bluuebunny/crossref_metadata_2025 huggingface dataset:
offResponses in the Auditory Thalamus of the Guinea Pig
Authors: He Jufang
Published: May 2006

on and off auditory responses were examined in the medial geniculate body (MGB) of the guinea pig. Single- and multiunit recordings were carried out on 12 anesthetized animals, and noise-burst or pure-tone stimuli were applied to the ear contralateral to the recording hemisphere. One hundred and thirty-fiveoff or on-off neurons and 160 onneurons were studied, and the tuning curves of 21 on-off oroff neurons were examined from various nuclei of the MGB. The mean minimum threshold of the off responses (40.8 ± 20.0 dB SPL, mean ± SD; range: 0–80 dB SPL) was significantly higher than that of the on responses (28.5 ± 17.6 dB SPL, range: 0–60 dB SPL; n = 17, P < 0.001). Of 10 on-off neurons that showed identifiable tuning frequencies for both on andoff responses, 7 showed a higher off thanon best frequency (BF), 2 showed the same BF for bothon and off, and only 1 showed a slightly loweroff than on BF. Most off responses sampled from the borders of the ventral (MGv) and the rostromedial (MGrm) nuclei of the MGB showed single-peaked tuning curves, similar to those of the on responses in the MGv. The neurons located in the shell (MGs) and dorsal (MGd) nuclei of the MGB showed complicated—either multi-peaked or broad—tuning curves. Alloff responses showed long-duration-selectivity for acoustic stimuli: the mean half-maximum duration was 116.5 ± 114.8 ms ( n = 19, range: 27–411 ms). The latencies of 135off responses were studied in various divisions of the MGB. The ventral border region of MGv showed the shortest latency, followed by the dorsal border region of the MGv, the MGrm, and the caudomedial nucleus (MGcm) of the MGB. The posterior nucleus of the thalamus (Po), the MGd, and the MGs showed much longer mean latencies of >30 ms ( P < 0.05 compared with the border regions of the MGv, ANOVA), with Po showing the greatest mean latency of 60.3 ms and the greatest deviation of 25.5 ms). The latency of the offresponse (29.0 ± 14.0 ms, n = 135) was significantly greater than that of the on response (15.6 ± 9.6 ms, n = 160, P < 0.001). The present results provide valuable information about the threshold, frequency tuning characteristics, minimal response latency, and duration selectivity of off neurons in the auditory thalamus.
Cerebellar Control of Constrained and Unconstrained Movements. I. Nuclear Inactivation
Authors: Goodkin H. P. , Thach W. T.
Published: May 2006

The aim of this study was to determine in monkeys if inactivation of dentate and lateral interposed deep cerebellar nuclei preferentially impairs certain movements relative to others. Constrained movements of the digits were trained with digits, hand, and elbow constrained in a cast. Simplemovements were flexion of Thumb or Index. A compoundmovement was simultaneous flexion of Thumb+Index. An unconstrained movement consisted of a reach to, pinch of, and retrieval of a small food reward (Reach+Pinch). In two monkeys we mapped the dentate and interpositus with 66 injections of muscimol (3 μl of 5 μg/μl). Thirty-two percent of the injections resulted in increased reaction times of Thumb, Index, and Thumb+Index (mean = 24, 24, 28 + 26, respectively). Fifty percent of the injections impaired Reach+Pinch, producing target overshoot, curved reach trajectory, missed target ( X and Y errors), and clumsy pinch with dropped fruit bits. Inactivation impaired each and all of Thumb, Index, Thumb+Index, and Reach+Pinch in 27%, only Reach+Pinch in 23%, and only Thumb, Index, Thumb+Index in 5% of injections. In sum, all types of movement were impaired. Thumb+Index was no more impaired than Thumb orIndex alone, suggesting that the lateral cerebellar nuclei are not specifically required for combining movements of the two digits when constrained. Reach+Pinch appeared so greatly impaired and Thumb, Index, Thumb+Index so little as to be consistent with the hypothesis that a principal role of the cerebellum is to control those interactions that occur between body segments in natural unconstrained movements. However, the fact that all movements were impaired shows that the cerebellum contributes to the control of all movements.
Responses of Primate Visual Cortical Neurons to Stimuli Presented by Flash, Saccade, Blink, and External Darkening
Authors: Gawne Timothy J. , Martin Julie M.
Published: May 2006

Our visual experience constitutes an unending chain of transient events, including those caused by saccadic eye movements, by blinks, and by localized or global changes in the external world. The categorical perception of objects is maintained across different classes of transient events, suggesting that the neural circuitry underlying visual perception responds to different transient events in a similar manner. However, different sorts of transients do have different perceptual impacts: for example, the sudden changes in a scene due to a saccade or a blink do not disturb our perceptual continuity of a visual scene as much as an external change does. We recorded the responses of 103 single visual cortical neurons in two rhesus monkeys (V1: n = 38, V2: n = 19, V3V/VP: n = 30, V4V: n = 16) to the onset and offset of a visual stimulus that was elicited by four different conditions: 1) stimulus flashed on and off while the eyes remain fixed; 2) stimulus turned on and off along with the entire scene (external darkening); 3) stimulus constant, onset and offset induced by rapid saccadic eye movements; and 4) offset induced by an eyeblink. For most neurons the onset and offset of a visual stimulus elicited qualitatively similar responses regardless of condition. We found no systematic effect of different conditions across the neuronal population. Previously we have shown that when the visual scene is occluded by a blink V1 neuronal firing declines in a similar manner as when the external scene is darkened and the eyes left open. Here we show that this is also the case in V2, V3V/VP, and V4V. However, for a substantial minority of neurons, the response varied strongly as a function of the transient event. This overall pattern was the same in all four cortical areas studied here. We hypothesize that most neurons in visual cortex constitute a passive “filter bank”, analyzing the scene for specific details regardless of condition. However, there are neurons that respond in a qualitatively different manner depending on how a stimulus is presented, and we hypothesize that these signals may be important for determining the perceptual salience of a visual event.
Promiscuous and Reversible Blocker of Presynaptic Calcium Channels in Frog and Crayfish Neuromuscular Junctions FromPhoneutria nigriventerSpider Venom
Authors: Troncone Lanfranco R. P. , Georgiou John , Hua Shao-Ying , Elrick Donald , Lebrun Ivo , Magnoli Fabio , Charlton Milton P.
Published: May 2006

Peptide channel blockers found in venoms of many predators are useful pharmacological tools and potential therapeutic agents. The venom of the Brazilian spider Phoneutria nigriventer contains a fraction, ω-phonetoxin-IIA (ω-Ptx-IIA, 8360 MW), which blocks Ca2+channels. At frog neuromuscular junctions (NMJ) bathed in normal Ca2+(1.8 mM) saline, ω-Ptx IIA did not affect spontaneous transmitter release but reversibly reduced evoked transmitter release by 75 and 95% at 12 and 24 nM, respectively. In contrast, toxin effects were irreversible in low-Ca2+(0.5 mM) saline. Ca2+imaging in normal-Ca2+saline showed that ω-Ptx-IIA partially blocked stimulus-dependent presynaptic Ca2+signals, and the blockade was almost completely reversible. Increases in spontaneous release frequency induced by high extracellular K+were blocked by ω-Ptx-IIA. Therefore ω-Ptx-IIA blocks N-type Ca2+channels, which admit Ca2+that triggers transmitter release at the frog NMJ. Additional evidence predicts that ω-Ptx-IIA binds to N-type Ca2+channels at a different site from that of ω-Conotoxin-GVIA. ω-Ptx-IIA also gave a low-affinity partial blockade of transmitter release and presynaptic Ca2+signals at crayfish NMJs where P-type channels are blocked by ω-agatoxin-IVA. The Ca2+-dependent reversibility and promiscuity of this toxin may make it highly useful experimentally and therapeutically.
Inflammation Induces Ectopic Mechanical Sensitivity in Axons of Nociceptors Innervating Deep Tissues
Authors: Bove Geoffrey M. , Ransil Bernard J. , Lin Hsi-Chiang , Leem Jeong-Gill
Published: May 2006

A variety of seemingly diverse pain syndromes are characterized by movement-induced pain radiating in the distribution of a peripheral nerve or nerve root. This could be explained by the induction of ectopic mechanical sensitivity in intact sensory axons. Here we show that inflammation led to mechanical sensitivity of the axons of a subset of mechanically sensitive primary sensory neurons. Dorsal root recordings were made from 194 mechanically sensitive neurons that innervated deep and cutaneous structures and had C, Aδ, and Aαβ conduction velocities. No axons of any category were mechanically sensitive in control experiments. However, the axons of neurons innervating deep structures and having C- or Aδ-conduction velocities became mechanically sensitive during the neuritis, and also exhibited an increased incidence of spontaneous discharge. The incidence of mechanical sensitivity followed a distinct time course. In some cases, paw withdrawal thresholds were obtained after neuritis induction. The time course of the resultant hypersensitivity was not directly related to the time course of the axonal mechanical sensitivity. Ectopic axonal mechanical sensitivity could explain some types of radiating, nerve-related pain coexisting with diseases of seemingly diverse etiologies.
Robustness of the Tuning of Fly Visual Interneurons to Rotatory Optic Flow
Authors: Karmeier Katja , Krapp Holger G. , Egelhaaf Martin
Published: May 2006

The sophisticated receptive field organization of motion-sensitive tangential cells in the visual system of the blowfly Calliphora vicina matches the structure of particular optic flow fields. Hypotheses on the tuning of particular tangential cells to rotatory self-motion are based on local motion measurements. So far, tangential cells have never been tested with global optic flow stimuli. Therefore we measured the responses of an identifiable neuron, the V1 tangential cell, to wide-field motion stimuli mimicking optic flow fields similar to those the fly encounters during particular self-motions. The stimuli were generated by a “planetarium-projector,” casting a pattern of moving light dots on a large spherical projection screen. We determined the tuning curves of the V1-cell to optic flow fields as induced by the animal during 1) rotation about horizontally aligned body axes, 2) upward/downward translation, and 3) a combination of both components. We found that the V1-cell does not respond as specifically to self-rotations, as had been concluded from its receptive field organization. The neuron responds strongly to upward translation and its tuning to rotations is much coarser than expected. The discrepancies between the responses to global optic flow and the predictions based on the receptive field organization are likely due to nonlinear integration properties of tangential neurons. Response parameters like orientation, shape, and width of the tuning curve are largely unaffected by changes in rotation velocity or a superposition of rotational and translational optic flow.
Functional Organization of Parietal Neuronal Responses to Optic-Flow Stimuli
Authors: Merchant Hugo , Battaglia-Mayer Alexandra , Georgopoulos Apostolos P.
Published: May 2006

We analyzed the dissimilarity matrix of neuronal responses to moving visual stimuli using tree clustering and multidimensional scaling (MDS). Single-cell activity was recorded in area 7a while random dots moving coherently in eight different kinds of motion (right-, left-, up-, and downward, clockwise, counterclockwise, expansion, contraction) were presented to behaving monkeys with eyes fixated. Tree clustering analyses showed that the {rightward, leftward}, {upward, downward}, and {clockwise, counterclockwise]} motions were clustered in three separate branches (i.e., horizontal, vertical, and rotatory motion, respectively). In contrast, expansion was in a lone branch, whereas contraction was also separate but within a larger cluster. The distances among these clusters were then subjected to an MDS analysis to identify the dimensions underlying the tree clustering observed. This analysis revealed two major factors in operation. The first factor separated expansion from all other stimulus motions, which seems to reflect the prominence of expansion during the common activity of locomotion. In contrast, the second factor separated planar motions from motion in depth, which suggests that the latter may hold a special place in visual motion processing.
Anesthetic Treatment Blocks Synaptogenesis But Not Neuronal Regeneration of CulturedLymnaeaNeurons
Authors: Woodall Alyson J. , Naruo Hiroaki , Prince David J. , Feng Zhong Ping , Winlow William , Takasaki Mayumi , Syed Naweed I.
Published: May 2006

Trauma and injury necessitate the use of various surgical interventions, yet such procedures themselves are invasive and often interrupt synaptic communications in the nervous system. Because anesthesia is required during surgery, it is important to determine whether long-term exposure of injured nervous tissue to anesthetics is detrimental to regeneration of neuronal processes and synaptic connections. In this study, using identified molluscan neurons, we provide direct evidence that the anesthetic propofol blocks cholinergic synaptic transmission between soma-soma paired Lymnaea neurons in a dose-dependent and reversible manner. These effects do not involve presynaptic secretory machinery, but rather postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover, we discovered that long-term (18–24 h) anesthetic treatment of soma-soma paired neurons blocked synaptogenesis between these cells. However, after several hours of anesthetic washout, synapses developed between the neurons in a manner similar to that seen in vivo. Long-term anesthetic treatment of the identified neurons visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell culture as the neurons continued to exhibit extensive neurite outgrowth. However, these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical (PeA) synapses as observed in their control counterparts. After drug washout, appropriate synapses did reform between the cells, although this synaptogenesis required several days. Taken together, this study provides the first direct evidence that the clinically used anesthetic propofol does not affect nerve regeneration. However, the formation of both chemical and electrical synapses is severely compromised in the presence of this drug. This study emphasizes the importance of short-term anesthetic treatment, which may be critical for the restoration of synaptic connections between injured neurons.
Activation of Peripheral NMDA Receptors Contributes to Human Pain and Rat Afferent Discharges Evoked by Injection of Glutamate into the Masseter Muscle
Authors: Cairns Brian E. , Svensson Peter , Wang Kelun , Hupfeld Steen , Graven-Nielsen Thomas , Sessle Barry J. , Berde Charles B. , Arendt-Nielsen Lars
Published: May 2006

Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and may play a role in deep tissue pain. Injection of the endogenous NMDA receptor agonist glutamate into the masseter muscle excites deep craniofacial afferent fibers in rats and evokes pain in human subjects. It is not clear whether peripheral NMDA receptors play a role in these effects of glutamate. Accordingly, the effect of NMDA on afferent activity as well as the effect of locally administered NMDA receptor antagonists on glutamate-evoked afferent discharges in acutely anesthetized rats and muscle pain in human subjects was examined. Injection of NMDA into the masseter muscle evoked afferent discharges in a concentration-related manner. It was found that the NMDA receptor antagonists 2-amino-5-phosphonvalerate (APV, 10 mM), ketamine (10 mM), and dextromethorphan (40 mM) significantly decreased glutamate-evoked afferent discharges. The effects of APV and ketamine, but not dextromethorphan, were selective for glutamate-evoked afferent discharges and did not affect hypertonic saline-evoked afferent discharges. In human experiments, it was found that 10 mM ketamine decreased glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle pain. These results indicate that injection of glutamate into the masseter muscle evokes afferent discharges in rats and muscle pain in humans in part through activation of peripheral NMDA receptors. It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain.
Dopamine Enhancement of NMDA Currents in Dissociated Medium-Sized Striatal Neurons: Role of D1 Receptors and DARPP-32
Authors: Flores-Hernández Jorge , Cepeda Carlos , Hernández-Echeagaray Elizabeth , Calvert Christopher R. , Jokel Eve S. , Fienberg Allen A. , Greengard Paul , Levine Michael S.
Published: May 2006

Dopamine (DA), via activation of D1 receptors, enhances N-methyl-d-aspartate (NMDA)-evoked responses in striatal neurons. The present investigation examined further the properties of this enhancement and the potential mechanisms by which this enhancement might be effected. Dissociated medium-sized striatal neurons were obtained from intact rats and mice or mutant mice lacking the DA and cyclic adenosine 3′,5′ monophosphate (cAMP)-regulated phosphoprotein of M R 32,000 (DARPP-32). NMDA (10–1,000 μM) induced inward currents in all neurons. In acutely dissociated neurons from intact rats or mice, activation of D1 receptors with the selective agonist, SKF 81297, produced a dose-dependent enhancement of NMDA currents. This enhancement was reduced by the selective D1 receptor antagonist SKF 83566. Quinpirole, a D2 receptor agonist alone, produced small reductions of NMDA currents. However, it consistently and significantly reduced the enhancement of NMDA currents by D1 agonists. In dissociated striatal neurons, in conditions that minimized the contributions of voltage-gated Ca2+ conductances, the D1-induced potentiation was not altered by blockade of L-type voltage-gated Ca2+ conductances in contrast to results in slices. The DARPP-32 signaling pathway has an important role in D1 modulation of NMDA currents. In mice lacking DARPP-32, the enhancement was significantly reduced. Furthermore, okadaic acid, a protein phosphatase 1 (PP-1) inhibitor, increased D1-induced potentiation, suggesting that constitutively active PP-1 attenuates D1-induced potentiation. Finally, activation of D1 receptors produced differential effects on NMDA and gamma aminobutyric acid (GABA)-induced currents in the same cells, enhancing NMDA currents and inhibiting GABA currents. Thus simultaneous activation of D1, NMDA, and GABA receptors could predispose medium-sized spiny neurons toward excitation. Taken together, the present findings indicate that the unique potentiation of NMDA receptor function by activation of the D1 receptor signaling cascade can be controlled by multiple mechanisms and has major influences on neuronal function.
Psychophysical Investigation of an Auditory Spatial Illusion in Cats: The Precedence Effect
Authors: Tollin Daniel J. , Yin Tom C.T.
Published: May 2006

The precedence effect (PE) describes several spatial perceptual phenomena that occur when similar sounds are presented from two different locations and separated by a delay. The mechanisms that produce the effect are thought to be responsible for the ability to localize sounds in reverberant environments. Although the physiological bases for the PE have been studied, little is known about how these sounds are localized by species other than humans. Here we used the search coil technique to measure the eye positions of cats trained to saccade to the apparent locations of sounds. To study the PE, brief broadband stimuli were presented from two locations, with a delay between their onsets; the delayed sound meant to simulate a single reflection. Although the cats accurately localized single sources, the apparent locations of the paired sources depended on the delay. First, the cats exhibited summing localization, the perception of a “phantom” sound located between the sources, for delays < ±400 μs for sources positioned in azimuth along the horizontal plane, but not for sources positioned in elevation along the sagittal plane. Second, consistent with localization dominance, for delays from 400 μs to about 10 ms, the cats oriented toward the leading source location only, with little influence of the lagging source, both for horizontally and vertically placed sources. Finally, the echo threshold was reached for delays >10 ms, where the cats first began to orient to the lagging source on some trials. These data reveal that cats experience the PE phenomena similarly to humans.
Two Distinct Types of Corticothalamic EPSPs and Their Contribution to Short-Term Synaptic Plasticity
Authors: Li Jianli , Guido William , Bickford Martha E.
Published: May 2006

The lateral posterior nucleus (LPN) is innervated by two different morphological types of cortical terminals that originate from cortical layers V and VI. Here we describe two distinct types of excitatory postsynaptic potentials (EPSPs) that were recorded in the LPN after stimulation of corticothalamic fibers. These types of EPSPs differed in amplitude, latency, rise time, and response to increasing levels of stimulus intensity. The most frequently encountered EPSP, type I, displayed a longer latency and slower rise time than the less frequently encountered type II EPSP. Type I EPSPs also showed a graded increase in amplitude with increasing levels of stimulation, whereas type II EPSPs showed an all-or-none response. In response to repetitive stimulation (0.5-20 Hz), type I EPSPs displayed frequency-dependent facilitation, whereas type II EPSPs displayed frequency-dependent depression. Further details of these distinct forms of short-term synaptic plasticity were explored using paired-pulse stimuli. Pharmacology experiments revealed that both N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors are involved in corticothalamic synaptic transmission in the LPN and contribute to both synaptic facilitation and depression. Taken together with the results of our previous anatomical studies, these results suggest that type I EPSPs arise from stimulation of layer VI afferents, whereas type II EPSPs arise from stimulation of layer V inputs. Moreover, type I and II EPSPs in the LPN may be functionally similar to corticogeniculate and retinogeniculate EPSPs, respectively.
Developmental Changes in Evoked Purkinje Cell Complex Spike Responses
Authors: Nicholson Daniel A. , Freeman John H.
Published: May 2006

The development of synaptic interconnections between the cerebellum and inferior olive, the sole source of climbing fibers, could contribute to the ontogeny of certain forms of motor learning (e.g., eyeblink conditioning). Purkinje cell complex spikes are produced exclusively by climbing fibers and exhibit short- and long-latency activity in response to somatosensory stimulation. Previous studies have demonstrated that evoked short- and long-latency complex spikes generally occur on separate trials and that this response segregation is regulated by inhibitory feedback to the inferior olive. The present experiment tested the hypothesis that complex spikes evoked by periorbital stimulation are regulated by inhibitory feedback from the cerebellum and that this feedback develops between postnatal days (PND) 17 and 24. Recordings from individual Purkinje cell complex spikes in urethan-anesthetized rats indicated that the segregation of short- and long-latency evoked complex spike activity emerges between PND17 and PND24. In addition, infusion of picrotoxin, a GABAA-receptor antagonist, into the inferior olive abolished the response pattern segregation in PND24 rats, producing evoked complex spike response patterns similar to those characteristic of younger rats. These data support the view that cerebellar feedback to the inferior olive, which is exclusively inhibitory, undergoes substantial changes in the same developmental time window in which certain forms of motor learning emerge.
Ontogeny of Rhythmic Motor Patterns Generated in the Embryonic Rat Spinal Cord
Authors: Ren Jun , Greer John J.
Published: May 2006

Patterned spontaneous activity is generated in developing neuronal circuits throughout the CNS including the spinal cord. This activity is thought to be important for activity-dependent neuronal growth, synapse formation, and the establishment of neuronal networks. In this study, we examine the spatiotemporal distribution of motor patterns generated by rat spinal cord and medullary circuits from the time of initial axon outgrowth through to the inception of organized respiratory and locomotor rhythmogenesis during late gestation. This includes an analysis of the neuropharmacological control of spontaneous rhythms generated within the spinal cord at different developmental stages. In vitro spinal cord and medullary-spinal cord preparations isolated from rats at embryonic ages (E)13.5–E21.5 were studied. We found age-dependent changes in the spatiotemporal pattern, neurotransmitter control, and propensity for the generation of spontaneous rhythmic motor discharge during the prenatal period. The developmental profile of the neuropharmacological control of rhythmic bursting can be divided into three periods. At E13.5–E15.5, the spinal networks comprising cholinergic and glycinergic synaptic interconnections are capable of generating rhythmic activity, while GABAergic synapses play a role in supporting the spontaneous activity. At late stages (E18.5–E21.5), glutamate drive acting via non- N-methyl-d-aspartate (non-NMDA) receptors is primarily responsible for the rhythmic activity. During the middle stage (E16.5–E17.5), the spontaneous activity results from the combination of synaptic drive acting via non-NMDA glutamatergic, nicotinic acetylcholine, glycine, and GABAAreceptors. The modulatory actions of chloride-mediated conductances shifts from predominantly excitatory to inhibitory late in gestation.
Physiological Response Properties of Neurons in the Superior Paraolivary Nucleus of the Rat
Authors: Kulesza Randy J. , Spirou George A. , Berrebi Albert S.
Published: May 2006

The superior paraolivary nucleus (SPON) is a prominent nucleus of the superior olivary complex. In rats, this nucleus is composed of a morphologically homogeneous population of GABAergic neurons that receive excitatory input from the contralateral cochlear nucleus and inhibitory input from the ipsilateral medial nucleus of the trapezoid body. SPON neurons provide a dense projection to the ipsilateral inferior colliculus and are thereby capable of exerting profound modulatory influence on collicular neurons. Despite recent interest in the structural and connectional features of SPON, little is presently known concerning the physiological response properties of this cell group or its functional role in auditory processing. We utilized extracellular, in vivo recording methods to study responses of SPON neurons to broad band noise, pure tone, and amplitude-modulated pure tone stimuli. Localization of recording sites within the SPON provides evidence for a medial (high frequency) to lateral (low frequency) tonotopic representation of frequencies within the nucleus. Best frequencies of SPON neurons spanned the audible range of the rat and receptive fields were narrow with V-shaped regions near threshold. Nearly all SPON neurons responded at the offset of broad band noise and pure tone stimuli. The vast majority of SPON neurons displayed very low rates of spontaneous activity and only responded to stimuli presented to the contralateral ear, although a small population showed binaural facilitation. Most SPON neurons also generated spike activity that was synchronized to sinusoidally amplitude-modulated tones. Taken together, these data suggest that SPON neurons may serve to encode temporal features of complex sounds, such as those contained in species-specific vocalizations.
Effect of Visual Error Size on Saccade Adaptation in Monkey
Authors: Robinson Farrel R. , Noto Christopher T. , Bevans Scott E.
Published: May 2006

Saccades that consistently over- or undershoot their targets gradually become smaller or larger, respectively. The signal that elicits adaptation of saccade size is a difference between eye and target positions appearing repeatedly at the ends of saccades. Here we describe how visual error size affects the size of saccade adaptation. At the end of each saccade, we imposed a constant-sized error by moving the target to a specified point relative to eye position. We tested a variety of error sizes imposed after saccades to target movements of 6, 12, and 18°. We found that the size of the gain change elicited in a particular experiment depended on both the size of the imposed postsaccade error and on the size of the preceding target movement. For example, imposed errors of 4–5° reduce saccades tracking 6, 12, and 18° target movements by an average of 18, 35, and 45%, respectively. The most effective errors were those that were 15–45% of the size of the initial target eccentricity. Negative errors, which reduce saccade size, were more effective in changing saccade gain than were positive errors, which increased saccade size. For example, for 12° target movements, negative and positive errors of 2–6° changed saccade gain an average of 35 and 8%, respectively. This description of the relationship between error size and adaptation size improves our ability to adapt saccades in the laboratory and characterizes the error sizes that will best drive neurons carrying the adaptation-related visual error signal.
Coding of Horizontal Disparity and Velocity by MT Neurons in the Alert Macaque
Authors: DeAngelis Gregory C. , Uka Takanori
Published: May 2006

We performed the first large-scale ( n = 501), quantitative study of horizontal disparity tuning in the middle temporal (MT) visual area of alert, fixating macaque monkeys. Using random-dot stereograms, we quantified the direction tuning, speed tuning, horizontal disparity tuning, and size tuning of each neuron. The vast majority (93%) of MT neurons were significantly tuned for horizontal disparity. Although disparity tuning was generally quite robust, the average disparity sensitivity of MT neurons was significantly weaker than their direction or speed sensitivity as quantified using both an index of response modulation and an index of signal-to-noise ratio. Disparity tuning was not correlated with direction or size tuning but tended to be broader and weaker for neurons that preferred faster speeds of motion. By comparison with recent studies, we find that disparity selectivity in MT is substantially stronger than that seen in either primary visual cortex (V1) or area V4. In addition, MT neurons are more broadly tuned for disparity than V1 neurons at comparable eccentricities. Disparity tuning curves are very well described by Gabor functions for >80% of MT neurons. The distribution of Gabor phases shows clear bimodality, indicating that MT neurons tend to have odd-symmetric disparity tuning (unlike neurons in V1). The preferred disparities were more strongly correlated with the phase parameter of the Gabor function than with the positional offset parameter. In fact, for neurons with preferred disparities close to zero, the positional offset tended to oppose the phase shift in specifying the disparity preference. We suggest that this result reflects a strategy used to finely distribute the disparity preferences of MT neurons, given the predominance of odd-symmetry and broad tuning.
Regional Analysis of Whole Cell Currents From Hair Cells of the Turtle Posterior Crista
Authors: Brichta Alan M. , Aubert Anne , Eatock Ruth Anne , Goldberg Jay M.
Published: May 2006

The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current ( IK,L), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of IK,Lis slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble IK,L, they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of IK1is rapid and monoexponential, whereas that of Ihis slow and sigmoidal. Many type II cells either have both inward currents or only have IK1; very few cells only have Ih. Inward currents are less conspicuous in type I cells. Type II cells near the torus have smaller outwardly rectifying currents and larger inwardly rectifying currents than those near the planum, but the differences are too small to account for variations in discharge properties of bouton afferents innervating the two regions of the peripheral zone. The large outward conductances seen in central cells, by lowering impedances, may contribute to the low rotational gains of some central-zone afferents.
Reduction of Excitatory Postsynaptic Responses by Persistently Active Metabotropic Glutamate Receptors in the Hippocampus
Authors: Losonczy Attila , Somogyi Peter , Nusser Zoltan
Published: May 2006

The release of glutamate from axon terminals is under the control of a variety of presynaptic receptors, including several metabotropic glutamate receptors (mGluRs). Synaptically released glutamate can activate mGluRs within the same synapse where it was released and also at a distance following its diffusion from the synaptic cleft. It is unknown, however, whether the release of glutamate is under the control of persistently active mGluRs. We tested the contribution of mGluR activation to the excitatory postsynaptic responses recorded from several types of GABAergic interneuron in strata oriens/alveus of the mouse hippocampus. The application of 1 μM (αS)-α-amino-α-[(1S,2S)-2-carboxycyclopropyl]xanthine-9-propanoic acid (LY341495), a broad-spectrum mGluR (subtypes 2/3/7/8) antagonist at this concentration, increased evoked-excitatory postsynaptic current (eEPSC) amplitudes by 60% ( n = 33). On identified cell types, LY341495 had either no effect (7 of 14 basket and 7 of 13 oriens-lacunosum moleculare, O-LM cells) or resulted in a 32 ± 30% (mean ± SD) increase in EPSC amplitudes recorded from basket cells and a seven-times greater (216 ± 102%) enhancement of EPSCs in O-LM cells. The enhancement of the first EPSC of a high-frequency train indicates persistent mGluR activation. During antagonist application, the relative increase in EPSC amplitude evoked by the second and subsequent pulses in the train was not larger than that of the first EPSC, showing no further receptor activation by the released transmitter. The effect of mGluR subtype selective agonists [3 μM L(+)-2-amino-4-phosphonobutyric acid (L-AP4): mGluR4/8; 600 μM L-AP4: mGluR4/7/8; 1 μM (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IU): mGluR2/3] and an antagonist (0.2 μM LY341495: mGluR2/3/8) suggests that persistently active mGluR2/3/8 control the excitability of hippocampal network.
Differential Changes in Signal and Background Firing of Accumbal Neurons During Cocaine Self-Administration
Authors: Peoples Laura L. , Cavanaugh Daniel
Published: May 2006

Learning theories of drug addiction propose that the disorder is, at least in part, attributable to drug effects on accumbal mechanisms that are normally involved in reward-related learning. The neurophysiological mechanisms that might transduce such a drug effect on accumbal mechanisms have yet to be identified. Previous studies showed that a population of accumbal neurons exhibit phasic excitatory responses time locked to cocaine-reinforced lever presses during intravenous cocaine self-administration sessions (neurons referred to as lever-press neurons). Most of the same neurons, like the majority of accumbal neurons, also show a decrease in average firing rate during the drug self-administration session. Evidence indicates that the phasic firing patterns transmit information related to drug-reward-related events. On the other hand, the decreases in average firing reflect a primary pharmacological effect of self-administered cocaine. In the present study, we tested the hypothesis that the phasic firing associated with drug seeking (i.e., signal) is less sensitive than other accumbal firing (i.e., background) to the inhibitory effect of cocaine. During intravenous cocaine self-administration sessions, 45 of 68 neurons showed a decrease in average firing during the self-administration session relative to a predrug baseline period. Fourteen neurons showed both an inhibition in average firing and an excitatory phasic response. For these 14 neurons, signal either remained equal to the average predrug firing rate or exceeded the predrug firing rate during the self-administration session. For the same neurons, background firing generally fell below average predrug firing. The differential changes in signal and background were associated with an increase in the ratio of signal-to-background for the individual neurons. Moreover, the relatively unique resistance of signal to inhibition was associated with an increase in the ratio of signal firing of all lever-press neurons relative to the background firing of all recorded neurons. This type of differential inhibition in signal and background firing might be expected to increase the relative influence of the drug-reward-related signals on accumbal-related neural circuits and differentially influence susceptibility of drug- and non-drug-reward-related synaptic and neural responses to neuroplasticity. It thus represents a mechanism by which inhibitory effects of self-administered drug might amplify the accumbal contribution to behavior and learning and potentially contribute to drug addiction.
Quantitative Comparison Between Functional Imaging and Single-Unit Spiking in Rat Somatosensory Cortex
Authors: Masino Susan A.
Published: May 2006

The profile of activity across rat somatosensory cortex on stimulation of a single whisker was examined using both intrinsic signal imaging and electrophysiological recording. In the same animals, under sodium pentobarbital anesthesia, the intrinsic signal response to a 5-Hz stimulation of whisker C2 was recorded through a thinned skull. Subsequently, the thinned skull was removed, and individual cortical neurons were recorded at multiple locations and in all cortical layers in response to the same whisker stimulation paradigm. The amplitude of the evoked response obtained with both techniques was quantified across the cortical surface with respect to distance (≤1.6 mm) from the peak intrinsic signal activity. Cortical neurons were rated as having a significant or nonsignificant whisker-evoked response as compared with a baseline period of spontaneous firing; a minority of neurons exhibited a small but significant increase in neuronal spiking even at long distances (>1.6 mm) from the optically determined peak of activity. Overall, this analysis shows a significant correlation between the two techniques in terms of the profile of evoked activity across the cortical surface. Furthermore, this data set affords a detailed and quantitative comparison between the two activity-dependent techniques—one measuring an intrinsic decrease in light reflectance based largely on metabolic changes and one measuring neuronal firing patterns. Studies such as this, comparing directly between imaging and detailed electrophysiology, may influence the interpretation of the extent of the activated area as assessed with in vivo functional imaging techniques.
Spike-Dependent GABA Inputs to Bipolar Cell Axon Terminals Contribute to Lateral Inhibition of Retinal Ganglion Cells
Authors: Shields Colleen R. , Lukasiewicz Peter D.
Published: May 2006

The inhibitory surround signal in retinal ganglion cells is usually attributed to lateral horizontal cell signaling in the outer plexiform layer (OPL). However, recent evidence suggests that lateral inhibition at the inner plexiform layer (IPL) also contributes to the ganglion cell receptive field surround. Although amacrine cell input to ganglion cells mediates a component of this lateral inhibition, it is not known if presynaptic inhibition to bipolar cell terminals also contributes to surround signaling. We investigated the role of presynaptic inhibition by recording from bipolar cells in the salamander retinal slice. TTX reduced light-evoked GABAergic inhibitory postsynaptic currents (IPSCs) in bipolar cells, indicating that presynaptic pathways mediate lateral inhibition in the IPL. Photoreceptor and bipolar cell synaptic transmission were unaffected by TTX, indicating that its main effect was in the IPL. To rule out indirect actions of TTX, we bypassed lateral signaling in the outer retina by either electrically stimulating bipolar cells or by puffing kainate (KA) directly onto amacrine cell processes lateral to the recorded cell. In bipolar and ganglion cells, TTX suppressed laterally evoked IPSCs, demonstrating that both pre- and postsynaptic lateral signaling in the IPL depended on action potentials. By contrast, locally evoked IPSCs in both cell types were only weakly suppressed by TTX, indicating that local inhibition was not as dependent on action potentials. Our results show a TTX-sensitive lateral inhibitory input to bipolar cell terminals, which acts in concert with direct lateral inhibition to give rise to the GABAergic surround in ganglion cells.
Binding Sites, Singly Bound States, and Conformation Coupling Shape GABA-Evoked Currents
Authors: Mozrzymas Jerzy W. , Barberis Andrea , Mercik Katarzyna , Z˙arnowska Ewa D.
Published: May 2006

The time course of GABA-evoked currents is the main source of information on the GABAAreceptor gating. Since the kinetics of these currents depends on the transitions between several receptor conformations, it is a major challenge to define the relations between current kinetics and the respective rate constants of the microscopic gating scheme. The aim of this study was to further explore the impact of different GABAA receptor conformations on the kinetics of currents elicited by ultra-fast GABA applications. We show that the rising phase and amplitude of GABA-evoked currents depend on desensitization and singly bound states. The occupancy of bound receptors depends not only on binding properties but also on opening/closing and desensitization. The impact of such functional coupling between channel states is critical in conditions of high non-equilibrium typical for synaptic transmission. The concentration dependence of the rising phase of the GABA-elicited current indicates positive cooperativity between agonist binding sites. We provide evidence that preequilibration at low GABA concentrations reduce GABA-evoked currents due to receptor trapping in a singly bound desensitized state.
Nonspiking and Spiking Proprioceptors in the Crab: White Noise Analysis of Spiking CB-Chordotonal Organ Afferents
Authors: Gamble E. Rolland , DiCaprio Ralph A.
Published: May 2006

The proprioceptors that signal the position and movement of the first two joints of crustacean legs provide an excellent system for comparison of spiking and nonspiking (graded) information transfer and processing in a simple motor system. The position, velocity, and acceleration of the first two joints of the crab leg are monitored by both nonspiking and spiking proprioceptors. The nonspiking thoracic-coxal muscle receptor organ (TCMRO) spans the TC joint, while the coxo-basal (CB) joint is monitored by the spiking CB chordotonal organ (CBCTO) and by nonspiking afferents arising from levator and depressor elastic strands. The response characteristics and nonlinear models of the input-output relationship for CB chordotonal afferents were determined using white noise analysis (Wiener kernel) methods. The first- and second-order Wiener kernels for each of the four response classes of CB chordotonal afferents (position, position-velocity, velocity, and acceleration) were calculated and the gain function for each receptor determined by taking the Fourier transform of the first-order kernel. In all cases, there was a good correspondence between the response of an afferent to deterministic stimulation (trapezoidal movement) and the best-fitting linear transfer function calculated from the first-order kernel. All afferents also had a nonlinear response component and second-order Wiener kernels were calculated for afferents of each response type. Models of afferent responses based on the first- and second-order kernels were able to predict the response of the afferents with an average accuracy of 86%.
Nonspiking and Spiking Proprioceptors in the Crab: Nonlinear Analysis of Nonspiking TCMRO Afferents
Authors: DiCaprio Ralph A.
Published: May 2006

The proprioceptor that signals the position and movement of the first joint of crustacean legs provides an excellent system for investigating information processing and transmission in neurons that function in a graded (nonspiking) manner in the context of a simple motor system. The thoracic-coxal muscle receptor organ (TCMRO) spans the thoracic-coxal joint and transmits graded signals to the CNS via two large nonspiking axons. The response characteristics and nonlinear models of the input-output relationship for the two nonspiking TCMRO afferents (S and T fibers) were determined using white noise analysis (Wiener kernel) methods. The best-fitting linear responses of these neurons was similar, as were their second-order kernels. The gains of the afferents slowly increased with increasing frequency and reached a maximum at approximately 40–60 Hz for the S fiber and 60–80 Hz for the T fiber. Above this corner frequency, the gains of both afferents decreased at approximately 20 dB/decade for the remainder of the 220-Hz stimulus bandwidth. The shape of the first-order kernels, and hence the corresponding (linear) gain functions, of both afferents were similar when driven with different amplitudes of noise, covering a 40-fold amplitude range. Predictions of the S fiber response based on the first two Wiener kernels were accurate, with the second-order model producing a mean square error of 6–8%. Second-order Wiener models for the T fiber were less accurate with a mean square error of approximately 22–26%, but this accuracy improved to 10–16% with the incorporation of the third-order term in the Wiener expansion. The effect of cable properties on the transmission of the sensory potentials to the CNS was evaluated by determining the system characteristics using membrane potentials 5–7 mm distal to the transduction site. The major change after transmission along the axon was a low-pass filtering of the sensory signals and consequent reduction in signal bandwidth.