect Leg. I. Coordination of Motor Activity
Authors: Fischer Hanno , Schmidt Joachim , Haas Roman , Büschges Ansgar
Published: December 2017

During walking, the six legs of a stick insect can be coordinated in different temporal sequences or gaits. Leg coordination in each gait is controlled and stabilized by coordinating mechanisms that affect the action of the segmental neuronal networks for walking pattern generation. At present, the motor program for single walking legs in the absence of movement-related coordinating intersegmental influences from the other legs is not known. This knowledge is a prerequisite for the investigation of the segmental neuronal mechanisms that control the movements of a leg and to study the effects of intersegmental coordinating input. A stick insect single middle leg walking preparation has been established that is able to actively perform walking movements on a treadband. The walking pattern showed a clear division into stance and swing phases and, in the absence of ground contact, the leg performed searching movements. We describe the activity patterns of the leg muscles and motoneurons supplying the coxa-trochanteral joint, the femur-tibial joint, and the tarsal leg joints of the middle leg during both walking and searching movements. Furthermore we describe the temporal coordination between them. During walking movements, the coupling between the leg joints was phase-constant; in contrast during searching movements, the coupling between the leg joints was dependent on cycle period. The motor pattern of the single leg generated during walking exhibits similarities with the motor pattern generated during a tripod gait in an intact animal. The generation of walking movements also drives the activity of thoraco-coxal motoneurons of the deafferented and de-efferented thoraco-coxal leg joint in a phase-locked manner, with protractor motoneurons being active during swing and retractor motoneurons being active during stance. These results show that for the single middle leg, a basic walking motor pattern is generated sharing similarities with the tripod gait and that the influence of the motor pattern generated in the distal leg joints is sufficient for driving the activity of coxal motoneurons so an overall motor pattern resembling forward walking is generated.
Electrotonic Structure of Motoneurons in the Spinal Cord of the Turtle: Inferences for the Mechanisms of Bistability
Authors: Svirskis Gytis , Gutman Aron , Hounsgaard Jørn
Published: December 2017

Understanding how voltage-regulated channels and synaptic membrane conductances contribute to response properties of neurons requires reliable knowledge of the electrotonic structure of dendritic trees. A novel method based on weak DC field stimulation and the classical method based on current injection were used to obtain two independent estimates of the electrotonic structure of motoneurons in an in vitro preparation of the turtle spinal cord. DC field stimulation was also used to ensure that the passive membrane properties near the resting membrane potential were homogeneous. In two cells, the difference in electrotonic lengths estimated with the two methods in the same cell was 6 and 9%. The majority of dendritic branches terminated at a distance of 1 electrotonic unit from the recording site. The longest branches reached 2 λ. In the third cell, the difference was 36%, demonstrating the need to use both methods, field stimulation and current injection, for reliable measurements of the electrotonical structure. Models of the reconstructed cells endowed with voltage-dependent conductances were used to explore generation mechanisms for the experimentally observed hysteresis in input current-voltage relation of bistable motoneurons. The results of modeling suggest that only some dendrites need to possess L-type calcium current to explain the hysteresis observed experimentally and that dendritic branches with different electrotonical lengths can be bistable. Independent bistable behavior in individual dendritic branches can make motoneurons complex processing units.
CB1 Cannabinoid Receptor Inhibits Synaptic Release of Glutamate in Rat Dorsolateral Striatum
Authors: Gerdeman Gregory , Lovinger David M.
Published: December 2017

CB1 cannabinoid receptors in the neostriatum mediate profound motor deficits induced when cannabinoid drugs are administered to rodents. Because the CB1 receptor has been shown to inhibit neurotransmitter release in various brain areas, we investigated the effects of CB1 activation on glutamatergic synaptic transmission in the dorsolateral striatum of the rat where the CB1 receptor is highly expressed. We performed whole cell voltage-clamp experiments in striatal brain slices and applied the CB1 agonists HU-210 or WIN 55,212–2 during measurement of synaptic transmission. Excitatory postsynaptic currents (EPSCs), evoked by electrical stimulation of afferent fibers, were significantly reduced in a dose-dependent manner by CB1 agonist application. EPSC inhibition was accompanied by an increase in two separate indices of presynaptic release, the paired-pulse response ratio and the coefficient of variation, suggesting a decrease in neurotransmitter release. These effects were prevented by application of the CB1 antagonist SR141716A. When Sr2+ was substituted for Ca2+ in the extracellular solution, application of HU-210 (1 μM) significantly reduced the frequency, but not amplitude, of evoked, asynchronous quantal release events. Spontaneous release events were similarly decreased in frequency with no change in amplitude. These findings further support the interpretation that CB1 activation leads to a decrease of glutamate release from afferent terminals in the striatum. These results reveal a novel potential role for cannabinoids in regulating striatal function and thus basal ganglia output and may suggest CB1-targeted drugs as potential therapeutic agents in the treatment of Parkinson's disease and other basal ganglia disorders.
Subthreshold Inactivation of Na+ and K+Channels Supports Activity-Dependent Enhancement of Back-Propagating Action Potentials in Hippocampal CA1
Authors: Pan Enhui , Colbert Costa M.
Published: December 2017

Back-propagating action potentials in CA1 pyramidal neurons may provide the postsynaptic dendritic depolarization necessary for the induction of long-term synaptic plasticity. The amplitudes of back-propagating action potentials are not all or none but are limited in amplitude by dendritic A-type K+ channels. Previous studies of back-propagating action potentials have suggested that prior depolarization of the dendritic membrane reduces A-type channel availability through inactivation, resulting in an enhanced, or boosted, dendritic action potential. However, inactivation kinetics in the subthreshold potential range have not been directly measured. Furthermore, the corresponding rates of Na+channel inactivation with depolarization have not been considered. Here we report in cell-attached patches (150–220 μm from the soma, 32°C) that at 20-mV positive to rest, A-type K+channels inactivated with a single exponential time constant of 6 ms, whereas Na+ channels inactivated with a time constant of 37 ms. The ratio of available Na+ to K+ current increased as the duration of the depolarization increased. Thus the subthreshold properties of Na+ and A-type K+ channels provide a mechanism by which information about the level of synaptic activity may be encoded in the amplitude of back-propagating action potentials.
Immature Neocortical Neurons Exist as Extensive Syncitial Networks Linked by Dendrodendritic Electrical Connections
Authors: Peinado Alejandro
Published: December 2017

The properties of immature cortex that may enable it to exhibit large-scale wavelike activity during a brief critical developmental period were investigated by imaging neuronal calcium signals in neonatal cortical slices under conditions of artificially enhanced excitability, conditions that produce a more frequent and robust version of the naturally occurring waves. Using pharmacological manipulation to probe the underlying mechanisms, I show that waves can propagate effectively when excitatory synaptic transmission is blocked. In contrast, propagation is very sensitive to reductions in gap junctional communication. In the barrel field cortex wave propagation is affected by the underlying cytoarchitecture in a way that is consistent with a role for dendrodendritic gap junctions. The ability of cortex to sustain wave activity ends around postnatal day 12,precisely when a major reduction in neuronal gap junctions takes place in cortex. These results suggest that in immature cortex gap junctions link neurons into extensive networks that may allow electrical activity to spread over long distances.