Contralateral Input Research Articles

Detection of Interaural Time Differences in the Alligator

The auditory systems of birds and mammals use timing information from each ear to detect interaural time difference (ITD). To determine whether the Jeffress-type algorithms that underlie sensitivity to ITD in birds are an evolutionarily stable strategy, we recorded from the auditory nuclei of crocodilians, who are the sister group to the birds. In alligators, precisely timed spikes in the first-order nucleus magnocellularis (NM) encode the timing of sounds, and NM neurons project to neurons in the nucleus laminaris (NL) that detect interaural time differences. In vivo recordings from NL neurons show that the arrival time of phase-locked spikes differs between the ipsilateral and contralateral inputs. When this disparity is nullified by their best ITD, the neurons respond maximally. Thus NL neurons act as coincidence detectors. A biologically detailed model of NL with alligator parameters discriminated ITDs up to 1 kHz. The range of best ITDs represented in NL was much larger than in birds, however, and extended from 0 to 1000 micros contralateral, with a median ITD of 450 micros. Thus, crocodilians and birds employ similar algorithms for ITD detection, although crocodilians have larger heads.

Input-selective potentiation and rebalancing of primary sensory cortex afferents by endogenous acetylcholine

Acetylcholine (ACh) plays important roles in the modulation of activity and plasticity of primary sensory cortices, thus influencing sensory detection and integration. We examined this in urethane-anesthetized rats, comparing cholinergic modulation of short latency, large amplitude field postsynaptic potentials (fPSPs) in the visual cortex (V1) evoked by stimulation of the ipsilateral lateral geniculate nucleus (LGN), reflecting direct thalamocortical inputs, with longer latency, smaller amplitude fPSPs elicited by contralateral LGN stimulation, reflecting indirect, polysynaptic inputs. Basal forebrain (BF) stimulation (100 Hz) produced a significant (∼45%), gradually developing potentiation of the smaller, contralateral fPSPs, while ipsilateral fPSPs showed less enhancement (∼15%), shifting the relative strength of dominant/ipsi- and weaker/contralateral inputs to V1. Systemic or local, cortical blockade of muscarinic receptors (scopolamine) reduced potentiation of contralateral fPSP without affecting ipsilateral enhancement, thus preventing the relative amplification of contralateral inputs following BF stimulation. Systemic nicotinic receptor blockade (mecamylamine) resulted in depression of ipsilateral, and reduced enhancement of contralateral fPSPs after BF stimulation. N-methyl-d-aspartate receptor blockade (systemic MK-801) abolished ipsilateral fPSP enhancement without affecting contralateral potentiation. Neither drug reduced the amplification of contralateral relative to ipsilateral signals in V1. In a second experiment in the barrel cortex, BF stimulation enhanced multiunit activity elicited by whisker deflection in a muscarinic-sensitive manner. Similar to the observations in V1, this effect was more pronounced for weaker multiunit activity driven by a surround whisker than activity following principal whisker deflection. These experiments demonstrate that ACh release following BF stimulation exerts surprisingly selective effects to amplify non-dominant inputs to sensory cortices. We suggest that, by diminishing the imbalance between different afferent signals, ACh release during states of behavioral activation acts to induce a long-lasting facilitation of the detection and/or integration of signals in primary sensory fields of the cortical mantle.

A team of potassium channels tunes up auditory neurons

Mammals harbour a diverse array of voltage-gated K+ channels. How those channels team up in a neuron to do a job is becoming clear in the principal cells of the medial nucleus of the trapezoid body (MNTB). Ian Forsythe and his colleagues have used the electrically compact nature of MNTB neurons to measure K+ currents and combined those findings with molecular biological studies to identify, characterize and localize diverse K+ channels on MNTB neurons. A series of reports, the latest by Hardman and Forsythe being in this issue of The Journal of Physiology (Hardman & Forsythe, 2009), show that the firing of action potentials in MNTB neurons is finely controlled by a team of K+ conductances with different properties. Neurons in the MNTB are part of a neuronal circuit that assesses differences in intensity at the two ears, cues that are used to determine where in the horizontal plane sounds arise (Fig. 1A). Neurons in the lateral superior olive (LSO) compare interaural intensity by summing excitation from the ipsilateral ear with inhibition from the contralateral ear. Anyone who has participated in a conversation knows that sounds change rapidly in frequency and intensity; for interaural comparisons of intensity to be useful for localizing sounds, the time of arrival of excitation and inhibition at the LSO must be matched to within a few hundred microseconds. Figure 1 The medial nucleus of the trapezoid body (MNTB) feeds information about contralateral sounds to neurons in the lateral superior olive (LSO) that compare interaural intensity by balancing ipsilateral excitation (red) with contralateral inhibition (blue) ... How are the delays in ipsi- and contralateral inputs to the LSO matched in timing when path from the contralateral ear to the LSO is longer and includes an extra synapse? Neurons from the ipsilateral cochlear nucleus (CN) bring excitation to LSO neurons through relatively fine axons. Globular bushy cells from the contralateral CN, whose axons are particularly large and rapidly conducting, innervate MNTB neurons through calyces of Held. A calyx excites an MNTB neuron with a short and constant synaptic delay, generating large, suprathreshold EPSPs. The team of K+ channels allows MNTB neurons to relay the temporal firing pattern of globular bushy cells to contralateral LSO neurons as precisely timed, glycinergic IPSPs. Which are the members of the team of K+ channels? Voltage-gated K+ channels are formed a tetrameric combinations of α subunits from within a class of channels (e.g. Kv1). Figure 1B summarizes what is known about the presence of various α subunits in the MNTB. (1) Channels of the Kv1 family, located in the pre- and postsynaptic axons as well as on somas of MNTB neurons, provide a prominent, rapidly activating, low-voltage-activated K+ current whose activation around rest shapes synaptic potentials and prevents repetitive firing in both the calyceal terminals and in MNTB neurons (Dodson et al. 2003). (2) Channels that contain Kv2.2 are prominent in the initial segments of axons of MNTB neurons. These high-voltage-activated, slowly activating and deactivating channels hyperpolarize neurons between action potentials when they fire rapidly. In promoting repolarization between action potentials, these channels enhance Na+ currents by removing inactivation when MNTB neurons fire rapidly (Johnston et al. 2008b). (3) Channels containing Kv3.1b mediate a prominent high-voltage-activated, rapidly activating and inactivating K+ current that repolarizes action potentials, making them narrow. Kv3.1b channels are in calyceal terminals as well as on the somatic membranes of MNTB neurons. When they are phosphorylated, Kv3.1b subunits have a lower open probability. Rapid firing induced by electrical stimulation or by a noisy acoustic environment causes a decrease in phosphorylation and an increase in this K+ current (Song et al. 2005). (4) Kv4.3 subunits have been found in the MNTB of mice but not rats (Johnston et al. 2008a). Channels of the Kv4 family mediate A-currents. These K+ currents inactivate rapidly at relatively hyperpolarized potentials making them transient and most evident when depolarization is preceded by hyperpolarization. This small current would be expected to shorten and diminish EPSPs early in a train but becomes inactivated with strong stimulation. (5) Now Hardman and Forsythe show that Kv11 channels encoded by an ether-a-go-go-related gene (ERG) are also present in MNTB neurons of mice. These channels inactivate more rapidly than they activate so that they conduct current mainly upon repolarization after inactivation is removed but before they deactivate. The current through ERG channels repolarizes MNTB neurons, its action being most prominent near the resting potential after a depolarization. K+ channels work as a team to sharpen EPSPs, to sharpen action potentials, and to assure that repolarization removes Na+ inactivation even during rapid firing. K+ channels enable MNTB neurons to fire robustly and to signal with temporal precision even when they are driven at high rates.

Effects of Transient and Prolonged Flashing Light Stimulation on the Cytochrome Oxidase Module System in Layer IV of the Primary Visual Cortex of Kittens

Cytochrome oxidase spots in layer IV of field 17 of the primary visual cortex were studied in kittens aged 33, 49, and 93 days, stimulated with a light flashing at a frequency of 15 Hz. The kittens of one group received stimulation from the moment of eye opening until euthanasia (prolonged stimulation); other groups received stimulation for eight days starting from ages 26, 42, or 85 days (transient stimulation), again until euthanasia. Both types of stimulation were found not to alter the geometrical characteristics of cytochrome oxidase spots, but led to significant increases in the contrast of spots located in the splenial gyrus. Increases in spot contrast in the lateral gyrus occurred only after prolonged stimulation to age 93 days or after transient stimulation from age 26 days to age 33 days. Thus, stimulation of kittens of different ages with a light flashing at a frequency of 15 Hz led to structural-metabolic changes in the primary visual cortex. These changes were apparent to different extents in areas of the cortex responsible for central and peripheral vision. This may be explained, firstly, by the predominant activation of the Y conducting channel of the visual system and, secondly, by the increase in dominance of the contralateral input to the primary visual cortex.

Functional Topography and Integration of the Contralateral and Ipsilateral Retinocollicular Projections ofEphrin-A−/−Mice

Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior-posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in ephrin-A(-/-) mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of ephrin-A(-/-) mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in ephrin-A2(-/-) but disorganized in ephrin-A2/A5(-/-) mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in ephrin-A2/A5(-/-) mice suggests a role for ephrin-As in integrating convergent visual inputs.

Efficient inhibition of bursts by bursts in the auditory system of crickets

In crickets, auditory information about ultrasound is carried bilaterally to the brain by the AN2 neurons. The ON1 neuron provides contralateral inhibitory input to AN2, thereby enhancing bilateral contrast between the left and right AN2s, an important cue for sound localization. We examine how the structures of the spike trains of these neurons affect this inhibitory interaction. As previously shown for AN2, ON1 responds to salient peaks in stimulus amplitude with bursts of spikes. Spike bursts, but not isolated spikes, reliably signal the occurrence of specific features of the stimulus. ON1 and AN2 burst at similar times relative to the amplitude envelope of the stimulus, and bursts are more tightly time-locked to stimulus feature than the isolated spikes. As a consequence, spikes that, in the absence of contralateral inhibition, would occur within AN2 bursts are more likely to be preceded by spikes in ON1 (mainly also in bursts) than are isolated AN2 spikes. This leads to a large decrease in the burst rate of the inhibited AN2. We conclude that the match in coding properties of ON1 and AN2 allows contralateral inhibition to be most efficient for those portions of the response that carry the behaviourally relevant information, i.e. for bursts.

Ipsilateral Hand Input to Area 3b Revealed by Converging Hemodynamic and Electrophysiological Analyses in Macaque Monkeys

Functional magnetic resonance imaging (fMRI) of the hand representation in primary somatosensory cortex (area 3b) of macaque monkeys revealed an ipsilateral hand input undetected by most previous studies. Ipsilateral responses had a hemodynamic signature indistinguishable from that of contralateral hand responses. We explored the neural mechanisms of the fMRI effects using a second derivative analysis of field potentials [current source density (CSD) analysis] combined with action potential profiles, sampled from area 3b using linear array multielectrodes. In contrast to the predominantly excitatory contralateral response, the colocated ipsilateral response appeared dominated by inhibition, suggesting that ipsilateral inputs may have modulatory effects on contralateral input processing. Our findings confirm bimanual convergence at the earliest stage of cortical somatosensory processing in primates. They also illustrate the value of combined CSD and fMRI analyses in monkeys for defining hidden aspects of sensory function and for investigating the neuronal processes generating fMRI signals.

Contralateral Effects and Binaural Interactions in Dorsal Cochlear Nucleus

The dorsal cochlear nucleus (DCN) receives afferent input from the auditory nerve and is thus usually thought of as a monaural nucleus, but it also receives inputs from the contralateral cochlear nucleus as well as descending projections from binaural nuclei. Evidence suggests that some of these commissural and efferent projections are excitatory, whereas others are inhibitory. The goals of this study were to investigate the nature and effects of these inputs in the DCN by measuring DCN principal cell (type IV unit) responses to a variety of contralateral monaural and binaural stimuli. As expected, the results of contralateral stimulation demonstrate a mixture of excitatory and inhibitory influences, although inhibitory effects predominate. Most type IV units are weakly, if at all, inhibited by tones but are strongly inhibited by broadband noise (BBN). The inhibition evoked by BBN is also low threshold and short latency. This inhibition is abolished and excitation is revealed when strychnine, a glycine-receptor antagonist, is applied to the DCN; application of bicuculline, a GABAA-receptor antagonist, has similar effects but does not block the onset of inhibition. Manipulations of discrete fiber bundles suggest that the inhibitory, but not excitatory, inputs to DCN principal cells enter the DCN via its output pathway, and that the short latency inhibition is carried by commissural axons. Consistent with their respective monaural effects, responses to binaural tones as a function of interaural level difference are essentially the same as responses to ipsilateral tones, whereas binaural BBN responses decrease with increasing contralateral level. In comparison to monaural responses, binaural responses to virtual space stimuli show enhanced sensitivity to the elevation of a sound source in ipsilateral space but reduced sensitivity in contralateral space. These results show that the contralateral inputs to the DCN are functionally relevant in natural listening conditions, and that one role of these inputs is to enhance DCN processing of spectral sound localization cues produced by the pinna.

Directionality of the lizard ear

Lizards have highly sensitive ears, but most lizard heads are small (1-2 cm in diameter) compared to the wavelengths of sound of frequencies to which they are most sensitive (1-4 kHz, wavelengths 34-8.5 cm). Therefore, the main cues to sound direction that mammals use - binaural time and intensity cues due to arrival-time differences and sound shadowing by the head--will be very small in lizards. The present work shows that acoustical coupling of the two eardrums in lizards produces the largest directionality of any terrestrial vertebrate ear studied. Laser vibrometric studies of tympanic motion show pronounced directionality within a 1.8-2.4 kHz frequency band around the best frequency of hearing, caused by the interference of ipsi- and contralateral inputs. The results correspond qualitatively to the response of a simple middle ear model, assuming coupling of the tympana through a central cavity. Furthermore, observed directional responses are markedly asymmetrical, with a steep gradient of up to 50-fold (34 dB) response differences between ipsi- and contralateral frontal angles. Therefore, the directionality is easily exploitable by simple binaural subtraction in the brain. Lizard ears are the clearest vertebrate examples of directionality generated by tympanic coupling.

Subtype Composition and Responses of Respiratory Neurons in the Pre-Bötzinger Region to Pulmonary Afferent Inputs in Dogs

The brain stem pre-Botzinger complex (pre-BC) plays an important role in respiratory rhythm generation. However, it is not clear what function each subpopulation of neurons in the pre-BC serves. The purpose of the present studies was to identify neuronal subpopulations of the canine pre-BC and to characterize the neuronal responses of subpopulations to experimentally imposed changes in inspiratory (I) and expiratory (E) phase durations. Lung inflations and electrical stimulation of the cervical vagus nerve were used to produce changes in respiratory phase timing via the Hering-Breuer reflex. Multibarrel micropipettes were used to record neuronal activity and for pressure microejection in decerebrate, paralyzed, ventilated dogs. The pre-BC region was functionally identified by eliciting tachypneic phrenic neural responses to localized microejections of DL-homocysteic acid. Antidromic stimulation and spike-triggered averaging techniques were used to identify bulbospinal and cranial motoneurons, respectively. The results indicate that the canine pre-BC region consists of a heterogeneous mixture of propriobulbar I and E neuron subpopulations. The neuronal responses to ipsi-, contra-, and bilateral pulmonary afferent inputs indicated that I and E neurons with decrementing patterns were the only neurons with responses consistently related to phase duration. Late-I neurons were excited, but most other types of I neurons were inhibited or unresponsive. E neurons with augmenting or parabolic discharge patters were inhibited by ipsilateral inputs but excited by contra- and bilateral inputs. Late-E neurons were more frequently encountered and were inhibited by ipsi- and bilateral inputs, but excited by contralateral inputs. The results suggest that only a limited number of neuron subpopulations may be involved in rhythmogenesis, whereas many neuron types may be involved in motor pattern generation.

Contralateral input modulates the excitability of dorsal horn neurons involved in noxious signal processes. Potential role in neuronal sensitization

Wide Dynamic Range (WDR) neurons in the spinal cord receive inputs from the contralateral side that, under normal conditions, are ineffective in generating an active response. These inputs are effective when the target WDRs change their excitability conditions. To further reveal the mechanisms supporting this effectiveness shift, we investigated the weight of the excitation of the contralateral neurons on the target WDR responses. In the circuit of presynaptic (sending) and postsynaptic (receiving) neurons in crossed spinal connections the fibres that form the presynaptic neurons impinge on postsynaptic neurons can be considered the final relay of this contralateral pathway. The enhancement of the presynaptic neuron excitability may thus modify the efficacy of the contralateral input. Pairs of neurons each on a side of the spinal cord, at the L5–L6 lumbar level were simultaneously recorded in intact, anaesthetized, paralysed rats. The excitatory aminoacid NMDA and strychnine, the antagonist of the inhibitory aminoacid glycine, were iontophoretically administrated to presynaptic neurons to increase their excitability. Before and during the drug administration, spontaneous and noxious-evoked activities of the neurons were analysed. During the iontophoresis of the two substances we found that noxious stimuli applied to the receptive field of presynaptic neurons activated up to 50% of the previously unresponsive postsynaptic neurons on the opposite side. Furthermore, the neurons on both sides of the spinal cord showed significantly increased spontaneous activity and amplified responses to ipsilateral noxious stimulation. These findings indicate that the contralateral input participates in the circuit dynamics of spinal nociceptive transmission, by modulating the excitability of the postsynaptic neurons. A possible functional role of such a nociceptive transmission circuit in neuronal sensitization following unilateral nerve injury is hypothesized.

Morphological and physiological identification of medulla interneurons in the visual system of the tiger beetle larva.

The morphology of visual interneurons in the tiger beetle larva was identified after recording their responses. Stained neurons were designated as either medulla or protocerebral neurons according to the location of their cell bodies. Medulla neurons were further subdivided into three groups. Afferent medulla neurons extended processes distally in the medulla neuropil and a single axon to the brain through the optic nerve. They received their main input from stemmata on the ipsilateral side. Two distance-sensitive neurons, near-by sensitive and far-sensitive neurons, were also identified. Atypical medulla neurons extended their neurites distally in the medulla and proximally to the brain, as afferent medulla neurons, but their input patterns and the shapes of their spikes differed from afferent neurons. Protocerebral neurons sent a single axon to the medulla neuropil. They spread collateral branches in the posterior region of the protocerebrum on its way to the medulla neuropil. They received main input from stemmata on the contralateral side. Medulla intrinsic neurons did not extend an axon to the brain, and received either bilateral or contralateral stemmata input only. The input patterns and discharge patterns of medulla neurons are discussed with reference to their morphology.

Functional glutamatergic and glycinergic inputs to several superior olivary nuclei of the rat revealed by optical imaging

Superior olivary complex (SOC) neurons receive excitatory and inhibitory inputs from both ears. We determined the nature of such inputs to the main SOC nuclei with an optical imaging system. To do so, brainstem slices of postnatal (P) rats (P3–13) were treated with the fast voltage-sensitive dye RH795, and ipsilateral and contralateral SOC inputs were activated electrically. Optical signals, equivalent to membrane potential changes, were detected by a 464-photodiode array. The signals consisted mostly of two components which were identified as pre- and postsynaptic potentials in experiments with Ca 2+-free solutions. They correlated with morphological structures, i.e. the presynaptic components were prominent in neuropil regions whereas the postsynaptic components dominated in somata regions. Postsynaptic components were distinguished pharmacologically with the glycine receptor blocker strychnine and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Concerning the lateral superior olive, we confirmed the known glutamatergic inputs from the ipsilateral side and the glycinergic inputs from the ipsilateral and contralateral sides. Furthermore, we identified a CNQX-sensitive input from the contralateral side. In the medial superior olive, we corroborated the glutamatergic and glycinergic inputs from the ipsilateral and contralateral sides. Both ipsi- and contralaterally, the glutamatergic input was more pronounced than the glycinergic input. In the superior paraolivary nucleus, we also identified ipsilateral and contralateral inputs. Besides the known glycinergic input from the contralateral side, we found a novel glycinergic input from the ipsilateral side and identified CNQX-sensitive inputs from the contralateral and ipsilateral sides. The latter was very weak and appeared only in 30% of the experiments. The data show the feasibility of identifying functional inputs to the SOC with voltage-sensitive dye recordings.

Gabor analysis of auditory midbrain receptive fields: spectro-temporal and binaural composition.

The spectro-temporal receptive field (STRF) is a model representation of the excitatory and inhibitory integration area of auditory neurons. Recently it has been used to study spectral and temporal aspects of monaural integration in auditory centers. Here we report the properties of monaural STRFs and the relationship between ipsi- and contralateral inputs to neurons of the central nucleus of cat inferior colliculus (ICC) of cats. First, we use an optimal singular-value decomposition method to approximate auditory STRFs as a sum of time-frequency separable Gabor functions. This procedure extracts nine physiologically meaningful parameters. The STRFs of approximately 60% of collicular neurons are well described by a time-frequency separable Gabor STRF model, whereas the remaining neurons exhibited obliquely oriented or multiple excitatory/inhibitory subfields that require a nonseparable Gabor fitting procedure. Parametric analysis reveals distinct spectro-temporal tradeoffs in receptive field size and modulation filtering resolution. Comparisons between an identical model used to study spatio-temporal integration areas of visual neurons further shows that auditory and visual STRFs share numerous structural properties. We then use the Gabor STRF model to compare quantitatively receptive field properties of contra- and ipsilateral inputs to the ICC. We show that most interaural STRF parameters are highly correlated bilaterally. However, the spectral and temporal phases of ipsi- and contralateral STRFs often differ significantly. This suggests that activity originating from each ear share various spectro-temporal response properties such as their temporal delay, bandwidth, and center frequency but have shifted or interleaved patterns of excitation and inhibition. These differences in converging monaural receptive fields expand binaural processing capacity beyond interaural time and intensity aspects and may enable colliculus neurons to detect disparities in the spectro-temporal composition of the binaural input.

Processing of interaural temporal disparities in the medial division of the ventral nucleus of the lateral lemniscus.

The medial division of the ventral nucleus of the lateral lemniscus (VNLLm) contains a specialized population of neurons that is sensitive to interaural temporal disparities (ITDs), a potent cue for sound localization along the azimuth. Unlike many ITD-sensitive neurons elsewhere in the auditory system, neurons in the VNLLm respond only at the onset of tones. An onset response may be significant for behavior because, under echoic conditions, tones require sharp onsets for accurate localization. In contrast, noise can generally be localized even with gradual onsets, presumably because transients occur at random intervals in noise. We recorded responses of neurons in the VNLLm to tones and noise in unanesthetized rabbits. We found that although tones elicited a transient response, noise elicited a sustained response as if it was a sequence of transients. The responses to tones indicate that these neurons represent a secondary stage in the processing of ITDs. The onset response to tones was only weakly synchronized to the phase of the tone, indicating that neurons in the VNLLm inherit their sensitivity to ITDs from their inputs. The latencies were short (~8 ms), implying that the ITD sensitivity is derived from ascending inputs. Most neurons in the VNLLm discharged maximally at the same ITD at all frequencies, a characteristic shared with neurons of the medial superior olive. However, the latency of neurons in the VNLLm to interaurally delayed stimuli is linked strongly to the timing of the contralateral stimulus. This suggests that these neurons receive a suprathreshold, contralateral input that is modulated by a subthreshold input conveying information about ITDs. Other stations in the auditory pathway contain a subset of neurons that respond transiently to tones and are sensitive to ITDs. These neurons may represent a novel pathway that assists in localizing sounds in the presence of reflections.

Electrophysiological characterization of the superior paraolivary nucleus in the Mongolian gerbil

The superior paraolivary nucleus (SPN) of the superior olivary complex (SOC) though morphologically well described, has not been characterized physiologically. Here we report the basic response properties of SPN units acquired with extracellular recording techniques under monaural acoustic stimulation in the Mongolian gerbil. Poststimulus-time histograms corresponded to those described earlier for the cat’s cochlear nucleus (onset, chopper, primary-like), and partly to those previously acquired in other SOC nuclei (tonic, off/rebound). Two-thirds of the units responded solely to contralateral stimulation (40% excitatory [E], 19% inhibitory [I], 6% mixed [EI]). Most of the remainder responded equally to stimulation from either ear (18% I.I, 9% E.E). Overall, the monaural contralateral input was more effective than the ipsilateral and bilateral input. Characteristic frequencies and response areas covered the entire hearing range of the gerbil and the units mostly showed broad frequency-tuning. In combination, these properties suggest that the SPN might be a constituent of an afferent pathway encoding stimulus features across broad frequency ranges.

Interaction of Tactile Input in the Human Primary and Secondary Somatosensory Cortex—A Magnetoencephalographic Study

Interaction of simultaneous tactile input at two finger sites in primary (SI) and secondary somatosensory cortex (SII) was studied by whole-head magnetoencephalography. Short pressure pulses were delivered to fingers of the right and left hand at an interstimulus interval of 1.6 s. The first phalanx of the left digit 1 and four other sites were stimulated either separately or simultaneously. We compared four sites with increasing distance: the second phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The temporal evolution of source activity in the contralateral SI and bilateral SII was calculated using spatiotemporal source analysis. Interaction was assessed by comparing the source activity during simultaneous stimulation with the sum of the source activities elicited by separate stimulation. Significant suppressive interaction was observed in contralateral SI only for stimuli at the same hand, decreasing with distance. In SII, all digits of the same and the opposite hand interacted significantly with left digit 1. When stimulating bilaterally, SII source waveforms closely resembled the time course of the response to separate stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation, the contralateral input arriving first in SII appeared to inhibit the later ipsilateral input. Similarly, the separate response to input at two unilateral finger sites which arrived slightly earlier in SII dominated the simultaneous response. Our results confirm previous findings of considerable overlap in the cortical hand representation in SII and illustrate hemispheric specialization to contralateral input when simultaneous stimuli occur bilaterally.

Membrane properties of principal neurons of the lateral superior olive.

In the lateral superior olive (LSO) the firing rate of principal neurons is a linear function of inter-aural sound intensity difference (IID). The linearity and regularity of the "chopper response" of these neurons have been interpreted as a result of an integration of excitatory ipsilateral and inhibitory contralateral inputs by passive soma-dendritic cable properties. To account for temporal properties of this output, we searched for active time- and voltage-dependent nonlinearities in whole cell recordings from a slice preparation of the rat LSO. We found nonlinear current-voltage relations that varied with the membrane holding potential. Repetitive regular firing, supported by voltage oscillations, was evoked by current pulses injected from holding potentials near rest, but the response was reduced to an onset spike of fixed short latency when the pulse was injected from de- or hyperpolarized holding potentials. The onset spike was triggered by a depolarizing transient potential that was supported by T-type Ca(2+)-, subthreshold Na(+)-, and hyperpolarization-activated (I(H)) conductances sensitive, respectively, to blockade with Ni2+, tetrodotoxin (TTX), and Cs+. In the hyperpolarized voltage range, the I(H), was largely masked by an inwardly rectifying K+ conductance (I(KIR)) sensitive to blockade with 200 microM Ba2+. In the depolarized range, a variety of K+ conductances, including A-currents sensitive to blockade with 4-aminopyridine (4-AP) and additional tetraethylammonium (TEA)-sensitive currents, terminated the transient potential and firing of action potentials, supporting a strong spike-rate adaptation. The "chopper response," a hallmark of LSO principal neuron firing, may depend on the voltage- and time-dependent nonlinearities. These active membrane properties endow the LSO principal neurons with an adaptability that may maintain a stable code for sound direction under changing conditions, for example after partial cochlear hearing loss.

Taste laterality in the split brain.

Two patients with corpus callosum resection, one complete and the other sparing the genu and the rostrum, were tested for discrimination of three basic taste stimuli (sour, bitter, salty) applied to the right or left sides of the tongue. Responses were made by pointing with either hand to written words or images of visual objects corresponding to the stimuli, a language-based discrimination. In both patients, response accuracy was significantly above chance for both hemitongues but there was a significant advantage for the left side. Reaction time was shorter for left stimuli than for right stimuli but the difference was not significant. Eight normal controls matched for age with the patients performed equally well with right and left hemitongue stimuli and so did a third callosotomy patient with sparing of the posterior callosum, including the splenium. Tactile and visual tests showed that the left hemisphere was responsible for language-based responses in the first two patients. The results confirm and extend previous findings in another callosotomy patient, indicating that: (i) taste information from either side of the tongue can reach the left hemisphere in the absence of the corpus callosum; (ii) the ipsilateral input from the tongue to the left hemisphere is more potent functionally than the contralateral input and (iii) in the normal brain, the corpus callosum, specifically its posterior part including the splenium, appears to equalize the effects of the ipsilateral and contralateral gustatory inputs on the left hemisphere. Taken together with evidence about lateralized taste deficits following unilateral cortical lesions, the results also suggest that the gustatory pathways from tongue to cortex are bilaterally-distributed with an ipsilateral predominance that may be subject to individual variations.

Bilateral distribution of vagal motor and sensory nerve fibers in the rat's lungs and airways.

This study combined single and transneuronal labeling to define the origin of midline-crossing vagal fibers projecting to the rat's lungs. Injections of the beta-subunit of cholera toxin (CT-beta) into the lungs labeled similar numbers of neuronal somata in the nucleus ambiguus and dorsal motor nucleus of the vagus on both sides of the medulla, even though vagal stimulation increased lung resistance 50% less in the contralateral than in the ipsilateral lung. Unilateral cervical vagotomy prevented CT-beta labeling of ipsilateral neuronal somata and sensory fibers, indicating that lung-bound vagal fibers undergo decussation only inside the thorax. Injections of CT-beta and FluoroGold into opposite main stem bronchi double labeled 30% and 11% of all neuronal somata immunoreactive for CT-beta and FluoroGold, respectively, showing that one single vagal motoneuron can innervate airways on both sides. Injections of pseudorabies virus into the right lung revealed a bilateral network of infected neurons, even after unilateral vagotomy. The latter did not prevent infection of the ipsilateral vagal nuclei. These findings demonstrate that vagal motoneurons that project to the lungs receive contralateral inputs from the airway premotor network and vagal bronchomotor centers.