bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells
Authors: Pitler T. A. , Alger B. E.
Published: December 2017

1. Whole cell voltage-clamp techniques were used in the CA1 region of rat hippocampal slices to study presynaptic and postsynaptic gamma-aminobutyric acid B (GABAB) response mechanisms. The effects of the protein kinase C activator phorbol 12,13-diacetate (PDA), barium (Ba2+), and pertussis toxin were compared on the presynaptic and postsynaptic GABAB actions of bath-applied baclofen and paired-pulse depression (PPD) of the monosynaptic GABAA inhibitory postsynaptic current (IPSC). The magnitude of PPD was dependent on the amplitude of the first response. PPD was predominantly a GABAB-mediated effect, as it was very much reduced by the GABAB antagonist CGP 35348. 2. PDA enhanced monosynaptic GABAA IPSCs through an apparently presynaptic mechanism. Iontophoretic GABAA responses were unaffected, and there was no change in EIPSC. PDA increased the frequency of spontaneous, tetrodotoxin-insensitive IPSCs without significantly affecting their amplitudes. The inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA application, stimulus intensity was adjusted to produce responses of comparable amplitude to control responses. PDA had a marked and reversible depressant effect on the postsynaptic GABAB response and caused a lesser, but still significant, reduction in the baclofen-induced reduction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramatically reduced postsynaptic GABAB responses; it had no effect on PPD. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs, although this was not statistically significant. 4. Pertussis toxin, injected 2–3 days earlier into the intact hippocampus, blocked all three GABAB responses equally (approximately 70% decrease). 5. We conclude that presynaptic and postsynaptic GABAB mechanisms are mediated by G proteins that couple to different mechanisms. Discrepancies with previous work are evidently due to the use of different tissue preparations and different target responses. Even though protein kinase C activation caused a partial reduction in the presynaptic effect of baclofen, its lack of effect on PPD makes a significant role for protein kinase C in modulation of PPD unlikely.
Age-related epileptogenic effects of corticotropin-releasing hormone in the isolated CA1 region of rat hippocampal slices
Authors: Smith B. N. , Dudek F. E.
Published: December 2017

1. The effects of corticotropin-releasing hormone (CRH) on synaptically evoked population and intracellular responses in the isolated rat CA1 region of hippocampal slices were studied to evaluate possible differences between adult and juvenile rats. 2. The amplitude of orthodromically evoked (stratum radiatum stimulation) population spikes was reversibly enhanced by 0.2–0.6 microM CRH to a greater extent in slices from juvenile rats than from adult rats. In no case, however, did CRH cause seizure-like activity to develop under normal recording conditions. 3. In the presence of 10–30 microM bicuculline, interictal-like bursts of population spikes and corresponding intracellularly recorded action potentials could be evoked starting at postnatal day 8. The number of spikes and the duration of the evoked bursts in the CA1 region were reversibly increased by CRH (0.2–0.6 microM) to a greater extent in slices from juvenile than from adult rats. 4. The amplitude of the afterhyperpolarization following intracellularly evoked bursts of action potentials in CA1 pyramidal cells was reduced by 0.2 microM CRH to a similar degree in both young and adult rats. No consistent changes in input resistance or membrane potential were observed. 5. No correlation was found between the magnitude of the CRH-induced increase in responsiveness and the initial excitability in controls, suggesting that the CRH-induced changes were independent of any age-dependent differences in general slice excitability. 6. Our results indicate that, in the CA1 region, CRH augments bicuculline-induced bursts to a greater extent in slices from young versus adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)
GABAB and adenosine receptors mediate enhancement of the K+ current, IAHP, by reducing adenylyl cyclase activity in rat CA3 hippocampal neurons
Authors: Gerber U. , Gahwiler B. H.
Published: December 2017

1. Gamma-aminobuturic acid-B (GABAB) and adenosine A1 receptors, which are expressed in hippocampal pyramidal cells, are linked to pertussis toxin-sensitive G-proteins known to be coupled negatively to the enzyme adenylyl cyclase. This study investigates the electrophysiological consequences of adenylyl cyclase inhibition in response to stimulation of these receptors. 2. Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal slice cultures in presence of tetrodotoxin. The calcium-dependent potassium current (IAHP), which is very sensitive to intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP), was used as an electrophysiological indicator of adenylyl cyclase activity. 3. Application of baclofen (10 microM), a selective agonist at GABAB receptors, or adenosine (50 microM) each resulted in a transient decrease followed by a significant enhancement in the amplitude of evoked IAHP. The initial reduction in amplitude of IAHP probably reflects inadequacies in voltage clamp of electronically distant dendritic sites, due to the shunting caused by concomitant activation of potassium conductance by baclofen/adenosine. Comparable increases in membrane conductance in response to the GABAA agonist, muscimol, caused a similar reduction in IAHP. The enhancement of IAHP is consistent with an inhibition of constitutively active adenylyl cyclase. 4. The receptor mediating the responses to adenosine was identified as belonging to the A1 subtype on the basis of its sensitivity to the selective antagonist 8-cyclopentyl-1,3-dipropylxanthine.(ABSTRACT TRUNCATED AT 250 WORDS)
Synaptic transmission between ventrolateral funiculus axons and lumbar motoneurons in the isolated spinal cord of the neonatal rat
Authors: Pinco M. , Lev-Tov A.
Published: December 2017

1. We studied the projections of ventrolateral funiculus (VLF) axons to lumbar motoneurons in the in vitro spinal cord preparation of 1- to 6-day-old rats using extracellular and sharp-electrode intracellular recordings. 2. Ipsilateral and contralateral VLF projections to lumbar motoneurons (L4-L5) could be activated in the neonatal rat by stimulation of the surgically peeled VLF at the rostral (L1-L2) and caudal lumbar (L6) cord. Motoneurons were activated ipsilaterally through short- and long-latency projections in all cases and contralaterally through long-latency projections in most cases. 3. Suppression of the excitatory components of VLF postsynaptic potentials (PSPs) by application of the specific antagonists of N-methyl D-aspartate (NMDA) and non-NMDA receptors, 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquin-oxaline-2,3-dione (CNQX), revealed depolarizing PSPs that could be reversed at -55 to -60 mV by injection of depolarizing current steps to the motoneurons. These depolarizing PSPs were blocked by addition of strychnine and bicuculline and are therefore suggested to be glycine and gamma-aminobutyric acid-A (GABAA) receptor-mediated inhibitory PSPs. The identity of a small (< or = 0.2 mV) residual depolarizing component that persisted in the presence of APV, CNQX, strychnine, and bicuculline remains to be determined. 4. Short-latency excitatory PSPs (EPSPs) could be resolved from the ipsilaterally elicited VLF PSPs after the reduction of the polysynaptic activity in the preparation by administration of mephenesin, which was followed by suppression of the glycine and GABAA receptor-mediated components of the PSPs by bath application of strychnine and bicuculline. The latencies of these EPSPs were similar to those of the monosynaptic dorsal root afferent EPSPs recorded from the same motoneurons. These short-latency VLF EPSPs were shortened by the NMDA antagonist APV and revealed an NMDA receptor-mediated component after administration of the non-NMDA receptor antagonist CNQX. Addition of the GABAB receptor agonist L-(-) baclofen or the glutamate analogue L-2-amino-4-phosphonobutyric acid (L-AP4) attenuated the pharmacologically resolved short-latency EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)
Development of thyrotropin-releasing hormone and norepinephrine potentiation of inspiratory-related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro
Authors: Funk G. D. , Smith J. C. , Feldman J. L.
Published: December 2017

1. The ontogeny of thyrotropin-releasing hormone (TRH) and norepinephrine (NE) potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0–3, P7, and P11-14 mice that retain functional networks for respiration. 2. TRH, applied locally to the XII motor nucleus, had no effect on XII inspiratory burst amplitude in slices from P0–3 mice. By P7 there was significant potentiation of burst amplitude that increased more than three-fold by P11–14. NE applied to the XII nucleus produced significant potentiation in all age groups. Potentiation increased developmentally with the largest increase occurring between P0–3 and P7. 3. Thus catecholamine and TRH modulation of inspiratory-related XII nerve activity increases during the first two weeks of life; the potentiating effects of NE appear prior to those of TRH. 4. With rhythmically active, transverse medullary slices from mice up to 2 wk of age, it is now possible to study the development of XII motoneuron modulation as it relates to respiratory control of the upper airway.
Modulation of anoxic injury in CNS white matter by adenosine and interaction between adenosine and GABA
Authors: Fern R. , Waxman S. G. , Ransom B. R.
Published: December 2017

1. We examined the role of adenosine in the development of anoxic injury in a CNS white matter tract, the rat optic nerve. Application of adenosine protected the rat optic nerve from anoxic injury; 2.5 microM adenosine increased compound action potential (CAP) recovery after a standard 60-min anoxic period from 28.6 +/- 2.5%, mean +/- SE, to 51.0 +/- 3.1% (P < 0001). The protective effect of adenosine was abolished by the adenosine receptor antagonist theophylline (100 microM). 2. The protective effect of adenosine evolved slowly after adenosine application; maximum protection required 60 min of adenosine exposure before the onset of anoxia. The concentration dependence of the protective effect was parabolic, with maximum protection at 2.5 microM. Neither high nor very low adenosine concentrations protected against anoxia. These characteristics are similar to those previously found for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the same preparation. 3. Inhibition of adenosine receptors (100 microM theophylline) reduced the level of recovery from that found under control conditions (24.3 +/- 4.8% compared with 36.2 +/- 2.5%, P < 0.05). The adenosine uptake inhibitor propentofylline, which potentiates release of endogenous adenosine during brain anoxia, significantly increased CAP recovery after anoxia. This effect was abolished by theophylline. It appeared therefore that release of endogenous adenosine limited injury in the optic nerve during anoxia. 4. The protective effect of adenosine was removed by pretreatment with the protein kinase C (PKC) inhibitor staurosporine (10 nM), indicating that activation of PKC was required for protection after exposure to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Purkinje cell complex spike activity during voluntary motor learning: relationship to kinematics
Authors: Ojakangas C. L. , Ebner T. J.
Published: December 2017

1. We examined the relationship of cerebellar Purkinje cell discharge to the scaling of kinematics during a voluntary motor learning paradigm. The study focused on whether the occurrence of complex spike (CS) discharge was associated with kinematic changes. Two primates (Macaca mulatta) were trained to move a cursor using a two-joint manipulandum over a horizontal video screen from a start target to one of four target boxes. The relationship between the cursor and the hand (gain) was changed, requiring scaling of movement distance to complete the task. As previously described, when the novel gain was presented over 100-200 movement trials the animals adapted their movements by using a strategy of scaling the amplitude and velocity of the first phase of the movement while keeping time to peak velocity constant. 2. The paradigm consisted of four different phases. A control phase at a gain of 1.0 was initially performed. The learning phase over the next 180-210 movements used one of four gains (0.6, 0.75, 1.5, or 2.0). Last, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials at the control gain of 1.0. The distance control phase consisted of using a gain of 1.0 but having the animal move to targets placed at the distance and direction the hand moved in the adapted state. 3. Simple spikes (SSs) and CSs of 141 Purkinje cells recorded primarily in the intermediate and lateral regions of zones V and VI in three cerebellar hemispheres from the two primates were recorded during the distance control, control, learning, and testing phases. Some cells were recorded in lobule VII and Crus I. CS activity increased during the learning phase, as documented previously. The increase in CS discharge occurred before or during the first 200-300 ms of the movement. This is the same time period in which the kinematic changes necessary for adaptation to the novel gain occur. Of 141 Purkinje cells recorded during the learning paradigm, 104 (74%) demonstrated significant increases in CS firing rate during the learning-testing phase. Of these 104 cells, 82 had statistically significant SS modulation. 4. Movement trials with CSs were separated from the trials without CSs. Aligning the kinematic and spike train data on movement onset, the average velocity profiles were subtracted from each other and a strict statistical criterion applied to test for the significance of any differences. Movement trials randomly sorted into two groups served as a control.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptic plasticity in the thalamo-cortical pathway as one of the neurobiological correlates of forelimb flexion conditioning: electrophysiological investigation in the cat
Authors: Meftah E. M. , Rispal-Padel L.
Published: December 2017

1. In a previous study, using a chronic cat preparation subjected to an associative conditioning procedure, we described the plasticity of the thalamo-cortical pathway by qualitatively and quantitatively analyzing the motor responses induced by stimulating each of the relays on the cerebello-thalamo-cortical pathway. In the present study, it was proposed to analyze the effects on the synapses located between thalamic endings and cortical neurones, using a twofold behavioral and electrophysiological approach, with a view to correlating the patterns of synaptic plasticity with the changes in the motor responses recorded. 2. For this purpose, a reduced, functionally organized sensorimotor circuit, which can be taken to be a neuronal analog of associative conditioning, was studied in an awake chronic animal preparation. This circuit was defined on the basis of the sites at which conditioned (CS) and unconditioned stimuli (UCS) were applied: the CS was applied at a site on the cerebellar interpositus nucleus which activated the forepaw musculature so as to induce flexion movements and the UCS was applied to the skin of the distal part of that paw so as to induce reflex flexion movements. By repetitively activating the central nervous pathways by the associated CS and UCS according to a predefined temporal pattern, the efficiency of the thalamo-cortical pathway's contribution to the movement production was enhanced, and its capacity to convey the cerebellar inputs to neurons in the motor cortex increased. 3. The associative nature of the conditioning was tested using previously established criteria. The setting up of motor and central changes in response to the repetitive presentation of paired CS and UCS, the fact that these changes were reversible because they could be abolished by applying extinction procedures, and the consistency of their occurrence whenever the CS was applied repeatedly alone for several days to naive animals, all showed that the stimuli of both kinds (CS and UCS) had to be applied together for the plasticity of the thalamo-cortical pathway to be expressed. 4. By determining whether the waves constituting the cerebello-cortical responses were excitatory or inhibitory, the nature of the changes in the transmission of the cerebellar impulses to neurons in the motor cortex was established.(ABSTRACT TRUNCATED AT 400 WORDS)
Hyperpolarization-activated Na(+)-K+ current (Ih) in neocortical neurons is blocked by external proteolysis and internal TEA
Authors: Budde T. , White J. A. , Kay A. R.
Published: December 2017

1. After 1 day in culture, neurons derived from the neonatal cerebral cortex of the rat exhibited a slowly activating current gated by hyperpolarizing voltage clamp pulses. The current was blocked by extracellular Cs+ and unaffected by extracellular Ba2+, and was permeable to both Na+ and K+ (PNa/PK = 0.29). Its form and pharmacology are consistent with a current termed Ih in other preparations. 2. Ih was absent from cells acutely dissociated from both the neonatal and mature cerebral cortex, despite the use of low enzyme concentrations. The sensitivity of Ih to extracellular proteolysis was demonstrated by superfusing the cells with trypsin (1 mg/ml) while monitoring the presence of Ih in the whole cell mode of recording. Ih was rapidly abolished (t1/2 approximately 5 min at 22 degrees C) by proteolysis and exhibited no shifts in its range of activation or changes in its activation kinetics during the course of the digestion. 3. Intracellular tetraethylammonium (TEA), at a concentration of < 15 mM was shown to block Ih completely, while extracellular TEA had no effect on the current. This suggests that the inner vestibule of Ih may be structurally related to that of potassium channels.
Use of interrupted saccade paradigm to study spatial and temporal dynamics of saccadic burst cells in superior colliculus in monkey
Authors: Keller E. L. , Edelman J. A.
Published: December 2017

1. We recorded the spatial and temporal dynamics of saccade-related burst neurons (SRBNs) found in the intermediate layers of the superior colliculus (SC) in the alert, behaving monkey. These burst cells are normally the first neurons recorded during radially directed microelectrode penetrations of the SC after the electrode has left the more dorsally situated visual layers. They have spatially delimited movement fields whose centers describe the well-studied motor map of the SC. They have a rather sharp, saccade-locked burst of activity that peaks just before saccade onset and then declines steeply during the saccade. Many of these cells, when recorded during saccade trials, also have an early, transient visual response and an irregular prelude of presaccadic activity. 2. Because saccadic eye movements normally have very stereotyped durations and velocity trajectories that vary systematically with saccade size, it has been difficult in the past to establish quantitatively whether the activity of SRBNs temporally codes dynamic saccadic control signals, e.g., dynamic motor error or eye velocity, where dynamic motor error is defined as a signal proportional to the instantaneous difference between desired final eye position and the actual eye position during a saccade. It has also not been unequivocally established whether SRBNs participate in an organized spatial shift of ensemble activity in the intermediate layers of the SC during saccadic eye movements. 3. To address these issues, we studied the activity of SRBNs using an interrupted saccade paradigm. Saccades were interrupted with pulsatile electrical stimulation through a microelectrode implanted in the omnipauser region of the brain stem while recordings were made simultaneously from single SRBNs in the SC. 4. Shortly after the beginning of the stimulation (which was electronically triggered at saccade onset), the eyes decelerated rapidly and stopped completely. When the high-frequency (typically 300-400 pulses per second) stimulation was terminated (average duration 12 ms), the eye movement was reinitiated and a resumed saccade was made accurately to the location of the target. 5. When we recorded from SRBNs in the more caudal colliculus, which were active for large saccades, cell discharge was powerfully and rapidly suppressed by the stimulation (average latency = 3.8 ms). Activity in the same cells started again just before the onset of the resumed saccade and continued during this saccade even though it has a much smaller amplitude than would normally be associated with significant discharge for caudal SC cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Receptive-field size of L1 horizontal cells in the turtle retina: effects of dopamine and background light
Authors: Perlman I. , Ammermuller J.
Published: December 2017

1. The receptive-field size of turtle L1 horizontal cells was assessed qualitatively from the small-spot/full-field-response amplitude ratio. For quantitative evaluation, the length constant was derived from the response amplitude-spot radius relationship. 2. In each horizontal cell, the length constants were calculated for different intensities of the test light stimuli. The effects of dopamine and/or background light on the small-spot/full-field amplitude ratio and on the length constants were studied. 3. The receptive field of an L1 horizontal cell could not be defined by a single length constant of fixed value. Rather, the length constant changed with the experimental conditions. Two types of changes were noted. An instantaneous one, which was expressed in an increase in the length constant when the test flash was made brighter, and a slow one that occurred when the eyecup was exposed to dopamine. 4. Dopamine increased the small-spot/full-field amplitude ratio and reduced the length constant for a given full-field-response amplitude. It did not alter the responsiveness to light of the horizontal cells. These effects of dopamine were consistent with its action on the coupling resistance between adjacent horizontal cells. 5. Continuous background illumination increased the small-spot/full-field-response amplitude ratio whether studied in normal Ringer or during superfusion with dopamine solution. 6. The relationship between the length constants and the relative amplitude of the full-field responses did not change when the level of ambient illumination was raised either during superfusion with normal Ringer solution or during superfusion with dopamine solution. 7. These data indicate that background lights do not alter the receptive field size of turtle L1 horizontal cells.
On temporal codes and the spatiotemporal response of neurons in the lateral geniculate nucleus
Authors: Golomb D. , Kleinfeld D. , Reid R. C. , Shapley R. M. , Shraiman B. I.
Published: December 2017

1. The present work relates recent experimental studies of the temporal coding of visual stimuli (McClurkin, Optican, Richmond, and Gawne, Science 253: 675, 1991) to the measurements of the spatiotemporal receptive fields of neurons within the lateral geniculate of primate. 2. We analyze both new and previously described magnocellular and parvocellular single units. The spatiotemporal impulse response function of the unit, defined as the time-resolved average firing rate in response to a weak stimulus flashed at a given location and time, is characterized by the singular value decomposition. This analysis allows one to represent the impulse response by a small number, two to three, of spatial and temporal modes. Both magnocellular and parvocellular units are weakly nonseparable, with major and minor modes that account, respectively, for approximately 78 and 22% of the response. The major temporal mode for both types is essentially identical for the first 100 ms. At later times the response of magnocellular units changes sign and decays slowly, whereas the response of parvocellular units decays relatively rapidly. 3. The spatiotemporal impulse response function completely determines the response of a unit to an arbitrary stimulus when linear response theory is valid. Using the measured impulse response, combined with a rectifying neuronal input-output relation, we calculate the responses to a complete set of spatial luminance patterns constructed of "Walsh" functions. Our predicted temporal responses are in qualitative agreement with those reported for parvocellular units (McClurkin, Optican, Richmond, and Gawne, J. Neurophysiol. 66: 794, 1991). Under the additional assumptions of Poisson statistics for the probability of spiking and a plausible background firing rate, we predict the performance of a unit in the Walsh pattern discrimination task as quantified by mutual information. Our prediction is again consistent with the reported results. 4. Last, we consider the issue of temporal coding within linear response. For stimuli presented for fixed time intervals, the singular value decomposition provides a natural relation between the temporal modes of the neuronal response and the spatial pattern of the stimulus. Although it is tempting to interpret each temporal mode as an independent channel that encodes orthogonal features of the stimulus, successively higher order modes are increasingly unreliable and do not significantly increase the discrimination capabilities of the unit.
Urge to scratch represented in the human cerebral cortex during itch
Authors: Hsieh J. C. , Hagermark O. , Stahle-Backdahl M. , Ericson K. , Eriksson L. , Stone-Elander S. , Ingvar M.
Published: December 2017

1. We used functional positron emission tomography (PET), measuring regional cerebral blood flow (rCBF) as an index of neuronal activity, to investigate the central processing of itch in 10 healthy volunteers subjected to intracutaneous injections of histamine. 2. The study has unraveled a central representation that depicts a motor intention of the urge to scratch contingent on the perception of unpleasant itch. The coactivation of the anterior cingulate cortex (ACC), supplementary motor area (SMA), premotor area (PM), and inferior parietal lobule (IPL) substantiates that the posterior sector of the ACC (Brodmann 24) is related to the sensorial/affectional aspect of the event. The premotor cortical areas (SMA, PM) and the IPL may participate in the preparation of an intended action.
Postnatal development of pre- and postsynaptic GABAB-mediated inhibitions in the CA3 hippocampal region of the rat
Authors: Gaiarsa J. L. , Tseeb V. , Ben-Ari Y.
Published: December 2017

1. Intracellular recordings were made from adult and neonatal rat hippocampal slices to study the postnatal development of GABAB-mediated inhibition in CA3 pyramidal neurons. 2. In the presence of glutamatergic receptor antagonists, direct electrical stimulation of the interneurons induced a biphasic GABAA- and GABAB-mediated inhibitory postsynaptic potential in adult [postnatal day (P) 30-P40] and young (P6-P8) CA3 pyramidal neurons. In contrast, in pups (P0-P3), electrical stimulation only induced a bicuculline-sensitive depolarizing GABAA synaptic potential. 3. The outward postsynaptic currents generated by bath-applications of baclofen (30 microM, 30 s) at P3 (78 +/- 60 pA, mean +/- SE) were 4 to 5 times smaller than those evoked between P6 (329 +/- 32 pA) and P30 (412 +/- 44 pA). At P0, baclofen failed to induce a postsynaptic current. 4. The outward currents generated by serotonin (50 microM, 30 s) and the A1 receptor agonist N-cyclopentyladenosine (40 microM, 30 s) ranged between 0 and 50 pA at P3 and between 200 and 400 pA at P6 and P30 (holding potential = -60 +/- 2 mV). 5. In the presence of potassium channel blockers, the amplitude of calcium current elicited by a depolarizing voltage step command (1 s) from a holding potential of -60 mV to a test potential of 0 mV was 2 +/- 0.15 nA at P6 (n = 9) and 0.73 +/- 0.14 nA at P3 (n = 8). Baclofen reversibly reduced the amplitude of calcium currents in young rats but not in pups. 6. Baclofen reversibly reduced the amplitude of the evoked GABAA-mediated and glutamatergic synaptic events at all developmental stages. These effects were dose dependent and antagonized by P-alpha 3-aminopropyl-P-diethoxymethyl-phosphinic acid (CGP) 35348 (500 microM). 7. We conclude that postsynaptic GABAB-mediated inhibition is absent or minimal during the first postnatal days in the CA3 region. In contrast, presynaptic GABAB inhibition is present at birth. We discuss the mechanisms and physiological consequences of these observations.
Properties of ATP-gated channels recorded from rat sympathetic neurons: voltage dependence and regulation by Zn2+ ions
Authors: Cloues R.
Published: December 2017

1. I recorded ATP-gated channels from excised outside-out patches from rat sympathetic neurons. The channels had a unitary conductance of approximately 12 pS at -80 mV, were activated only when ATP was present in the bath, and could be blocked by the P2-purinoceptor antagonist suramin. 2. The open probability of the channels showed a strong voltage dependence, increasing significantly with hyperpolarization. This suggests that whole cell rectification of currents evoked by P2X receptor activation is a result of channel voltage dependence and not of properties of ion permeation. 3. Low concentrations of extracellular Zn2+, which has previously been shown to potentiate whole cell ATP-evoked currents, increased the open probability of ATP-gated channels without altering the unitary conductance. 4. Zn2+ increased both the opening frequency and the burst duration of ATP-gated channels. The results are consistent with Zn2+ acting as an allosteric modulator of the P2X receptor in sympathetic neurons.
Impairments of reaching movements in patients without proprioception. II. Effects of visual information on accuracy
Authors: Ghez C. , Gordon J. , Ghilardi M. F.
Published: December 2017

1. The aim of this study was to determine how vision of a cursor indicating hand position on a computer screen or vision of the limb itself improves the accuracy of reaching movements in patients deprived of limb proprioception due to large-fiber sensory neuropathy. In particular, we wished to ascertain the contribution of such information to improved planning rather than to feedback corrections. We analyzed spatial errors and hand trajectories of reaching movements made by subjects moving a hand-held cursor on a digitizing tablet while viewing targets displayed on a computer screen. The errors made when movements were performed without vision of their arm or of a screen cursor were compared with errors made when this information was available concurrently or prior to movement. 2. Both monitoring the screen cursor and seeing their limb in peripheral vision during movement improved the accuracy of the patients' movements. Improvements produced by seeing the cursor during movement are attributable simply to feedback corrections. However, because the target was not present in the actual workspace, improvements associated with vision of the limb must involve more complex corrective mechanisms. 3. Significant improvements in performance also occurred in trials without vision that were performed after viewing the limb at rest or during movements. In particular, prior vision of the limb in motion improved the ability of patients to vary the duration of movements in different directions so as to compensate for the inertial anisotropy of the limb. In addition, there were significant reductions in directional errors, path curvature, and late secondary movements. Comparable improvements in extent, direction, and curvature were produced when subjects could see the screen cursor during alternate movements to targets in different directions. 4. The effects of viewing the limb were transient and decayed during a period of minutes once vision of the limb was no longer available. 5. It is proposed that the improvements in performance produced after vision of the limb were mediated by the visual updating of internal models of the limb. Vision of the limb at rest may provide configuration information while vision of the limb in motion provides additional dynamic information. Vision of the cursor and the resulting ability to correct ongoing movements, however, is considered primarily to provide information about the dynamic properties of the limb and its response to neural commands.
Functional anatomy of the mental representation of upper extremity movements in healthy subjects
Authors: Stephan K. M. , Fink G. R. , Passingham R. E. , Silbersweig D. , Ceballos-Baumann A. O. , Frith C. D. , Frackowiak R. S.
Published: December 2017

1. Differences in the distribution of relative regional cerebral blood flow during motor imagery and execution of a joy-stick movement were investigated in six healthy volunteers with the use of positron emission tomography (PET). Both tasks were compared with a common baseline condition, motor preparation, and with each other. Data were analyzed for individual subjects and for the group, and areas of significant flow differences were related to anatomy by magnetic resonance imaging (MRI). 2. Imagining movements activated a number of frontal and parietal regions: medial and lateral premotor areas, anterior cingulate areas, ventral opercular premotor areas, and parts of superior and inferior parietal areas were all activated bilaterally when compared with preparation to move. 3. Execution of movements compared with imagining movements led to additional activations of the left primary sensorimotor cortex and adjacent areas: dorsal parts of the medial and lateral premotor cortex; adjacent cingulate areas; and rostral parts of the left superior parietal cortex. 4. Functionally distinct rostral and caudal parts of the posterior supplementary motor area (operationally defined as the SMA behind the coronal plane at the level of the anterior commissure) were identified. In the group, the rostral part of posterior SMA was activated by imagining movements, and a more caudoventral part was additionally activated during their execution. A similar dissociation was observed in the cingulate areas. Individual subjects showed that the precise site of these activations varied with the individual anatomy; however, a constant pattern of preferential activation within separate but adjacent gyri of the left hemisphere was preserved. 5. Functionally distinct regions were also observed in the parietal lobe: the caudal part of the superior parietal cortex [medial Brodmann area (BA) 7] was activated by imagining movements compared with preparing to execute them, whereas the more rostral parts of the superior parietal lobe (BA 5), mainly on the left, were additionally activated by execution of the movements. 6. Within the operculum, three functionally distinct areas were observed: rostrally, prefrontal areas (BA 44 and 45) were more active during imagined than executed movements; a ventral premotor area (BA 6) was activated during both imagined and executed movements; and more caudally in the parietal lobe, an area was found that was mainly activated by execution presumably SII. 7. These data suggest that imagined movements can be viewed as a special form of "motor behavior' that, when compared with preparing to move, activate areas associated heretofore with selection of actions and multisensory integration.(ABSTRACT TRUNCATED AT 400 WORDS)
Hippocampal inhibitory neuron activity in the elevated potassium model of epilepsy
Authors: McBain C. J.
Published: December 2017

1. Whole cell patch-clamp recordings were made from CA1 stratum oriens inhibitory neurons of rat hippocampal slices in vitro to determine their contribution to the epileptiform activity elicited by elevating the extracellular potassium ion concentration ([K+]o) from 3.5 to 8.5 mM. 2. Under current-clamp conditions, spontaneous action potential activity in inhibitory neurons normally occurs in a sustained repetitive firing mode paced by nonsynaptic, intrinsic mechanisms. On elevation of [K+]o to 8.5 mM the pattern of activity is altered such that clusters of action potentials occur interrupted by periods of silence without an appreciable after hyperpolarization (AHP). In addition, elevation of [K+]o caused a large reduction in the action potential AHP amplitude and duration concomitant with a 20-mV shift in the reversal potential of the AHP. 3. In voltage clamp a small persistent inward current was observed after the introduction of elevated potassium concomitant with an increase in the frequency of spontaneous excitatory post-synaptic currents (EPSCs) in all interneurons studied. After a short period of time (approximately 1 min) temporal summation of synchronously occurring EPSCs contributed a periodic inward current (PIC; 10-40 pA, 0.8 Hz) that persisted for the duration of the [K+]o elevation. Analysis of the charge transfer associated with the PIC suggests that they comprise the temporal summation of approximately 35 EPSCs. This PIC was synchronous with the extracellular field potential recorded from the CA1 pyramidal neuron layer. 4. The PIC was responsible for the clustering of action potential activity because blockade of EPSC activity by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) abolished PICs and reverted action potential activity to single sustained firing, despite the continued application of 8.5 mM [K+]o. Antagonists of N-methyl-D-aspartate receptors were without effect on either the PICs or the action potential activity. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonist (+)-2-methyl-4-carboxyphenylglycine (MCPG) reversibly abolished the PIC without affecting the increase in EPSC frequency. 6. Recordings from CA3 pyramidal neurons in 8.5 mM [K+]o demonstrated that interictal activity occurred at a frequency identical to the PICs observed in interneurons. Interictal activity in CA3 pyramidal neurons was attenuated but never abolished by MCPG, suggesting a role for mGluR receptors in the maintenance of interictal activity in area CA3.(ABSTRACT TRUNCATED AT 400 WORDS)
Spontaneous and sound-evoked discharge characteristics of complex-spiking neurons in the dorsal cochlear nucleus of the unanesthetized decerebrate cat
Authors: Parham K. , Kim D. O.
Published: December 2017

1. We examined the spontaneous and sound-evoked discharge characteristics of 20 complex-spiking units recorded in the dorsal cochlear nucleus (DCN) of 15 unanesthetized, decerebrate cats. 2. The extracellularly recorded complex spikes consisted of bursts of two to five action potentials whose size gradually decreased during the burst. Complex spikes were observed both in the spontaneous and sound-evoked activity of the units in our sample. 3. The spontaneous rates (SRs) of DCN complex-spiking units ranged from 0 to 30 spikes/s. Spontaneous activity consisted of complex and simple (i.e., the common single neuronal action potential) spikes. Comparison of the SR distributions of the DCN complex-spiking units with that of a total sample of 194 DCN units (from 9 cats) suggests that the complex-spiking units tended to be in the lower half of the DCN SR distribution. 4. Sound-evoked discharges could consist of both complex and simple spikes. On the basis of their sound-driven responses, we divided the DCN complex-spiking units into two groups. The majority (15 of 20, 75%) were weakly driven by pure tones and inhibited by broadband noise. They tended to have broad response areas. Their response latencies to pure tone and noise stimuli were relatively long (10-20 ms). The recording depths of these units tended to be superficial (i.e., 10 of 15 units were located within 400 microns of the dorsal surface of the DCN). A minority (5 of 20, 25%) of the complex-spiking units were strongly driven by pure tone and broadband noise stimuli. These units had more clearly defined excitatory regions of response areas than the weakly driven units. Their response latencies to pure tone and noise stimuli were short (< 10 ms). The recording depths of these units tended to be deeper (i.e., 4 of 5 units were located at 400-700 microns) than those of the weakly driven units. 5. Intracellular recording and labeling studies of in vitro DCN slice preparations have correlated complex spikes with the superficially located cartwheel cells. Given the complex spikes of the units, many of which were located superficially, we suggest that our sample, particularly the weakly driven group of neurons, corresponds to the cartwheel cells. 6. Cartwheel cells are putative inhibitory interneurons whose axons primarily contact on the main projection neurons of DCN, the fusiform cells. The present finding of sound-evoked discharges by the superficially located complex-spiking units suggests that cartwheel cells should play a role in modifying the sound-evoked responses of the fusiform cells.
Rescue of motoneuron and muscle afferent function in cats by regeneration into skin. I. Properties of afferents
Authors: Johnson R. D. , Taylor J. S. , Mendell L. M. , Munson J. B.
Published: December 2017

1. In this study we investigate the peripheral receptive field properties and spinal cord connections of low-threshold muscle afferent fibers cross-regenerated into the skin to determine whether a cutaneous target can rescue physiological functions lost after chronic axotomy. 2. In adult cats the medial gastrocnemius (MG) muscle nerve was coated with the distal cut end of either the caudal or lateral cutaneous sural nerves and allowed to regenerate into the hairy skin (postoperative period 6-30 mo). During terminal acute experiments we made recordings of single MG afferent fibers in dorsal root filaments and peripheral nerve. Conduction velocity and receptive field characteristics were determined for each fiber. In addition, the MG nerve was stimulated to elicit cord dorsum potentials and monosynaptic excitatory postsynaptic potentials (EPSPs) in heteronymous motoneurons. As controls, studies were carried out after MG nerve axotomy (postoperative period 2.5-12 mo). 3. After innervation of the skin, MG muscle afferent fibers exhibited firing characteristics and proximal segment conduction velocities like those of normal MG afferents. Responses to skin and hair stimulation consisted primarily of slowly adapting, stretch-sensitive, and steady discharge patterns, all common in normal muscle afferents but not in cutaneous afferents. These properties were observed despite the innervation of touch domes and single hairs, suggesting that the peripheral physiology of muscle afferents is a function of the axonal membrane and is not respecified by a cutaneous target and/or receptors. 4. Cord dorsum potentials were characteristic of those elicited by intact muscle afferents rather than skin afferents and showed recovery of configurations lost after chronic axotomy. 5. The monosynaptic EPSPs elicited in lateral gastrocnemius-soleus motoneurons also recovered from the reduction in amplitude observed after chronic axotomy. The configurations of these EPSPs were characteristic of muscle afferents rather than skin afferents. 6. These experiments demonstrate that the peripheral and central physiological properties of muscle afferents are rescued from the axotomy state if the afferents are allowed to reinnervate skin. We found no evidence that respecification had occurred to bring the function of muscle afferents into accord with the new cutaneous target.
Rescue of motoneuron and muscle afferent function in cats by regeneration into skin. II. Ia-motoneuron synapse
Authors: Mendell L. M. , Taylor J. S. , Johnson R. D. , Munson J. B.
Published: December 2017

1. In this study we describe application of high-frequency stimulation to the group Ia afferent-to-motoneuron synapse of cats to determine the extent to which regeneration of axotomized muscle afferents and motoneurons into skin or into muscle rescues their ability to generate excitatory postsynaptic potentials (EPSPs). 2. The medial gastrocnemius (MG) muscle nerve was transected and 1) left chronically axotomized, 2) cross-united to the caudal cutaneous sural (CCS) nerve, or 3) self-united. The ability of the operated MG muscle afferents to generate EPSPs in normal lateral gastrocnemius-soleus (LGS) motoneurons and of normal LGS muscle afferents to generate EPSPs in the operated MG motoneurons was tested 5 wk-30 mo later. 3. EPSPs were generated by bursts of 32 shocks at 167 Hz and averaged in register. In normal cats, EPSP amplitude decreased (negative modulation) during these bursts in type S motoneurons and could increase or decrease in type F motoneurons (positive or negative modulation). 4. After axotomy, EPSPs generated both in axotomized motoneurons and by axotomized afferents showed only negative modulation during the burst, and the negative modulation was much greater than in normal animals. Regeneration of the muscle nerve into skin significantly decreased the negative modulation relative to axotomy. Regeneration of the muscle nerve into muscle restored the EPSP modulation behaviors even more, to essentially normal values. 5. We conclude that the ability of muscle afferents to generate EPSPs in motoneurons in response to high-frequency stimulation, and the ability of motoneurons to express those EPSPs, are both influenced by the target innervated by those neurons. Synaptic efficacy is severely reduced by target deprivation (axotomy), partially rescued by cross-regeneration into skin, and rescued virtually completely by regeneration into the native muscle. We speculate on the role of target-derived neurotrophins in these effects.
Effect of ON pathway blockade on directional selectivity in the rabbit retina
Authors: Kittila C. A. , Massey S. C.
Published: December 2017

1. In this report we describe extracellular recordings made from directionally selective (DS) ganglion cells in the rabbit retina during perfusion with 2-amino-4-phosphonobutyric acid (APB) to block ON channels through the retina. 2. Application of 100 microM APB selectively and reversibly abolished the responses of ON ganglion cells in the rabbit retina. In addition, 100 microM APB completely and reversibly blocked ON component responses of ON-OFF DS ganglion cells to both stationary and moving stimuli. These results are consistent with the idea that APB blocks ON pathways through the retina. 3. Under ON pathway blockade with APB, OFF component responses of ON-OFF DS ganglion cells remained DS. DS OFF responses retained the same preferred direction as the pre-APB ON-OFF responses and could be driven using either normal or reversed contrast stimuli. 4. Extracellular responses of ON DS ganglion cells were completely blocked by APB. Under APB, these cells showed no response to stationary or moving stimuli. 5. Application of the gamma-aminobutyric acid-A (GABAA) antagonist 2-(3-Carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide (SR95531) reversibly abolished directional selectivity of ON DS and ON-OFF DS ganglion cells in the rabbit retina. This finding is consistent with previous data for picrotoxin. 6. Application of SR95531 during ON channel blockade by APB caused OFF component responses of ON-OFF DS ganglion cells to lose their directional selectivity. Under these conditions, OFF responses to movement in the preferred and null directions became virtually identical. 7. These results indicate that simultaneous ON and OFF layer input is not required to generate directional responses in ON-OFF DS ganglion cells. In addition, it appears that a GABAA-dependent mechanism for directional selectivity may operate independently in the two separate dendritic layers of the ON-OFF DS ganglion cell.