bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Intracellular Dialysis of ATP on the Hyperpolarization-Activated Cation Current in Rat Dorsal Root Ganglion Neurons
Authors: Komagiri You , Kitamura Naoki
Published: May 2006

The mechanism of the effect of intracellular ATP on the hyperpolarization-activated non-selective cation current ( Ih) in rat dorsal root ganglion neurons was investigated using a whole cell voltage-clamp technique. Under voltage-clamp conditions, Ihwas activated by hyperpolarizing pulses raised to a voltage of between –70 and –130 mV. The activation curve of Ihin rat dorsal root ganglion (DRG) neurons shifted by about 15 mV in the positive direction with an intracellular solution containing 1 mM cAMP. When ATP (2 mM) was applied intracellularly, the half-maximal activation voltage ( Vhalf) of Ihshifted from –97.4 ± 1.9 to –86.8 ± 1.6 mV, resulting in an increase in the current amplitude of Ihby the pulse to between –80 and –90 mV. In the presence of an adenylate cyclase inhibitor, SQ-22536 (100 μM), the intracellular dialysis of ATP also produced a shift in the voltage-dependence of Ihin rat DRG neurons, indicating that the effect of ATP was not caused by cAMP converted by adenylate cyclase. Intracellular dialysis of a nonhydrolysable ATP analog, AMP-PNP or ATP-γ-S, also produced a positive shift in the voltage-dependence of Ihactivation, suggesting that the effect of ATP results from its direct action on the channel protein. These results indicate that cytosolic ATP directly regulates the voltage dependence of Ihactivation as an intracellular modulating factor.
Receptive Field Properties and Laminar Organization of Lateral Geniculate Nucleus in the Gray Squirrel (Sciurus carolinensis)
Authors: Van Hooser Stephen D. , Heimel J. Alexander F. , Nelson Sacha B.
Published: May 2006

Physiological studies of the lateral geniculate nucleus (LGN) have revealed three classes of relay neurons, called X, Y, and W cells in carnivores and parvocellular (P), magnocellular (M), and koniocellular (K) in primates. The homological relationships among these cell classes and how receptive field (RF) properties of these cells compare with LGN cells in other mammals are poorly understood. To address these questions, we have characterized RF properties and laminar organization in LGN of a highly visual diurnal rodent, the gray squirrel, under isoflurane anesthesia. We identified three classes of LGN cells. One class found in layers 1 and 2 showed sustained, reliable firing, center-surround organization, and was almost exclusively linear in spatial summation. Another class, found in layer 3, showed short response latencies, transient and reliable firing, center-surround organization, and could show either linear (76%) or nonlinear (24%) spatial summation. A third, heterogeneous class found throughout the LGN but primarily in layer 3 showed highly variable responses, a variety of response latencies and could show either center-surround or noncenter-surround receptive field organization and either linear (77%) or nonlinear (23%) spatial summation. RF sizes of all cell classes showed little dependency on eccentricity, and all of these classes showed low contrast gains. When compared with LGN cells in other mammals, our data are consistent with the idea that all mammals contain three basic classes of LGN neurons, one showing reliable, sustained responses, and center-surround organization (X or P); another showing transient but reliable responses, short latencies, and center-surround organization (Y or M); and a third, highly variable and heterogeneous class of cells (W or K). Other properties such as dependency of receptive field size on eccentricity, linearity of spatial summation, and contrast gain appear to vary from species to species.
Na+Channel Expression and Neuronal Function in the Na+/H+Exchanger 1 Null Mutant Mouse
Authors: Xia Ying , Zhao Peng , Xue Jin , Gu Xiang Q. , Sun Xiaolu , Yao Hang , Haddad Gabriel G.
Published: May 2006

Mice lacking Na+/H+exchanger 1 (NHE1) suffer from recurrent seizures and die early postnatally. Although the mechanisms for seizures are not well established, our previous electrophysiological work has shown that neuronal excitability and Na+current density are increased in hippocampal CA1 neurons of these mutant mice. However, it is unknown whether this increased density is related to altered expression or functional regulation of Na+channels. In this work, we asked three questions: is the increased excitability limited to CA1 neurons, is the increased Na+current density related to an increased Na+channel expression, and, if so, which Na+channel subtype(s) is upregulated? Using neurophysiological, autoradiographic, and immunoblotting techniques, we showed that both CA1 and cortical neurons have an increase in membrane excitability and Na+current density; Na+channel density is selectively upregulated in the hippocampus and cortex ( P < 0.05); and Na+channel subtype I is significantly increased in the hippocampus and Na+channel subtype II is increased in the cortex. Our results demonstrate that mice lacking NHE1 upregulate their Na+channel expression in the hippocampal and cortical regions selectively; this leads to an increase in Na+current density and membrane excitability. We speculate that neuronal overexcitability due to Na+channel upregulation in the hippocampus and cortex forms the basis of epileptic seizures in NHE1 mutant mice.
Increased Electrotonic Coupling in Spinal Motoneurons After Transient Botulinum Neurotoxin Paralysis in the Neonatal Rat
Authors: Pastor Angel M. , Mentis George Z. , De la Cruz Rosa R. , Díaz Eugenia , Navarrete Roberto
Published: May 2006

The effect of early postnatal blockade of neuromuscular transmission using botulinum neurotoxin (BoNT) type A on motoneuron gap junctional coupling was studied by means of intracellular recordings and biocytin labeling using the in vitro hemisected spinal cord preparation of neonatal rats. The somata of tibialis anterior (TA) motoneurons were retrogradely labeled at birth (P0) by intramuscular injection of fluorescent tracers. Two days later, BoNT was injected unilaterally into the TA muscle. The toxin blocked neuromuscular transmission for the period studied (P4–P7) as shown by tension recordings of the TA muscle. Retrograde horseradish peroxidase tracing in animals reared to adulthood demonstrated no significant cell death or changes in the soma size of BoNT-treated TA motoneurons. Intracellular recordings were carried out in prelabeled control and BoNT-treated TA motoneurons from P4 to P7. Graded stimulation of the ventral root at subthreshold intensities elicited short-latency depolarizing (SLD) potentials that consisted of several discrete components reflecting electrotonic coupling between two or more motoneurons. BoNT treatment produced a significant increase (67%) in the maximum amplitude of the SLD and in the number of SLD components as compared with control (3.1 ± 1.7 vs. 1.4 ± 0.7; means ± SD). The morphological correlates of electrotonic coupling were investigated at the light microscope level by studying the transfer of biocytin to other motoneurons and the putative sites of gap junctional interaction. The dye-coupled neurons clustered around the injected cell with close somato-somatic, dendro-somatic and -dendritic appositions that might represent the sites of electrotonic coupling. The size of the motoneuron cluster was, on average, 2.2 times larger after BoNT treatment. Our findings demonstrate that a short-lasting functional disconnection of motoneurons from their target muscle delays motoneuron maturation by halting the elimination of gap junctional coupling that normally occurs during early postnatal development.
Vibrissa Movement Elicited by Rhythmic Electrical Microstimulation to Motor Cortex in the Aroused Rat Mimics Exploratory Whisking
Authors: Berg Rune W. , Kleinfeld David
Published: May 2006

The rhythmic motor activity of the vibrissae that rodents use for the tactile localization of objects provides a model system for understanding patterned motor activity in mammals. Evidence suggests that neural circuitry in the brain stem provides rhythmic drive to the vibrissae. Yet multiple brain structures at higher levels of organization, including vibrissa primary motor cortex (M1), have direct projections to brain stem nuclei that are implicated in whisking. We thus asked whether output from M1 can control vibrissa movement on the approximately 10-Hz scale of the natural rhythmic movement of the vibrissae. Our assay of cortical control made use of periodic intracortical microstimulation (ICMS) to excite a region of vibrissa M1 cortex in awake, behaving animals and measurements of the stimulus-locked electromyogram (EMG) in both the intrinsic and extrinsic muscles that drive the vibrissae. We observed that ICMS evoked a prompt activation of the extrinsic muscles and a delayed and prolonged response in the intrinsic muscles. The relative timing and shape of these waveforms approximates the EMG waveforms seen during natural exploratory whisking. We further observed prompt activation of the intrinsic muscles, an occurrence not seen during exploratory whisking. Despite the latter difference in muscular activation, the motion of the vibrissae evoked by periodic ICMS strongly resembled the motion during natural, exploratory whisking. Interestingly, the extent of the movement was proportional to the level of arousal, as quantified by the amplitude of hippocampal activity in the theta frequency band. We interpret these data as demonstrating that M1 cortex can, in principle, initiate the full pattern of whisking on a cycle-by-cycle basis in aroused animals. Beyond issues of natural motor control, our result may bear on the design of algorithms for neuroprosthetic control of motor output.
Nitric Oxide Inhibits Spinally Projecting Paraventricular Neurons Through Potentiation of Presynaptic GABA Release
Authors: Li De-Pei , Chen Shao-Rui , Pan Hui-Lin
Published: May 2006

Nitric oxide (NO) in the paraventricular nucleus (PVN) is involved in the regulation of the excitability of PVN neurons. However, the effect of NO on the inhibitory GABAergic and excitatory glutamatergic inputs to spinally projecting PVN neurons has not been studied specifically. In the present study, we determined the role of the inhibitory GABAergic and excitatory glutamatergic inputs in the inhibitory action of NO on spinally projecting PVN neurons. Spinally projecting PVN neurons were retrogradely labeled by a fluorescent dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocasbocyane (DiI), injected into the spinal cord of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled PVN neurons in the hypothalamic slice. The spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in DiI-labeled neurons were abolished by 20 μM bicuculline, whereas the miniature excitatory postsynaptic currents (mEPSCs) were eliminated by 20 μM 6-cyano-7-nitroquinoxaline-2,3-dione. Bath application of an NO donor, 100 μM S-nitroso- N-acetyl-penicillamine (SNAP), or the NO precursor, 100 μM l-arginine, both significantly increased the frequency of mIPSCs of DiI-labeled PVN neurons, without altering the amplitude and the decay time constant of mIPSCs. The effect of SNAP and l-arginine on the frequency of mIPSCs was eliminated by an NO scavenger, 2-(4-carboxypheny)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, and an NO synthase inhibitor, 1-(2-trifluoromethylphenyl) imidazole, respectively. Neither SNAP nor l-arginine significantly altered the frequency and the amplitude of mEPSCs. Under current-clamp conditions, 100 μM SNAP or 100 μM l-arginine significantly decreased the discharge rate of the DiI-labeled PVN neurons, without significantly affecting the resting membrane potential. On the other hand, 20 μM bicuculline significantly increased the impulse activity of PVN neurons. In the presence of bicuculline, SNAP or l-arginine both failed to inhibit the firing activity of PVN neurons. This electrophysiological study provides substantial new evidence that NO suppresses the activity of spinally projecting PVN neurons through potentiation of the GABAergic synaptic input.
Stereotypical Fingertip Trajectories During Grasp
Authors: Kamper D. G. , Cruz E. G. , Siegel M. P.
Published: May 2006

The kinematics of movement of all five digits was analyzed during reach-and-grasp tasks for a variety of objects. Ten healthy subjects performed 20 trials involving the grasp of five objects of distinct size and shape. Joint angles were recorded, and digit trajectories were computed using forward kinematics. For a given subject, fingertip trajectories were consistent across trials. The different-sized objects largely produced movement along different portions of a stereotypical trajectory described by a logarithmic spiral. The spirals fit the actual finger positions with a mean error across all trials of 0.23 ± 0.25 cm and accounted for over 98% of the variance in finger position. These patterns were consistent independent of initial finger posture. Subjects did not produce straight-line movements, either in Cartesian space or joint space. The direction of the thumb trajectories exhibited a greater dependence on object type than the finger trajectories, but still utilized a small percentage (<5%) of the available workspace. These results suggest that restoration of a small but specific part of the workspace could have significant impact on function following hand impairment.
Sympathetic Modulation of Acute Cutaneous Flare Induced by Intradermal Injection of Capsaicin in Anesthetized Rats
Authors: Lin Qing , Zou Xiaoju , Fang Li , Willis William D.
Published: May 2006

Much of the acute cutaneous neurogenic inflammation after intradermal injection of capsaicin (CAP) in rats is mediated by dorsal root reflexes (DRRs), which cause the release of inflammatory agents from primary afferent terminals. Sympathetic efferents modulate neurogenic inflammation by interaction with primary afferent terminals. In this study, we examined if DRR-mediated flare after CAP injection is subject to sympathetic modulation. Changes in cutaneous blood flow on the plantar surface of the foot were measured using a laser Doppler flow meter. After CAP injection, cutaneous flare spread more than 20 mm away from the site of CAP injection. However, this CAP-induced flare was significantly reduced after surgical sympathectomy. Decentralization of postganglionic neurons did not affect the flare induced by CAP injection. If the foot of sympathectomized rats was pretreated with an α1-adrenoceptor agonist (phenylephrine) by intra-arterial injection, the spread of flare induced by CAP injection could be restored. However, if the spinal cord was pretreated with a GABAA receptor antagonist, bicuculline, to prevent DRRs, phenylephrine no longer restored the CAP-evoked flare. An α2-adrenoceptor agonist (UK14,304) did not affect the CAP-evoked flare in sympathectomized rats. In sympathetically intact rats, blockade of peripheral α1-adrenoceptors with terazosin profoundly reduced the flare induced by CAP injection, whereas blockade of peripheral α2-adrenoceptors by yohimbine did not obviously affect the flare. Therefore the pathogenesis of acute neurogenic inflammation in the intradermal CAP injection model depends in part on intact sympathetic efferents and α1-adrenoceptors. Peripheral α1-adrenoceptors thus modulate the ability of capsaicin sensitive afferents to evoke the release of inflammatory agents from primary afferents by DRRs.
Neural Activity in Primary Motor and Dorsal Premotor Cortex In Reaching Tasks With the Contralateral Versus Ipsilateral Arm
Authors: Cisek Paul , Crammond Donald J. , Kalaska John F.
Published: May 2006

To investigate the effector dependence of task-related neural activity in dorsal premotor (PMd) and primary motor cortex (M1), directional tuning functions were compared between instructed-delay reaching tasks performed separately with either the contralateral or the ipsilateral limb. During presentation of the instructional cue, the majority (55/90, 61%) of cells in PMd were tuned with both arms, and their dynamic range showed a trend for stronger discharge with the contralateral arm. Most strikingly, however, the preferred direction of most of these latter cells (41/55, 75%) was not significantly different between arms. During movement, many PMd cells continued to be tuned with both arms (53/90, 59%), with a trend for increasing directional differences between the arms over the course of the trial. In contrast, during presentation of the instructional cue only 5/74 (7%) cells in M1 were tuned with both arms. During movement, about half of M1 cells (41/74, 55%) were tuned with both arms but the preferred directions of their tuning functions were often very different and there was a strong bias toward greater discharge rates when the contralateral arm was used. Similar trends were observed for EMG activity. In conclusion, M1 is strongly activated during movements of the contralateral arm, but activity during ipsilateral arm movements is also common and usually different from that seen with the contralateral arm. In contrast, a major component of task-related activity in PMd represents movement in a more abstract or task-dependent and effector-independent manner, especially during the instructed-delay period.
Correlation of Primate Caudate Neural Activity and Saccade Parameters in Reward-Oriented Behavior
Authors: Itoh Hideaki , Nakahara Hiroyuki , Hikosaka Okihide , Kawagoe Reiko , Takikawa Yoriko , Aihara Kazuyuki
Published: May 2006

Changes in the reward context are associated with changes in neuronal activity in the basal ganglia as well as changes in motor outputs. A typical example is found in the caudate (CD) projection neurons and saccade parameters. It raised the possibility that the changes in CD neuronal activity contribute to the changes in saccade parameters. To examine this possibility, we calculated the correlation coefficients (CORs) of the firing rates of each neuron with saccade parameters (peak saccade velocity and latency) on a trial-by-trial basis. We then calculated the mean CORs separately for two CD populations: reward-enhanced type neurons (RENs) that showed enhanced activity and reward-depressed type neurons (RDNs) that showed depressed activity when reward was expected. The activity of RENs was positively correlated with the saccadic peak velocity and negatively correlated with the saccade latency. The activity of RDNs was not significantly correlated with the saccade parameters. We further analyzed the CORs for RENs, a major type of CD neurons. First, we examined the time courses of the CORs using a moving time window (duration: 200 ms). The positive correlation with the saccade velocity and the negative correlation with the saccade latency were present not only in the peri-saccadic period but also during the pre- and postcue periods. Second, we asked whether the CORs with the saccade parameters were direction-selective. A majority of RENs were more active before contralateral saccades (contralateral-preferring neurons) and their activity was correlated more strongly with contralateral saccades than with ipsilateral saccades. A minority of RENs, ipsilateral-preferring neurons, showed no such preference. These results are consistent with the hypothesis that CD neuronal activity exerts facilitatory effects on contralateral saccades and that the effects start well before saccade execution. Furthermore, a multiple regression analysis indicated that changes in activity of some, but not all, CD neurons could be explained by changes in saccade parameters; a major determinant was reward context (presence or absence of reward). These results suggest that, while a majority of CD neurons receive reward-related signals, only some of them can make a significant contribution to change saccadic outputs based on expected reward.
The Anterior Cingulate and Reward-Guided Selection of Actions
Authors: Hadland K. A. , Rushworth M.F.S. , Gaffan D. , Passingham R. E.
Published: May 2006

Macaques were taught a reward-conditional response selection task; they learned to associate each of two different actions to each of two different rewards and to select actions that were appropriate for particular rewards. They were also taught a visual discrimination learning task. Cingulate lesions significantly impaired selection of responses associated with different rewards but did not interfere with visual discrimination learning or performance. The results suggest that 1) the cingulate cortex is concerned with action reward associations and not limited to just detecting when actions lead to errors and 2) that the cingulate cortex's function is limited to action reinforcer associations and it is not concerned with stimulus reward associations.
Role of the Unperturbed Limb and Arms in the Reactive Recovery Response to an Unexpected Slip During Locomotion
Authors: Marigold Daniel S. , Bethune Allison J. , Patla Aftab E.
Published: May 2006

Understanding reactive recovery responses to slipping is fundamental in falls research and prevention. The primary purpose of this study was to investigate the role of the unperturbed limb and arms in the reactive recovery response to an unexpected slip. Ten healthy, young adults participated in this experiment in which an unexpected slip was induced by a set of steel free-wheeling rollers. Surface electromyography (EMG) data were collected from the unperturbed limb (i.e., the swing limb) rectus femoris, biceps femoris, tibialis anterior, and the medial head of gastrocnemius, and bilateral gluteus medius, erector spinae, and deltoids. Kinematic data were also collected by an optical imaging system to monitor limb trajectories. The first slip response was significantly different from the subsequent recovery responses to the unexpected slips, with an identifiable reactive recovery response and no proactive changes in EMG patterns. The muscles of the unperturbed limb, upper body, and arms were recruited at the same latency as those previously found for the perturbed limb. The arm elevation strategies assisted in shifting the center of mass forward after it was posteriorly displaced with the slip, while the unperturbed limb musculature demonstrated an extensor strategy supporting the observed lowering of the limb to briefly touch the ground to widen the base of support and to increase stability. Evidently a dynamic multilimb coordinated strategy is employed by the CNS to control and coordinate the upper and lower limbs in reactive recovery responses to unexpected slips during locomotion.
Blockade of Brain Stem Gap Junctions Increases Phrenic Burst Frequency and Reduces Phrenic Burst Synchronization in Adult Rat
Authors: Solomon Irene C. , Chon Ki H. , Rodriguez Melissa N.
Published: May 2006

Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1–5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 μM), 18α-glycyrrhetinic acid (25–100 μM), 18β-glycyrrhetinic acid (25–100 μM), octanol (200–300 μM), or heptanol (200 μM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (∼95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge ( P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T I ( P < 0.01) and T E ( P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a “bell-shaped” or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (≥130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.
Propagating Wave and Irregular Dynamics: Spatiotemporal Patterns of Cholinergic Theta Oscillations in Neocortex In Vitro
Authors: Bao Weili , Wu Jian-Young
Published: May 2006

Neocortical “theta” oscillation (5–12 Hz) has been observed in animals and human subjects but little is known about how the oscillation is organized in the cortical intrinsic networks. Here we use voltage-sensitive dye and optical imaging to study a carbachol/bicuculline induced theta (∼8 Hz) oscillation in rat neocortical slices. The imaging has large signal-to-noise ratio, allowing us to map the phase distribution over the neocortical tissue during the oscillation. The oscillation was organized as spontaneous epochs and each epoch was composed of a “first spike,” a “regular” period (with relatively stable frequency and amplitude), and an “irregular” period (with variable frequency and amplitude) of oscillations. During each cycle of the regular oscillation, one wave of activation propagated horizontally (parallel to the cortical lamina) across the cortical section at a velocity of ∼50 mm/s. Vertically the activity was synchronized through all cortical layers. This pattern of one propagating wave associated with one oscillation cycle was seen during all the regular cycles. The oscillation frequency varied noticeably at two neighboring horizontal locations (330 μm apart), suggesting that the oscillation is locally organized and each local oscillator is about ≤300 μm wide horizontally. During irregular oscillations, the spatiotemporal patterns were complex and sometimes the vertical synchronization decomposed, suggesting a de-coupling among local oscillators. Our data suggested that neocortical theta oscillation is sustained by multiple local oscillators. The coupling regime among the oscillators may determine the spatiotemporal pattern and switching between propagating waves and irregular patterns.
Distinct Local Circuits Between Neocortical Pyramidal Cells and Fast-Spiking Interneurons in Young Adult Rats
Authors: Angulo María Cecilia , Staiger Jochen F. , Rossier Jean , Audinat Etienne
Published: May 2006

Connections between layer V pyramidal cells and GABAergic fast-spiking interneurons (pyramidal-FS) were studied by paired recordings combined with morphological analyses in acute neocortical slices from 28- to 52-day-old rats. Pairs of spikes elicited in pyramidal cells at a stimulation rate of 0.2 Hz induced unitary excitatory postsynaptic currents (EPSCs) in FS interneurons that displayed facilitation (48%), depression (38.5%), or neither depression nor facilitation (13.5%). Analyses of the EPSC amplitude distributions indicate that depressing connections always showed multiple functional release sites. On the contrary, facilitating connections consisted either of one or several release sites. At a holding potential of −72 mV, the quantal size ( q) and the release probability ( p) of facilitating connections with a single release site were –21.9 ± 7.5 pA and 0.49 ± 0.19 (SD), respectively. The mean q and the estimated number of release sites ( n) at connections showing multiple sites were obtained by decreasing the release probability and did not differ between depressing and facilitating synapses (depressing connections: q = –15.3 ± 2.5 pA, n = 5.1 ± 3, facilitating connections: q = –23.9 ± 9.8 pA, n = 7.8 ± 5.4). However, the quantal content at facilitating synapses with multiple sites (1.9 ± 1.5) was significantly different from that at depressing connections (4.1 ± 3.9). Finally, quantitative morphological analyses revealed that most of the pyramidal cells displaying facilitation can be differentiated from those displaying depression by a more densely branched apical dendritic tree. Therefore two types of morphologically distinct pyramidal cells form excitatory connections with FS interneurons that differ in their short-term plasticity characteristics. Facilitating and depressing connections may provide a differential control of the temporal information processing of FS cells and thus finely regulate the inhibitory effect of these interneurons in neocortical networks of young adult rats.
Distribution of Heterogenic Reflexes Among the Quadriceps and Triceps Surae Muscles of the Cat Hind Limb
Authors: Wilmink Ronnie J. H. , Nichols T. Richard
Published: May 2006

Neural signals from proprioceptors in muscles provide length and force-related linkages among muscles of the limbs. The functions of this network of heterogenic reflexes remain unclear. New data are reported here on the distribution and magnitudes of neural feedback among quadriceps and triceps surae muscles in the decerebrate cat. The purpose of this paper was to distinguish whether inhibitory-force feedback is directed against muscles by virtue of the motor-unit composition or articulation of the muscle. These studies were carried out using controlled stretches and measurements of the resulting force responses of individual quadriceps and triceps surae muscles. Responses were evoked over a wide range of background force levels. In agreement with earlier electrophysiological studies, excitatory length feedback strongly linked the vastus muscles, but excitatory reflexes between each vastus and rectus femoris muscles were weak. We also observed a substantial excitatory linkage from the vastus muscles to the soleus muscle. In contrast, force-related inhibition was absent in the heterogenic reflexes among the vastus muscles but strong and bidirectional between each vastus muscle and the rectus femoris muscle and between triceps surae and quadriceps muscles. We conclude that short-latency feedback in the hindlimb is organized according to muscle articulation. Length feedback within muscle groups regulates joint stiffness while interjoint length feedback may compensate for the effects of nonuniform inertial properties of the limb. Force feedback is organized to regulate coupling between joints and, along with length feedback, determine the mechanical properties of the endpoint.
Vigabatrin Induces Tonic Inhibition Via GABA Transporter Reversal Without Increasing Vesicular GABA Release
Authors: Wu Yuanming , Wang Wengang , Richerson George B.
Published: May 2006

Two forms of GABAergic inhibition coexist: fast synaptic neurotransmission and tonic activation of GABA receptors due to ambient GABA. The mechanisms regulating ambient GABA have not been well defined. Here we examined the role of the GABA transporter in the increase in ambient [GABA] induced by the anticonvulsant vigabatrin. Pretreatment of cultured rat hippocampal neurons with vigabatrin (100 μM) for 2–5 days led to a large increase in ambient [GABA] that was measured as the change in holding current induced by bicuculline during patch-clamp recordings. In contrast, there was a decrease in the frequency of spontaneous miniature inhibitory postsynaptic currents mIPSCs with no change in their amplitude distribution, and a decrease in the magnitude of IPSCs evoked by presynaptic stimulation during paired recordings. The increase in ambient [GABA] was not prevented by blockade of vesicular GABA release with tetanus toxin or removal of extracellular calcium. During perforated patch recordings, the increase in ambient [GABA] was prevented by blocking the GABA transporter, indicating that the GABA transporter was continuously operating in reverse and releasing GABA. In contrast, blocking the GABA transporter increased ambient [GABA] during whole cell patch-clamp recordings unless GABA and Na+were added to the recording electrode solution, indicating that whole cell recordings can lead to erroneous conclusions about the role of the GABA transporter in control of ambient GABA. We conclude that the equilibrium for the GABA transporter is a major determinant of ambient [GABA] and tonic GABAergic inhibition. We propose that fast GABAergic neurotransmission and tonic inhibition can be independently modified and play complementary roles in control of neuronal excitability.
Abl Family Nonreceptor Tyrosine Kinases Modulate Short-Term Synaptic Plasticity
Authors: Moresco Eva Marie Yang , Scheetz Alfred J. , Bornmann William G. , Koleske Anthony J. , Fitzsimonds Reiko Maki
Published: May 2006

Abl family nonreceptor tyrosine kinases regulate cell morphogenesis through functional interactions with the actin cytoskeleton. The vertebrate Abl family kinases, Abl and Arg, are expressed in the adult mouse brain, where they may regulate actin cytoskeletal dynamics in mature neurons. Using immunoelectron microscopy, we have localized Abl and Arg to the pre- and postsynaptic compartments of synapses in the mouse hippocampal area CA1. Paired-pulse facilitation (PPF) was significantly reduced at the Schaffer collateral-CA1 (SC-CA1) excitatory synapses in hippocampal slices from abl−/− and arg−/− mice as compared with wild-type mice. Furthermore, treatment of wild-type slices with the specific Abl family kinase inhibitor STI571 also reduced PPF. Basal synaptic transmission, posttetanic potentiation (PTP), long-term potentiation (LTP), and long-term depression (LTD) were similar to wild-type controls in abl−/− and arg−/− slices and in STI571-treated wild-type slices. These results indicate that an important function of Abl and Arg is to modulate synaptic efficacy via a presynaptic mechanism during repetitive activation.
Temporally Irregular Mnemonic Persistent Activity in Prefrontal Neurons of Monkeys During a Delayed Response Task
Authors: Compte, Albert , Constantinidis Christos , Tegnér Jesper , Raghavachari Sridhar , Chafee Matthew V. , Goldman-Rakic Patricia S. , Wang Xiao-Jing
Published: May 2006

An important question in neuroscience is whether and how temporal patterns and fluctuations in neuronal spike trains contribute to information processing in the cortex. We have addressed this issue in the memory-related circuits of the prefrontal cortex by analyzing spike trains from a database of 229 neurons recorded in the dorsolateral prefrontal cortex of 4 macaque monkeys during the performance of an oculomotor delayed-response task. For each task epoch, we have estimated their power spectrum together with interspike interval histograms and autocorrelograms. We find that 1) the properties of most (about 60%) neurons approximated the characteristics of a Poisson process. For about 25% of cells, with characteristics typical of interneurons, the power spectrum showed a trough at low frequencies (<20 Hz) and the autocorrelogram a dip near zero time lag. About 15% of neurons had a peak at <20 Hz in the power spectrum, associated with the burstiness of the spike train; 2) a small but significant task dependency of spike-train temporal structure: delay responses to preferred locations were characterized not only by elevated firing, but also by suppressed power at low (<20 Hz) frequencies; and 3) the variability of interspike intervals is typically higher during the mnemonic delay period than during the fixation period, regardless of the remembered cue. The high irregularity of neural persistent activity during the delay period is likely to be a characteristic signature of recurrent prefrontal network dynamics underlying working memory.
From Subthreshold to Firing-Rate Resonance
Authors: Richardson Magnus J. E. , Brunel Nicolas , Hakim Vincent
Published: May 2006

First published December 27, 2002; 10.1152/jn.00955.2002. Many types of neurons exhibit subthreshold resonance. However, little is known about whether this frequency preference influences spike emission. Here, the link between subthreshold resonance and firing rate is examined in the framework of conductance-based models. A classification of the subthreshold properties of a general class of neurons is first provided. In particular, a class of neurons is identified in which the input impedance exhibits a suppression at a nonzero low frequency as well as a peak at higher frequency. The analysis is then extended to the effect of subthreshold resonance on the dynamics of the firing rate. The considered input current comprises a background noise term, mimicking the massive synaptic bombardment in vivo. Of interest is the modulatory effect an additional weak oscillating current has on the instantaneous firing rate. When the noise is weak and firing regular, the frequency most preferentially modulated is the firing rate itself. Conversely, when the noise is strong and firing irregular, the modulation is strongest at the subthreshold resonance frequency. These results are demonstrated for two specific conductance-based models and for a generalization of the integrate-and-fire model that captures subthreshold resonance. They suggest that resonant neurons are able to communicate their frequency preference to postsynaptic targets when the level of noise is comparable to that prevailing in vivo.
Projections From Primary Somatosensory Cortex to the Neostriatum: The Role of Somatotopic Continuity in Corticostriatal Convergence
Authors: Hoover John E. , Hoffer Zachary S. , Alloway Kevin D.
Published: May 2006

We characterized the organization of corticostriatal projections from rodent primary somatosensory cortex (SI), testing the hypothesis that projections from SI areas representing subcomponents of the forelimb exhibit greater neostriatal overlap than projections from areas representing separate body parts. The anterograde tracers Fluoro-Ruby (FR), Alexa Fluor (AF), and biotinylated dextran amine (BDA) were injected into physiologically identified regions of rat SI. Injection locations were confirmed by examining the SI barrel fields and limb representations in tangential sections processed for cytochrome oxidase (CO). Experimental animals were divided into two groups: one group received multiple tracer injections in neighboring SI regions that represent separate body parts (whiskers, forepaw, and hindpaw); the other group received injections in SI areas that represent different components of the forelimb (forepaw, antebrachium, and brachium). The distribution of labeled terminals and their varicosities in the neostriatum and in the thalamus were plotted and quantitatively analyzed. For most animals, tracer overlap in the thalamus was either minimal or completely absent. In the neostriatum, projections from the whisker, forelimb, and hindlimb representations terminated in regions that rarely overlap with each other, while those originating from different parts of the forelimb representation were more likely to terminate in overlapping parts of the neostriatum. To the extent that neostriatal activation depends on corticostriatal convergence, the corticostriatal projections in the sensorimotor channel appeared to be organized so that neostriatal neurons may signal when multiple components of the same body part are activated simultaneously.
Spike Frequency Adaptation and Signaling Properties of Identified Neurons in Rodent Deep Spinal Dorsal Horn
Authors: Schneider S. P.
Published: May 2006

Using whole cell recordings, I analyzed the intrinsic discharge properties for 285 neurons in Rexed's laminae III–V of isolated hamster spinal cord preparations. Neurons were characterized by their responses to step-wise and ramp-hold depolarizing current applied through the recording pipettes. Tonic cells (133/285; 47%) fired repetitively during step-wise current application. Firing decayed linearly (–0.14 to –4.3 imp · s–1· s–1) or was bimodal, with an initial exponential phase (τ ≈ 450 ms) followed by a linear decline (–0.02 to –6.3 imp · s–1· s–1); discharge frequency was unrelated to current trajectory. Phasic-firing cells (108/285; 38%) responded with a burst discharge having an initial rapid, exponential decrease (τ ≈ 30 ms) and subsequent linear decline (–1 to –78 imp · s–1· s–1). Phasic cells were activated preferentially by fast current ramps (slope, 70 pA/s–2.2 nA/s) with the number and frequency of impulses increasing with current slope. Delayed-firing cells (44/285; 15%), responded to current steps with an accelerating firing following a substantial latent period (0.5–4 s) and discharged during current ramps with slopes less than ≈100 pA/s. Intracellular staining revealed a significant association between electrophysiological profile and neuronal morphology. A majority of presumed projection cells (22/30; 73%) exhibited tonic firing to step-wise activation. The preponderance of phasic and delayed firing cells, 93% (42/45) and 71% (12/17), respectively, were interneurons with local or intersegmental terminations. Differential sensitivity to static and time-varying components of membrane current suggest differences in neuronal signaling properties that may have important implications for integration of mechanosensory information in the deep spinal dorsal horn.
Nicotinic Receptors on Local Circuit Neurons in Dentate Gyrus: A Potential Role in Regulation of Granule Cell Excitability
Authors: Frazier Charles J. , Strowbridge Ben W. , Papke Roger L.
Published: May 2006

Although the dentate gyrus is one of the primary targets of septo-hippocampal cholinergic afferents, relatively little is known about the cholinergic physiology of neurons in the area. By combining whole cell patch-clamp recording with brief local application of exogenous agonists in horizontal slices, we found that there is robust expression of functional somatic α7-containing nicotinic acetylcholine receptors (nAChRs) on molecular layer interneurons, hilar interneurons, and the glutamatergic mossy cells of the dentate hilus. In contrast, the principal neurons of the dentate gyrus, the granule cells, are generally unresponsive to focal somatic or dendritic application of ACh in the presence of atropine. We also demonstrate that cholinergic activation of α7-containing nAChRs on the subgranular interneurons of the hilus can produce methyllycaconitine-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) in nearby granule cells and enhance the amplitude of an electrically evoked monosynaptic IPSC. Further, activation of α7-containing nAChRs on subgranular interneurons that is timed to coincide with synaptic release of glutamate onto these cells will enhance the functional inhibition of granule cells. These findings suggest that a complex interplay between glutamatergic afferents from the entorhinal cortex and cholinergic afferents from the medial septum could be involved in the normal regulation of granule cell function. Such a relationship between these two afferent pathways could be highly relevant to the study of both age-related memory dysfunction and disorders involving regulation of excitability, such as temporal lobe epilepsy.
Identification of Cerebral Networks by Classification of the Shape of BOLD Responses
Authors: d'Avossa Giovanni , Shulman Gordon L. , Corbetta Maurizio
Published: May 2006

Changes in regional blood oxygen level dependent (BOLD) signals in response to brief visual stimuli can exhibit a variety of time-courses. To demonstrate the anatomical distribution of BOLD response shapes during a match to sample task, a formal analysis of their time-courses is presented. An event-related design was used to estimate regional BOLD responses evoked by a cue word, which instructed the subject to attend to the motion or color of an upcoming target, and those evoked by a briefly presented moving target consisting of colored dots. Regional BOLD time-courses were adequately represented by the linear combination of three orthogonal waveforms. BOLD response shapes were then classified using a fuzzy clustering scheme. Three classes (sustained, phasic, and negative) best characterized cue responses. Four classes (sustained, sustained-phasic, phasic, and bi-phasic) best characterized target responses. In certain regions, the shape of the BOLD responses was modulated by the instruction to attend to the target's motion or color. A left frontal and a posterior parietal region showed sustained activity when motion was cued and transient activity when color was cued. A right thalamic and a left lateral occipital region showed sustained activity when color was cued and transient activity when motion was cued. Following the target several regions showed more sustained activity during motion than color trials. In summary, the effect of the task variable was focal following the cue and widespread following the target. We conclude that the temporal patterns of neural activity affected the shape of the BOLD signal.
Glutamatergic and GABAergic Regulation of Neural Responses in Inferior Colliculus to Amplitude-Modulated Sounds
Authors: Zhang Huiming , Kelly Jack B.
Published: May 2006

Recordings were made from single neurons in the rat inferior colliculus in response to sinusoidally amplitude-modulated sounds (10-s duration) presented to the contralateral ear. Neural responses were determined for different rates of modulation (0.5 Hz to 1 kHz) at a depth of 100%, and modulation transfer functions were generated based on firing rate (MTFFR) and vector strength (MTFVS). The effects of AMPA, NMDA, and GABAA receptor antagonists were examined by releasing drugs iontophoretically through a multibarrel pipette attached to a single-barrel recording pipette. Both the AMPA receptor antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX), and the NMDA receptor antagonist, (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) resulted in a decrease in firing rate, and the GABAA receptor antagonist, bicuculline, produced an increase in the firing rate in most of the cells examined. In some cases, the shape of the MTFFR was modified slightly by receptor antagonists, but in most cases, the peak firing rate that determined a neuron's best modulation frequency remained the same. Also there were no changes during delivery of either excitatory or inhibitory antagonists in the maximum response synchrony at the peak of the MTFVS although some changes were noticed at off-peak modulation rates particularly with the AMPA receptor antagonist, NBQX.