bluuebunny/crossref_metadata_2025 huggingface dataset:
Interneurons in Area CA1 Stratum Radiatum and Stratum Oriens Remain Functionally Connected to Excitatory Synaptic Input in Chronically Epileptic Animals
Authors: Rempe D. A. , Bertram E. H. , Williamson J. M. , Lothman E. W.
Published: December 2017

Rempe, D. A., E. H. Bertram, J. M. Williamson, and E. W. Lothman. Interneurons in area CA1 stratum radiatum and stratum oriens remain functionally connected to excitatory synaptic input in chronically epileptic animals. J. Neurophysiol. 78: 1504–1515, 1997. Past work has demonstrated a reduction of stimulus-evoked inhibitory input to hippocampal CA1 pyramidal cells in chronic models of temporal lobe epilepsy (TLE). It has been postulated that this reduction in inhibition results from impaired excitation of inhibitory interneurons. In this report, we evaluate the connectivity of area CA1 interneurons to their excitatory afferents in hippocampal-parahippocampal slices obtained from a rat model of chronic TLE. Rats were made chronically epileptic by a period of continuous electrical stimulation of the hippocampus, which establishes an acute condition of self-sustained limbic status epilepticus (SSLSE). This period of SSLSE is followed by a development of chronic recurrent spontaneous limbic seizures that are associated with chronic neuropathological changes reminiscent of those encountered in human TLE. Under visual control, whole cell patch-clamp recordings of interneurons and pyramidal cells were obtained in area CA1 of slices taken from adult, chronically epileptic post-SSLSE rats. Neurons were activated by means of electrodes positioned in stratum radiatum. Intrinsic membrane properties, including resting membrane potential, action potential (AP) threshold, AP half-height width, and membrane impedance, were unchanged in interneurons from chronically epileptic (post-SSLSE) tissue compared with control tissue. Single stimuli delivered to stratum radiatum evoked depolarizing excitatory postsynaptic potentials and APs in interneurons, whereas paired-pulse stimulation evoked facilitation of the postsynaptic current (PSC) in both control and post-SSLSE tissue. No differences between interneurons in control versus post-SSLSE tissue could be found with respect to the mean stimulus intensity or mean stimulus duration needed to evoke an AP. A multiple linear regression analysis over a range of stimulus intensities demonstrated that a greater number of APs could be evoked in interneurons in post-SSLSE tissue compared with control tissue. Spontaneous PSCs were observed in area CA1 interneurons in both control and post-SSLSE tissue and were markedly attenuated by glutamatergic antagonists. In conclusion, our data suggest that stimulus-evoked and spontaneous excitatory synaptic input to area CA1 interneurons remains functional in an animal model of chronic temporal lobe epilepsy. These findings suggest, therefore, that the apparent decrease of polysynaptic inhibitory PSPs in CA1 pyramidal cells in epileptic tissue is not due to a deficit in excitatory transmission from Schaffer collaterals to interneurons in stratum radiatum and straum oriens.
Properties of Individual Embryonic Primary Afferents and Their Spinal Projections in the Rat
Authors: Mirnics Károly , Koerber H. Richard
Published: December 2017

Mirnics, Károly and H. Richard Koerber. Properties of individual embryonic primary afferents and their spinal projections in the rat. J. Neurophysiol. 78: 1590–1600, 1997. Embryonic (E19-E20) and early postnatal (P2) spinal cords with intact saphenous and sciatic nerves were isolated and placed in aerated artificial cerebral spinal fluid (CSF). Intracellular recordings were made from cells in the L2–L6 dorsal root ganglia using microelectrodes filled with 3 M potassium acetate or 5% neurobiotin (NB) in 1 M potassium acetate. Several physiological properties of adequately impaled cells were measured, including peripheral conduction velocity, action potential (AP) amplitude and duration, duration of afterhyperpolarization (AHP), input impedance, rheobase, presence of inward rectifying current, and maximum somal firing frequency. The extent to which these properties are correlated also was determined. One cell per ganglion was injected with NB. Stained somata and their central projections in the spinal cord were visualized in serial 50 μm sections. Cell size was determined and the central morphology of the central projections examined. Although some fibers were in the process of growing into the spinal cord, others had established projections over several millimeters in the dorsal columns. Although most of these fibers supported projections in the gray matter, 22% only maintained fibers in the dorsal columns. Fibers with projections in the dorsal horn exhibited three types of morphology: projections confined to the superficial dorsal horn (laminae I, II); terminals confined to laminae III-V; and projections spanning laminae II-V. In addition, some embryonic fibers maintained projections to the dorsal horn that extended over five lumbar segments. Somal APs could be divided into two groups: broad spikes with inflections on their falling phase and narrow spikes without inflections. On average, cells with broad spikes (BS) had the following characteristics: slower peripheral conduction velocity, larger amplitude, higher rheobase and input impedance, longer AHP duration, and lower maximum firing frequency. There were significant correlations between conduction velocity and several of the physiological properties. Conduction velocity was negatively correlated with AP duration, rheobase, and input impedance and positively correlated with maximum firing frequency. Comparisons between spike shape and central morphology revealed that cells lacking collaterals in the gray matter and those with projections in the superficial dorsal horn always had broad somal spikes with inflections. Those with projections confined to laminae III-V always had narrow somal spikes (NS).
Tangential Torque Effects on the Control of Grip Forces When Holding Objects With a Precision Grip
Authors: Kinoshita Hiroshi , Bäckström Lars , Flanagan J. Randall , Johansson Roland S.
Published: December 2017

Kinoshita, Hiroshi, Lars Bäckström, J. Randall Flanagan, and Roland S. Johansson. Tangential torque effects on the control of grip forces when holding objects with a precision grip. J. Neurophysiol. 78: 1619–1630, 1997. When we manipulate small objects, our fingertips are generally subjected to tangential torques about the axis normal to the grasp surface in addition to linear forces tangential to the grasp surface. Tangential torques can arise because the normal force is distributed across the contact area rather than focused at a point. We investigated the effects of tangential torques and tangential forces on the minimum normal forces required to prevent slips (slip force) and on the normal forces actually employed by subjects to hold an object in a stationary position with the use of the tips of the index finger and thumb. By changing the location of the object's center of gravity in relation to the grasp surface, various levels of tangential torque (0–50 N⋅mm) were created while the subject counteracted object rotation. Tangential force (0–3.4 N) was varied by changing the weight of the object. The flat grasp surfaces were covered with rayon, suede, or sandpaper, providing differences in friction in relation to the skin. Under zero tangential force, both the employed normal force and the slip force increased in proportion to tangential torque with a slope that reflected the current frictional condition. Likewise, with pure tangential force, these forces increased in proportion to tangential force. The effects of combined tangential torques and tangential forces on the slip force were primarily additive, but there was a significant interaction of these variables. Specifically, the increase in slip force for a given increment in torque decreases as a function of tangential force. A mathematical model was developed that successfully predicted slip force from tangential torque, tangential force, and an estimate of coefficient of static friction in the digit-surface interface. The effects of combined tangential torques and forces on the employed normal force showed the same pattern as the effects on the slip force. The safety margin against frictional slips, measured as the difference between the employed normal force and the slip force, was relatively small and constant across all tangential force and torque levels except at small torques (<10 N⋅mm). There was no difference in safety margin between the digits. In conclusion, tangential torque strongly influences the normal force required for grasp stability. When controlling normal force, people take into account, in a precise fashion, the slip force reflecting both tangential force and tangential torque and their interaction as well as the current frictional condition in the object-digit interface.
Synaptic Activation of Ca2+ Action Potentials in Immature Rat Cerebellar Granule Cells In Situ
Authors: D'Angelo Egidio , De Filippi Giovanna , Rossi Paola , Taglietti Vanni
Published: December 2017

D'Angelo, Egidio, Giovanna De Filippi, Paola Rossi, and Vanni Taglietti. Synaptic activation of Ca2+ action potentials in immature rat cerebellar granule cells in situ. J. Neurophysiol. 78: 1631–1642, 1997. Although numerous Ca2+ channels have been identified in cerebellar granule cells, their role in regulating excitability remained unclear. We therefore investigated the excitable response in granule cells using whole cell patch-clamp recordings in acute rat cerebellar slices throughout the time of development (P4–P21, n = 183), with the aim of identifying the role of Ca2+ channels and their activation mechanism. After depolarizing current injection, 46% of granule cells showed Ca2+ action potentials, whereas repetitive Na+ spikes were observed in an increasing proportion of granule cells from P4 to P21. Because Ca2+ action potentials were no longer observed after P21, they characterized an immature granule cell functional stage. Ca2+ action potentials consisted of an intermediate-threshold spike (ITS) activating at −60/−50 mV and sensitive to voltage inactivation and of a high-threshold spike (HTS), activating at above −30 mV and resistant to voltage inactivation. Both ITS and HTS comprised transient and protracted Ca2+ channel-dependent depolarizations. The Ca2+ action potentials could be activated synaptically by excitatory postsynaptic potentials, which were significantly slower and had a proportionately greater N-methyl-d-aspartate (NMDA) receptor-mediated component than those recorded in cells with fast repetitive Na+ spikes. The NMDA receptor current, by providing a sustained and regenerative current injection, was critical for activating the ITS, which was not self-regenerative. Moreover, NMDA receptors determined temporal summation of impulses during repetitive mossy fiber transmission, raising membrane potential into the range required for generating protracted Ca2+ channel-dependent depolarizations. The nature of Ca2+ action potentials was considered further using selective ion channel blockers. N-, L-, and P-type Ca2+ channels generated protracted depolarizations, whereas the ITS and HTS transient phase was generated by putative R-type channels (RITS and RHTS, respectively). RHTS channels had a higher activation threshold and were more resistant to voltage inactivation than RITS channels. At a mature stage, most of the Ca2+-dependent effects depended on the N-type current, which promoted spike repolarization and regulated the Na+-dependent discharge frequency. These observations relate Ca2+ channel types with specific neuronal excitable properties and developmental states in situ. Synaptic NMDA receptor-dependent activation of Ca2+ action potentials provides a sophisticated mechanism for Ca2+ signaling, which might be involved in granule cell development and plasticity.
Delayed Signal Propagation via CA2 in Rat Hippocampal Slices Revealed by Optical Recording
Authors: Sekino Yuko , Obata Kunihiko , Tanifuji Manabu , Mizuno Makoto , Murayama Jin
Published: December 2017

Sekino, Yuko, Kunihiko Obata, Manabu Tanifuji, Makoto Mizuno, and Jin Murayama. Delayed signal propagation via CA2 in rat hippocampal slices revealed by optical recording. J. Neurophysiol. 78: 1662–1668, 1997. Signal propagation from mossy fibers to CA1 neurons was investigated in rat hippocampal slices by a combination of electrical and optical recordings. The slices were prepared by oblique sectioning of the middle part of the hippocampus to preserve fiber connections. The mossy fibers were stimulated to induce population spikes (PSs) and excitatory postsynaptic potentials in the middle part of the CA1 region. Latencies of maximal PSs in CA1 varied widely among slices; they ranged from 7 to 13.5 ms, with two maxima at 9 and 11.5 ms. The fastest PSs probably are evoked by the Schaffer collaterals that connect the CA3 and CA1 regions in the well-known trisynaptic circuit. However, the slower PSs suggest the existence of additional delayed inputs. To determine the source of the delayed input, slices were stained with a voltage-sensitive dye, RH482, and the optical signals relevant to membrane potential changes were detected by a high-resolution optical imaging system. Optical recording of responses to mossy fiber stimulation indicated two distinct types of signal propagation from CA3 to CA1. In preparations evincing the fast type of propagation, signals spread to CA1 within 7.2 ms after the mossy fiber stimulation. During such propagation, activity flowed directly from CA3 to the stratum radiatum of CA1. Other preparations illustrated slow signal propagation, in which optical signals were generated in CA2 before spreading to CA1. During such slow signal transmission, activity persisted in CA2 and its surrounding area for 3 ms before propagating to the strata radiatum and oriens in CA1. In such cases, CA1 activity was detected within 10.8 ms of mossy fiber stimulation. In some slices, a mixture of the fast and slow propagation patterns was observed, indicating that these two transmission modes can coexist. Our data reveal that CA2 neurons can transmit delayed excitatory signals to CA1 neurons. We therefore conclude that consideration of electrical signal propagation through the hippocampus should include flow through the CA2 region in addition to the traditional dentate gyrus–CA3–CA1 trisynaptic circuit.
Two Conductances Mediate Thyrotropin-Releasing-Hormone-Induced Depolarization of Neonatal Rat Spinal Preganglionic and Lateral Horn Neurons
Authors: Kolaj Miloslav , Shefchyk Susan J. , Renaud Leo P.
Published: December 2017

Kolaj, Miloslav, Susan J. Shefchyk, and Leo P. Renaud. Two conductances mediate thyrotropin-releasing-hormone-induced depolarization of neonatal rat spinal preganglionic and lateral horn neurons. J. Neurophysiol. 78: 1726–1729, 1997. Thyrotropin-releasing hormone (TRH) has been recognized as a neuromodulator in several CNS regions, including the thoracolumbar spinal cord where an influence on cardiovascular autonomic function has been proposed. To identify the cellular mechanisms involved in the latter, whole cell patch-clamp recordings were obtained from 52 thoracolumbar lateral horn cells, including 17 sympathetic preganglionic neurons (SPNs), in spinal cord slices from neonatal rat (11–21 days). Under current clamp, bath applications of TRH (1–20 μM) induced a slowly rising and prolonged membrane depolarization in eight of nine cells tested. Under voltage clamp (holding potential −65 mV), 33 of 37 tested cells displayed a TRH-induced, tetrodotoxin-resistant inward current that was associated with either a reduction or an increase in membrane ion conductances. Current-voltage ( I-V) relationships in 28 cells suggested two conductances. In 9 cells the current reversed at about −107 mV; in 10 cells the I-V lines remained parallel, whereas in 9 cells the current reversed at around −40 mV. In three of three cells, addition of 2 mM barium was associated with an inward current, and the TRH-induced inward current was also suppressed, suggesting the presence of a resting barium- and TRH-sensitive potassium conductance. A residual barium-insensitive conductance was seen to reverse near −40 mV. Intracellular dialysis with guanosine 5′- o-(3-thiotriphosphate) significantly enhanced the duration of the TRH effect, indicating that G protein activation participates in the TRH response. These observations not only reveal a direct, G-protein-mediated depolarizing action of TRH on neonatal rat SPNs and lateral horn cells but also imply that two separate conductances may be involved in the TRH responses in some neurons.
Dorsal Column But Not Lateral Column Transection Prevents Down-Conditioning of H Reflex in Rats
Authors: Chen Xiang Yang , Wolpaw Jonathan R.
Published: December 2017

Chen, Xiang Yang and Jonathan R. Wolpaw. Dorsal column but not lateral column transection prevents down-conditioning of H reflex in rats. J. Neurophysiol. 78: 1730–1734, 1997. Operant conditioning of the H reflex, the electrical analogue of the spinal stretch reflex, in freely moving rats is a relatively simple model for studying long-term supraspinal control over spinal cord function. Motivated by food reward, rats can gradually increase or decrease the soleus H reflex. This study is the first effort to determine which spinal cord pathways convey the descending influence from supraspinal structures that changes the H reflex. In anesthetized Sprague-Dawley rats, the entire dorsal column (DC), which includes the main corticospinal tract, or the right lateral column (LC) was transected by electrocautery. Animals recovered quickly and the minimal transient effects of transection on the right soleus H reflex disappeared within 16 days. Beginning at least 18 days after transection, 12 rats were exposed to the HRdown-conditioning mode, in which reward was given when the H reflex of the right soleus muscle was below a criterion value. In seven LC rats exposed to the HRdown mode, the H reflex fell to 71 ± 8% (mean ± SE) of its initial value. In six of the seven, conditioning was successful (i.e., decrease to ≤80%). These results were comparable with those previously obtained from normal rats. In contrast, in five DC rats exposed to the HRdown mode, the H reflex at the end of exposure was 106 ± 12% of its initial value. In none of these rats was HRdown-conditioning successful. DC rats differed significantly from normal and LC rats in both final H reflex values and number successful. In five DC and three LC rats that continued under control conditions over 30–78 days, the H reflex at the end of the period was 98 ± 4% and 100 ± 8%, respectively, of its initial value, indicating that DC or LC transection itself did not lead to gradual increase or decrease in the H reflex. The results indicate that the DC, containing the main corticospinal tract, is essential for HRdown-conditioning, whereas the ipsilateral LC, containing the main rubrospinal, vestibulospinal, and reticulospinal tracts, is not essential. Combined with the known muscular specificity of conditioning, these results suggest that the main corticospinal tract is essential for HRdown-conditioning. The DC ascending tract might also be necessary. The respective roles of the DC descending and ascending tracts, and transection effects on HRup-conditioning and on the maintenance of both HRup- and HRdown-conditioning after they have occurred, remain to be defined.
Selective Cholinergic Modulation of Cortical GABAergic Cell Subtypes
Authors: Kawaguchi Yasuo
Published: December 2017

Kawaguchi, Yasuo. Selective cholinergic modulation of cortical GABAergic cell subtypes. J. Neurophysiol. 78: 1743–1747, 1997. Acetylcholine from the basal forebrain and γ-aminobutyric acid (GABA) from intracortical inhibitory interneurons exert strong influence on the cortical activity and may interact with each other. Cholinergic or muscarinic agonists indeed induced GABAergic postsynaptic currents in pyramidal cells by exciting inhibitory interneurons that have recently been classified into several distinct subtypes on the basis of the physiological, chemical, and morphological criteria. Cholinergic effects on GABAergic cell subtypes were investigated of rat frontal cortex by in vitro whole cell recording with intracellular staining in frontal cortex of young rats. GABAergic cell subtypes were identified physiologically by firing responses to depolarizing current pulses and immunohistochemically as containing parvalbumin, somatostatin, vasoactive intestinal polypeptide (VIP), or cholecystokinin (CCK). Carbachol (10 μM) or (+)-muscarine (3 μM) affected the activities of peptide-containing GABAergic cells with regular- or burst-spiking characteristics, but not of GABAergic cells with fast-spiking characteristics containing the calcium-binding protein parvalbumin orGABAergic cells with late-spiking characteristics. Somatostatin- or VIP-immunoreactive cells were depolarized with spike firing. CCK-immunoreactive cells were affected heterogeneously by cholinergic agonists. Larger CCK cells were hyperpolarized, followed by a slow depolarization, whereas smaller CCK cells were only depolarized. These results suggest that the excitability of cortical GABAergic cell subtypes is differentially regulated by acetylcholine. Differences in cholinergic responses suggest a distinct functional role of each GABAergic cell subtype.
Attenuation of Preparatory Activity for Reaching Movements by a D1-Dopamine Antagonist in the Monkey Premotor Cortex
Authors: Sawaguchi T.
Published: December 2017

Sawaguchi, T. Attenuation of preparatory activity for reaching movements by a D1-dopamine antagonist in the monkey premotor cortex. J. Neurophysiol. 78: 1769–1774, 1997. To examine the role of dopamine receptors in the function of the premotor cortex (PM) for preparing for reaching movements, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied iontophoretically to neurons of the PM of monkeys that performed a delayed-reaching (DR) task with their arms. In the DR task, the monkey made a reaching movement to one of three target levers (left, upper, and right), which had been cued by a visuospatial stimulus before a delay period of 4 s. We focused on neurons ( n = 56) that showed a sustained increase in activity during the delay period (delay-period activity; i.e., “set-related” activity), because such activity is considered to play a central role in preparing for forelimb movements. Iontophoretic application of SCH23390 (usually with a current of 50 nA) significantly decreased the activity of most of these neurons ( n = 44/56, 79%), and delay-period activity was attenuated during its application. In contrast, application of sulpiride or SCH23388 (an inactive analogue of SCH23390), using the same current intensity, had no effect on most of the neurons tested with these drugs ( n = 31/33 and n = 21/23, respectively), despite the fact that their activity was decreased by SCH23390. Furthermore, for neurons that were affected by SCH23390, the percent decrease in delay-period activity was significantly greater than the percent change in background activity. In more than one-half of the neurons ( n = 26/44, 59%), background activity was either increased ( n = 10) or not affected ( n = 16) by SCH23390, even though it significantly attenuated delay-period activity. These findings suggest that the activation of D1-dopamine receptors plays a modulatory role in PM function in preparing for reaching movements.
Two Types of Actions of Norepinephrine on Identified Auditory Efferent Neurons in Rat Brain Stem Slices
Authors: Wang Xueyong , Robertson Donald
Published: December 2017

Wang, Xueyong and Donald Robertson. Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices. J. Neurophysiol. 78: 1800–1810, 1997. Whole cell voltage-clamp recordings were performed on auditory olivocochlear neurons in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of norepinephrine (NE; 1–10 μM) reversibly induced an inward current in 26 of 38 labeled neurons that were voltage clamped at −75 mV. This was responsible for the membrane depolarization to NE observed in current-clamp mode. The NE-induced inward current appeared to be more prominent at −55 mV than at −75 mV and reversed at around −100 mV. It was attenuated but not prevented by 20 mM tetraethylammonium, and it persisted when the perfusate contained 2 mM Cs+ or 100 μM Cd2+. However, the NE-induced inward current was attenuated to varying degrees in a zero-Ca2+ solution. Current-voltage plots revealed that NE caused a decrease in membrane K+ conductance. A suppression of voltage-gated Ca2+ currents by NE was also observed. The excitatory action of NE was blocked by the α-adrenoreceptor antagonist phentolamine. The α1-adrenoreceptor agonist phenylephrine had an effect similar to that of NE. In 6 of 38 labeled neurons, an inhibitory action of NE (1–10 μM) was observed that appeared to be due to an activation of an inwardly rectified K+ current, which caused hyperpolarization of resting membrane potentials in current-clamp mode. This inhibitory response was independent of external Ca2+ and was abolished by 2–5 mM Cs+ or 0.5 mM Ba2+ applied in the perfusate. The receptors involved in the inhibitory actions of NE are not clear. The effect was partially and reversibly blocked by propranolol (10 μM), a β-adrenoreceptor antagonist. However, isoprenaline (10 μM), a β-adrenoreceptor agonist, failed to induce any effect. On the other hand, the inhibitory effect was irreversibly blocked by pretreatment with phentolamine (5–10 μM). Phenylephrine (5–10 μM) had no effect.
Fast, Slow, and Steady-State Effects of Contralateral Acoustic Activation of the Medial Olivocochlear Efferent System in Awake Guinea Pigs: Action of Gentamicin
Authors: da Costa Deise Lima , Chibois Anne , Erre Jean-Paul , Blanchet Christophe , de Sauvage RENAUD CHARLET , Aran Jean-Marie
Published: December 2017

Lima da Costa, Deise, Anne Chibois, Jean-Paul Erre, Christophe Blanchet, Renaud Charlet de Sauvage, and Jean-Marie Aran. Fast, slow, and steady-state effects of contralateral acoustic activation of the medial olivocochlear efferent system in awake guinea pigs: action of gentamicin. J. Neurophysiol. 78: 1826–1836, 1997. The function of the medial olivocochlear efferent system was observed in awake guinea pigs by recording, in the absence of ipsilateral external acoustic stimulation, the ensemble background activity (EBA) of the VIIIth nerve from an electrode chronically implanted on the round window of one ear. The EBA was measured by calculating the power value of the round window signal in the 0.5- to 2.5-kHz band after digital or analog (active) filtering. This EBA was compared with and without the addition of a low-level broadband noise to the opposite ear. The contralateral broadband noise (CLBN, 55 dB SPL) induced, via the efferent system, a decrease (suppression) of this EBA. With the use of noise bursts of different durations, two components in this suppression could be observed. After the onset of a 1-s CLBN, the power value of the EBA decreased rapidly by 38.0 ± 4.2% (mean ± SD, n = 3), with a latency of <10 ms and a decay time constant of 13.1 ± 1.0 ms (fast effect). At the offset of the 1-s CLBN, EBA came back to prestimulation values with a similar latency and a time constant of 15.5 ± 2.9 ms. During longer CLBN stimulation (≥1 min), EBA presented, after the fast decrease, an additional, slower decrease of 15.6 ± 3.1%, with a delay of 9.8 ± 1.3 s and a decay time constant of 16.1 ± 5.0 s ( n = 12, slow effect), and then remained remarkably constant for as long as observed, i.e., >2 h (steady state). The average global suppression was thus up to 47.8 ± 5.8% of the basal, pre-CLBN-stimulation EBA value. At the offset of the CLBN, EBA returned to pre-CLBN level with fast and slow phases, with, for the slow phase, no delay and a time constant of 32.1 ± 8.1 s. Fast and slow changes in EBA power values were observed after a single injection of gentamicin (GM) at different doses (150, 200, and 250 mg/kg). At 150 and 200 mg/kg, GM progressively and reversibly blocked the rapid effect, but the slow component of the efferent medial suppression remained remarkably unchanged. However, at higher doses both the fast and slow suppressions were totally yet still reversibly blocked. These observations indicate that the medial olivocochlear efferent system exerts sustained influences on outer hair cells and that this effect develops in two different steps that may have different basic cellular mechanisms.
M4 Muscarinic Receptor Activation Modulates Calcium Channel Currents in Rat Intracardiac Neurons
Authors: Cuevas J. , Adams D. J.
Published: December 2017

Cuevas, J. and Adams, D. J. M4 muscarinic receptor activation modulates calcium channel currents in rat intracardiac neurons. J. Neurophysiol. 78: 1903–1912, 1997. Modulation of high-voltage–activated Ca2+ channels by muscarinic receptor agonists was investigated in isolated parasympathetic neurons of neonatal rat intracardiac ganglia using the amphotericin B perforated-patch whole cell recording configuration of the patch-clamp technique. Focal application of the muscarinic agonists acetylcholine (ACh), muscarine, and oxotremorine-M to the voltage-clamped soma membrane reversibly depressed peak Ca2+ channel current amplitude. The dose-reponse relationship obtained for ACh-induced inhibition of Ba2+ current ( I Ba) exhibited a half-maximal inhibition at 6 nM. Maximal inhibition of I Ba amplitude obtained with 100 μM ACh was ∼75% compared with control at +10 mV. Muscarinic agonist-induced attenuation of Ca2+ channel currents was inhibited by the muscarinic receptor antagonists pirenzepine (≤300 nM) and m4-toxin (≤100 nM), but not by AF-DX 116 (300 nM) or m1-toxin (60 nM). The dose-response relationship obtained for antagonism of muscarine-induced inhibition of I Ba by m4-toxin gave an IC50 of 11 nM. These results suggest that muscarinic agonist-induced inhibition of high-voltage–activated Ca2+ channels in rat intracardiac neurons is mediated by the M4 muscarinic receptor. M4 receptor activation shifted the voltage dependence and depressed maximal activation of Ca2+ channels but had no effect on the steady-state inactivation of Ca2+ channels. Peak Ca2+ channel tail current amplitude was reduced ≥30% at +90 mV in the presence of ACh, indicating a voltage-independent component to the muscarinicreceptor-mediated inhibition. Both dihydropyridine- and ω-conotoxin GVIA–sensitive and -insensitive Ca2+ channels were inhibited by ACh, suggesting that the M4 muscarinic receptor is coupled to multiple Ca2+ channel subtypes in these neurons. Inhibition of I Ba amplitude by muscarinic agonists was also observed after cell dialysis using the conventional whole cell recording configuration. However, internal perfusion of the cell with 100 μM guanosine 5′-O-(2-thiodiphosphate) trilithium salt (GDP-β-S) or incubation of the neurons in Pertussis toxin (PTX) abolished the modulation of I Ba by muscarinic receptor agonists, suggesting the involvement of a PTX-sensitive G-protein in the signal transduction pathway. Given that ACh is the principal neurotransmitter mediating vagal innervation of the heart, the presence of this inhibitory mechanism in postganglionic intracardiac neurons suggests that it may serve for negative feedback regulation.
Mitochondrial Regulation of Calcium in the Avian Cochlear Nucleus
Authors: Mostafapour Sam P. , Lachica Edward A. , Rubel Edwin W
Published: December 2017

Mostafapour, Sam P., Edward A. Lachica, and Edwin W Rubel. Mitochondrial regulation of calcium in the avian choclear nucleus. J. Neurophysiol. 78: 1928–1934, 1997. The role of mitochondria and the endoplasmic reticulum in buffering [Ca2+]iin response to imposed calcium loads in neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), was examined. Intracellular calcium concentrations were measured using fluorometric videomicroscopy. After depolarization with 125 mM KCl, NM neurons demonstrate an increase in [Ca2+]ithat returns to near-basal levels within 6 min. Addition of the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) dissipated the mitochondrial membrane potential, as evidenced by increased fluorescence when cells were loaded with rhodamine-123. Two micromolar CCCP had minimal effect on baseline [Ca2+]i. However, 2 or 10 μM CCCP interfered with the ability of NM cells to buffer [Ca2+]iin response to KCl depolarization without significantly affecting peak [Ca2+]i. Oligomycin also interfered with postdepolarization regulation of [Ca2+]i, but blocked late (7–8 min postdepolarization) increases in [Ca2+]icaused by CCCP. Thapsigargin had no effect on baseline, peak, or postdepolarization [Ca2+]iin NM cells. These results suggest that normal mitochondrial membrane potential and ATP synthesis play an important role in buffering [Ca2+]iin response to imposed calcium loads in NM neurons. Furthermore, the endoplasmic reticulum does not appear to play a significant role in either of these processes. Thus increases in mitochondrial number and function noted in NM cells after deafferentation may represent an adaptive response to an increased cytosolic calcium load.
NMDA-Independent LTP by Adenosine A2 Receptor-Mediated Postsynaptic AMPA Potentiation in Hippocampus
Authors: Kessey Kofi , Mogul David J.
Published: December 2017

Kessey, Kofi and David J. Mogul. NMDA-independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus. J. Neurophysiol. 78: 1965–1972, 1997. The role of adenosine A2 receptors in normal synaptic transmission and tetanus-induced long-term potentiation (LTP) was tested by stimulation of the Schaffer collateral pathway and recording of the field excitatory postsynaptic potential (EPSP) in the CA1 region of rat transverse hippocampal slices. Activation of adenosine A2 receptors with the A2 agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic transmission during low-frequency test pulses (0.033 Hz). Paired stimulation before and during DPMA exposure indicated no paired-pulse facilitation as a result of A2 activation, suggesting that enhancement was not a result of presynaptic modulation. DPMA enhanced the early phase α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the EPSP. In contrast, DPMA had no effect on the N-methyl-d-aspartate (NMDA) component isolated using low extracellular Mg2+ and the AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM), indicating that the effects of A2 activation on synaptic transmission were mediated by a postsynaptic enhancement of the AMPA response. Activation of adenosine A2 receptors during a brief tetanus (100 Hz, 1 s) increased the level of LTP by 36% over that seen in response to a tetanus under control conditions. DPMA exposure after prior induction of LTP showed no additional potentiation, indicating that the mechanisms that contribute to both types of increases in synaptic transmission share a common mechanism. A slow onset NMDA-independent LTP could be induced by application of a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 μM). Blockade of L-type Ca channels with nifedipine (10 μM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP could be induced after prior saturation of NMDA-dependent LTP via multiple tetani spaced 10 min apart, indicating that both forms of LTP are eventually convergent on a common mechanism, presumably the postsynaptic AMPA receptor response. Because extracellular adenosine levels are modulated by cellular activity throughout the brain and because adenosine receptor activation can markedly alter levels of synaptic transmission independent of NMDA receptors, adenosine may play an important and complex role as a modulator of synaptic transmission in the brain.
Calcium-Activated Cation Nonselective Current Contributes to the Fast Afterdepolarization in Rat Prefrontal Cortex Neurons
Authors: Haj-Dahmane Samir , Andrade Rodrigo
Published: December 2017

Haj-Dahmane, Samir and Rodrigo Andrade. Calcium-activated cation nonselective current contributes to the fast afterdepolarization in rat prefrontal cortex neurons. J. Neurophysiol. 78: 1983–1989, 1997. Pyramidal cells of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) following an action potential. This ADP is blocked by replacing extracellular calcium with magnesium, by the application of the calcium-channel blocker cadmium, and by buffering intracellular calcium at near physiological levels. Thus this fast ADP appears mediated by a calcium-activated current. A prominent ADP is also observed following a calcium spike recorded in the presence of tetrodotoxin. The current underlying this ADP was recorded using a hybrid current-voltage protocol. A strong ADP could be observed in the presence of potassium channel blockers as well as at ECl. Furthermore, the current underlying the ADP increased with hyperpolarization in the subthreshold range and displayed an extrapolated reversal potential near +30 mV. Reducing the ratio of extracellular to intracellular sodium inhibited the current underlying the ADP and caused a hyperpolarizing shift in its reversal potential. We conclude that these cells express a calcium-activated cation nonselective current whose activation contributes to the generation of the fADP. This current could play an important role in determining the firing properties of pyramidal cells in cortex.
Cholecystokinin Activates CCKB-Receptor–Mediated Ca-Signaling in Hippocampal Astrocytes
Authors: Müller Wolfgang , Heinemann Uwe , Berlin Karin
Published: December 2017

Müller, Wolfgang, Uwe Heinemann, and Karin Berlin. Cholecystokinin activates CCKB-receptor–mediated Ca-signaling in hippocampal astrocytes. J. Neurophysiol. 78: 1997–2001, 1997. Cholecystokinin-8S (CCK-8S) is the most abundant neuropeptide in the mammalian cortex and the limbic system; however, its physiological functions remained largely obscure. We studied effects of CCK on astrocytic Ca signaling, which has met considerable interest as a second messenger in astrocytic-neuronal signaling, by digital ratio-imaging of Fura-2/AM loaded rat and mouse hippocampal astrocytes in dissociated culture. Superfusion of CCK-8S (5–50 nM for 2 min) evoked repetitive Ca increases of several hundred nanomolar in a subpopulation of astrocytes. Mouse astrocytes appeared to be more responsive to CCK than rat cells with respect to the fraction of cells responding as well as to the amplitudes of Ca increases. The Ca responses persisted in the absence of extracellular Ca, indicating that release of Ca from intracellular stores is the primary source of these Ca increases. The CCK-8S–induced Ca increases were blocked by the CCKB receptor antagonist PD135158 (100 nM) but not by the CCKA antagonist lorglumide (100 nM). We surmise that astrocytes might be a major primary target for CCK in the CNS.
Processing of Color- and Noncolor-Coded Signals in the Gourami Retina. I. Horizontal Cells
Authors: Sakai Hiroko M. , Machuca Hildred , Naka Ken-Ichi
Published: December 2017

Sakai, Hiroko M., Hildred Machuca, and Ken-Ichi Naka. Processing of color- and noncolor-coded signals in the gourami retina. I. Horizontal cells. J. Neurophysiol. 78: 2002–2017, 1997. There are two types of horizontal cells, the luminosity and the chromaticity cells, in the retina of the kissing gourami, Helostoma rudolfi. Luminosity cells occupy the outermost layer proximal to the receptor terminals, whereas chromaticity cells form a layer proximal to the layer of luminosity cells. Neither type of cell has axons. Responses were evoked by light from red and green light-emitting diodes. The two stimuli were modulated either by a pulsatile or a white-noise signal. The luminosity cell always produced a hyperpolarizing response. The chromaticity cell produced a hyperpolarizing response when stimulated by only one color. However, in the presence of a steady or modulated green input, a red stimulus produced a depolarizing response. Such chromaticity cells were similar to the (spectral) biphasic chromaticity horizontal cells observed in other retinae. The depolarizing phase of the red response was produced by the balance of intensity of the two inputs, red and green. We used white-noise methodology to identify the dynamics of the horizontal cell's modulation response by taking advantage of the fact that a Wiener kernel is a measure of a cell's incremental sensitivity, which includes its response dynamics. Under all conditions, a steady state modulation response by both luminosity and chromaticity cells always was related linearly to the input modulation. The average mean square error (MSE) of the model predicted by the first-order kernel was ∼8% for both luminosity ( n = 116) and chromaticity ( n = 23) cells. In some cases, the MSE was a few percent even when the peak-to-peak response amplitude was nearly 30 mV. The ratio of inputs from red and green cones to both types of horizontal cells was variable; the major input for luminosity cells came from red cones, whereas the major input for chromaticity cells came from green cones. First-order kernels generated by the major input were robust in terms of waveform in the sense that the waveform remained unchanged whether or not there was a steady or modulated illumination by the opposing color. The results reported here do not address the question of the neural circuitry that generates horizontal cell responses, in particular, the depolarizing response. However, whatever that circuitry might be, the high degree of linearity of the modulation response by both types of cell under various stimulus conditions imposes restrictions on the performance of any proposed model as well as on mechanisms that underlie the generation of the horizontal cell response.
Activity Linked to Externally Cued Saccades in Single Units Recorded From Hippocampal, Parahippocampal, and Inferotemporal Areas of Macaques
Authors: Sobotka Stanislaw , Nowicka Anna , Ringo James L.
Published: December 2017

Sobotka, Stanislaw, Anna Nowicka, and James L. Ringo. Activity linked to externally cued saccades in single units recorded from hippocampal, parahippocampal, and inferotemporal areas of macaques. J. Neurophysiol. 78: 2156–2163, 1997. We studied whether target-directed, externally commanded saccadic eye movements (saccades) induced activity in single units in inferotemporal cortex, the hippocampal formation, and parahippocampal gyrus. The monkeys first were required to fix their gaze on a small cross presented to the left or right of center on the monitor screen. The cross was extinguished, and a random 600–1,000 ms thereafter, a small dot was presented for 200 ms. The dot was located either 10° above, below, right, or left of the position on which the fixation cross had been. The monkey made a saccadic eye movement to this dot (in darkness). The neuronal activity around this goal-directed saccade was analyzed. In addition, control conditions were imposed systematically in which similar dots were presented, but the monkey's task was to withhold the saccade. We recorded 290 units from two monkeys. From this group, 134 met two criteria, they did not show visual response in control trials and they had spike rates >2 Hz. These were analyzed further; 53% (71/134) showed modulation related to the target directed saccade, and 29% (39/134) showed saccadic modulation during spontaneous eye movements. These two groups were correlated only weakly. Of the units with significant saccadic modulation, 17% (12/71) showed significant directional selectivity, and 13% (9/71) showed significant position selectivity ( P < 0.01). At a lower criterion ( P < 0.05), almost one-half (33/71) showed one or the other spatial selectivity. Primates use saccades to acquire visual information. The appearance of strong saccadic modulation in brain structures previously characterized as mnemonic suggests the possibility that the mnemonic circuitry uses an extraretinal signal linked to saccades to control visual memory processes, e.g., synchronizing mnemonic processes to the pulsatile visual data inflow.
Response Properties of Saccade-Related Burst Neurons in the Central Mesencephalic Reticular Formation
Authors: Handel Ari , Glimcher Paul W.
Published: December 2017

Handel, Ari and Paul W. Glimcher. Response properties of saccade-related burst neurons in the central mesencephalic reticular formation. J. Neurophysiol. 78: 2164–2175, 1997. We studied the activity of saccade-related burst neurons in the central mesencephalic reticular formation (cMRF) in awake behaving monkeys. In experiment 1, we examined the activity of single neurons while monkeys performed an average of 225 delayed saccade trials that evoked gaze shifts having horizontal and vertical amplitudes between 2 and 20°. All neurons studied generated high-frequency bursts of activity during some of these saccades. For each neuron, the duration and frequency of these bursts of activity reached maximal values when the monkey made movements within a restricted range of horizontal and vertical amplitudes. The onset of the movement followed the onset of the burst by the longest intervals for movements within a restricted range of horizontal and vertical amplitudes. The range of movements for which this interval was longest varied from neuron to neuron. Across the population, these ranges included nearly all contraversive saccades with horizontal and vertical amplitudes between 2 and 20°. In experiment 2, we used the following task to examine the low-frequency prelude of activity that cMRF neurons generate before bursting: the monkey was required to fixate a light-emitting diode (LED) while two eccentric visual stimuli were presented. After a delay, the color of the fixation LED was changed, identifying one of the two eccentric stimuli as the saccadic target. After a final unpredictable delay, the fixation LED was extinguished and the monkey was reinforced for redirecting gaze to the identified saccadic target. Some cMRF neurons fired at a low frequency during the interval after the fixation LED changed color but before it was extinguished. For many neurons, the firing rate during this interval was related to the metrics of the movement the monkey made at the end of the trial and, to a lesser degree, to the location of the eccentric stimulus to which a movement was not directed.