Age-related alteration in processing of temporal sound features in the auditory midbrain of the CBA mouse

The perception of complex sounds, such as speech and animal vocalizations, requires the central auditory system to analyze rapid, ongoing fluctuations in sound frequency and intensity. A decline in temporal acuity has been identified as one component of age-related hearing loss. The detection of short, silent gaps is thought to reflect an important fundamental dimension of temporal resolution. In this study we compared the neural response elicited by silent gaps imbedded in noise of single neurons in the inferior colliculus (IC) of young and old CBA mice. IC neurons were classified by their temporal discharge patterns. Phasic units, which accounted for the majority of response types encountered, tended to have the shortest minimal gap thresholds (MGTs), regardless of age. We report three age-related changes in neural processing of silent gaps. First, although the shortest MGTs (1-2 msec) were observed in phasic units from both young and old animals, the number of neurons exhibiting the shortest MGTs was much lower in old mice, regardless of the presentation level. Second, in the majority of phasic units, recovery of response to the stimulus after the silent gap was of a lower magnitude and much slower in units from old mice. Finally, the neuronal map representing response latency versus best frequency was found to be altered in the old IC. These results demonstrate a central auditory system correlate for age-related decline in temporal processing at the level of the auditory midbrain.     

Evidence for an across-frequency, between-channel process in asymptotic monaural temporal gap detection

Monaurally measured temporal gap detection (TGD) thresholds characteristically increase as the frequency difference is increased over a range of about half an octave to an octave between two sinusoids that mark the onset and offset of the silent gap. For greater sinusoidal frequency separations, the TGD thresholds often become asymptotic. This pattern probably reflects two different processes. The first process likely reflects within-channel processing within a single auditory filter or channel. The second process is less certain, but may reflect between-channel processing of the silent gap stimulus across two or more independent frequency channels. To evaluate the hypothesis that asymptotic monaural gap detection can be explained by a simple between-channel process, TGD thresholds were measured as a function of frequency separation between a pregap sinusoid presented to the left ear (channel 1) and a postgap sinusoid, of higher frequency, presented to the right ear (channel 2). The rationale for dichotic presentation of the sinusoidal markers and gap signal followed from the fact that the gap detection task must be performed between two independent channels by combining the outputs from each channel (ear) and recovering the gap information centrally. The resulting TGD thresholds for pregap sinusoids from 250 to 4000 Hz were relatively invariant and increased only slightly with increasing marker frequency separation. The average TGD thresholds for four listeners were in the range of 30 to 40 ms, which corresponded closely with their asymptotic TGD thresholds for the same set of stimulus conditions measured monaurally. This correspondence of the two data sets supports an across-frequency, between-channel process for asymptotic monaural gap detection at marker frequency separations greater than about half an octave.     

Inputs from three brainstem sources to identified neurons of the mouse inferior colliculus slice

A total of 40 neurons from of the central nucleus of the mouse inferior colliculus (IC) were recorded intracellularly from brain slices to determine input properties by electrical stimulation of the ipsilateral lateral lemniscus (LL), commissure of Probst (CP), and commissure of the IC (CoIC) together with cellular morphology (in 25 neurons) by biocytin injection and staining. Nine neurons had oriented (bipolar), 16 neurons non-oriented (multipolar) dendritic trees of various sizes. Axon collaterals of a given neuron often ran in several directions to provide multiple input to adjacent isofrequency laminae, the lateral nucleus of the IC, the brachium of the IC, the LL, the CP, and the IC commissure. Neurons were classified by spike response patterns to depolarizing current injection into onset- and sustained-spiking cells. The former had significantly shorter membrane-time constants, significantly less frequently and smaller hyperpolarizations after spike occurrence, and more Ca2+-humps. These properties and their preferred position in the dorsolateral ICC suggest a participation in binaural temporal processing. Almost all oriented cells showed only excitatory post-synaptic potentials (EPSPs) after LL stimulation, while in non-oriented cells inhibitory post-synaptic potentials (IPSPs) after the EPSPs were significantly more frequent. Neurons with largest dendritic trees and many dorsalward projecting axon collaterals were found in the ventral IC. There, neurons had average 4 ms (two synapses) shorter response latencies to LL stimulation than dorsally located neurons. Thus, neurons in the central and dorsal IC may receive mono- and disynaptic input from ventrally located neurons.     

Detection of silent intervals between noises activating different perceptual channels: some properties of "central" auditory gap detection

This article describes four experiments on gap detection by normal listeners, with the general goal being to examine the consequences of using noises in different perceptual channels to delimit a silent temporal gap to be detected. In experiment 1, subjects were presented with pairs of narrow-band noise sequences. The leading element in each pair had a center frequency of 2 kHz and the trailing element's center frequency was parametrically varied. Gap detection thresholds became increasingly poor, sometimes by up to an order of magnitude, as the spectral disparity was increased between the noise bursts that marked the gap. These data suggested that gap-detection performance is impoverished when the underlying perceptual timing operation requires a comparison of activity in different perceptual channels rather than a discontinuity detection within a given channel. In experiment 2, we assessed the effect of leading-element duration in within-channel and between-channel gap detection tasks. Gap detection thresholds rose when the duration of the leading element was less than about 30 ms, but only in the between-channel case. In experiment 3, the gap-detection stimulus was redesigned so that we could probe the perceptual mechanisms that might be involved in stop consonant discrimination. The leading element was a wideband noise burst, and the trailing element was a 300-ms bandpassed noise centered on 1.0 kHz. The independent variable was the duration of the leading element, and the dependent variable was the smallest detectable gap between the elements. When the leading element was short in duration (5-10 ms), gap thresholds were close to 30 ms, which is close to the voice onset time that parses some voiced from unvoiced stop consonants. In experiment 4, the generality of the leading-element duration effect in between-channel gap detection was examined. Spectrally identical noises defining the leading and trailing edges of the gap were presented to the same or to different ears. There was a leading-element duration effect only for the between channel case. The mean gap threshold was again close to 30 ms for short leading-element durations. Taken together, the data suggest that gap detection requiring a temporal correlation of activity in different perceptual channels is a fundamentally different task to the discontinuity detection used to execute gap detection performance in the traditional, within-channel paradigm.     

Physiology of the young adult Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli

This study was designed to establish the young adult (3 month) Fischer 344 (F344) rat as a model of inferior colliculus (IC) physiology, providing a baseline for analysis of changes in single unit responses as the animals age and for the study of noise induced hearing loss. The response properties of units localized to the central nucleus of the IC (CIC) and those localized to the external cortex of the IC (ECIC) were compared in order to better characterize differences between these two subnuclei in the processing of simple auditory stimuli. In vivo extracellular single unit recordings were made from IC neurons in ketamine/xylazine anesthetized young adult F344 rats. When a unit was electrically isolated, the spontaneous activity level, characteristic frequency (CF) and CF threshold were determined. Rate/intensity functions (RIFs) in response to contralateral CF tones and to contralateral noise bursts were obtained as were tone isointensity functions. The recording site was marked by ejecting horseradish peroxidase (HRP) from an electrode. Locations of recorded units were determined from electrode track marks and HRP marks in serial brain sections. Recordings were made from 320 neurons in the IC; 176 were localized to the CIC and 87 to the ECIC. Thirteen percent of the units in each subdivision were found to be poorly responsive to auditory stimulation (clicks, tones or noise), and spontaneous activity was generally low. Characteristic frequencies representative of the full rat audiogram were found in each subdivision with the mean threshold significantly higher in the ECIC (28.7 dB SPL) than in the CIC (22.3 dB SPL). The mean maximum discharge rate to CF tone bursts was near 24 spikes/s in each subdivision. Dynamic range tended to be higher in the ECIC (28.3 dB) than in the CIC (23.2 dB), reflecting the lower percentage of nonmonotonic units found in the ECIC. Most units responded more robustly with a slower tone presentation rate, displayed lower levels of discharge to noise bursts than to tone bursts, and had differently shaped tone and noise RIFs. Most units were classified as onset responders to CF tone bursts in both subdivisions, with the percentage of onset responders higher in the ECIC (68.9%) than in the CIC (57.8%). First spike latency did not differ significantly between the subdivisions, but tended to be shorter in the CIC. The breadth of the excitatory receptive fields did not differ significantly between subdivisions, although the mean was slightly larger in the ECIC. These results are generally consistent with the results of CIC studies from other species, establishing the F344 rat as a model of CIC physiology. Differences between CIC and ECIC units included a higher percentage of nonmonotonic RIFs and lower percentage of onset temporal response patterns in the CIC than in the ECIC. Some properties which have been previously used as hallmarks for differentiation between CIC and ECIC units, namely broader tuning and longer first spike latencies in the ECIC, did not reach statistical significance in this study. These may reflect species differences and/or the highly variable and largely overlapping sets of responses evident in the large sample size used in this study.     

Age-related decline in auditory plasticity: Experience dependent changes in gap detection as measured by prepulse inhibition in young and aged rats.

Young adult and aged F344 rats were compared on a silent gap variant of the prepulse inhibition paradigm. Animals were tested using a 50-ms single tone cue, followed by 8 days of silent gap testing. The first 3 days of gap testing were long gaps (range 2 to 100 ms) followed by 5 days of short gaps (range 2 to 10 ms). The effects of gap length, prior experience, and age, on the magnitude and direction (facilitation vs. attenuation) of the acoustic startle response, were examined. The young rats showed stronger and more reliable acoustic startle responses (uncued trials) during all acoustic startle tasks as compared to the old. The younger animals also exhibited a more consistent attenuated response across cues and days. Depending on silent gap length, both reduction (inhibition) and enhancement (facilitation) of startle were observed. Finally, only the young adult animals showed an experience-related shift from facilitation to attenuation in response to very short silent gap cues, and this initial early facilitation predicted later attenuation following additional experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal encoding of sound direction in the auditory midbrain of the rainbow trout

Acoustical stimulation causes displacement of the sensory hair cells relative to the otoliths of the fish inner ear. The swimbladder, transforming the acoustical pressure component into displacement, also contributes to the displacement of the hair cells. Together, this (generally) yields elliptical displacement orbits. Alternative mechanisms of fish directional hearing are proposed by the phase model, which requires a temporal neuronal code, and by the orbit model, which requires a spike density code. We investigated whether the directional selective response of auditory neurons in the midbrain torus semicircularis (TS; homologous to the inferior colliculus) is based on spike density and/or temporal encoding. Rainbow trout were mounted on top of a vibrating table that was driven in the horizontal plane to simulate sound source direction. Rectilinear and elliptical (or circular) motion was applied at 172 Hz. Generally, responses to rectilinear and elliptical/circular stimuli (irrespective of direction of revolution) were the same. The response of auditory neurons was either directionally selective (DS units, n = 85) or not (non-DS units, n = 106). The average spontaneous discharge rate of DS units was less than that of non-DS units. Most DS units (70%) had spontaneous activities < 1 spike per second. Response latencies (mode at 18 ms) were similar for both types of units. The response of DS units is transient (19%), sustained (34%), or mixed (47%). The response of 75% of the DS units synchronized to stimulus frequency, whereas just 23% of the non-DS responses did. Synchronized responses were measured at stimulus amplitudes as low as 0.5 nm (at 172 Hz), which is much lower than for auditory neurons in the medulla of the trout, suggesting strong convergence of VIIIth nerve input. The instant of firing of 42% of the units was independent of stimulus direction (shift <15 degrees), but for the other units, a direction dependent phase shift was observed. In the medial TS spatial tuning of DS units is in the rostrocaudal direction, whereas in the lateral TS all preferred directions are present. On average, medial DS units have a broader directional selectivity range, are less often synchronized, and show a smaller shift of the instant of firing as a function of stimulus direction than lateral DS units. DS response characteristics are discussed in relation to different hypotheses. We conclude that the results are more in favor of the phase model.     

Effect of flow on first-pass metabolism of drugs: single pass studies on 4-methylumbelliferone conjugation in the serially perfused rat intestine and liver preparations

Intracellular in vivo recordings of physiologically identified inferior colliculus central nucleus (ICc) auditory neurons (n = 71) were carried out in anesthetized guinea pigs. The neuronal membrane characteristics are described showing mainly quantitative differences with a previous report [Nelson, P.G. and Erulkar, S.D., J. Neurophysiol., 26 (1963) 908-923]. The spontaneous spike activity was consistent with the discharge pattern of most extracellularly recorded units. The action potentials showed different spike durations, short and long, and some of them exhibited hyperpolarizing post-potentials. There were also differences in firing rate. The ICc neurons exhibited irregular activity producing spike trains as well as long silent periods (without spikes). Intracellular current injection revealed membrane potential adaptation and shifts that outlasted the electrical stimuli by 20-30 ms. Both evoked synaptic potentials and the spike activity in response to click and tone-burst stimulation were analyzed. Depolarizing-hyperpolarizing synaptic potentials were found in response to contralateral and binaural sound stimulation that far outlasted the stimulus (up to 90 ms). When ipsilaterally stimulated, inhibitory responses and no-responses were also recorded. Although few cells were studied, a similar phenomenon was observed using tone-burst stimulation; moreover, a good correlation was obtained between membrane potential shifts and the triggered spikes (input-output relationship). These in vivo results demonstrate the synaptic activity underlying many of the extracellularly recorded discharge patterns. The data are consistent with the known multi-synaptic ascending pathway by which signals arrive at the ICc as well as the descending corticofugal input that may contribute to the generation of long duration post-synaptic potentials.     

The adequate stimulus for avian short latency vestibular responses to linear translation

Transient linear acceleration stimuli have been shown to elicit eighth nerve vestibular compound action potentials in birds and mammals. The present study was undertaken to better define the nature of the adequate stimulus for neurons generating the response in the chicken (Gallus domesticus). In particular, the study evaluated the question of whether the neurons studied are most sensitive to the maximum level of linear acceleration achieved or to the rate of change in acceleration (da/dt, or jerk). To do this, vestibular response thresholds were measured as a function of stimulus onset slope. Traditional computer signal averaging was used to record responses to pulsed linear acceleration stimuli. Stimulus onset slope was systematically varied. Acceleration thresholds decreased with increasing stimulus onset slope (decreasing stimulus rise time). When stimuli were expressed in units of jerk (g/ms), thresholds were virtually constant for all stimulus rise times. Moreover, stimuli having identical jerk magnitudes but widely varying peak acceleration levels produced virtually identical responses. Vestibular response thresholds, latencies and amplitudes appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes such as peak acceleration or rise time alone do not provide sufficient information to predict response parameter quantities. Indeed, the major response parameters were shown to be virtually independent of peak acceleration levels or rise time when these stimulus features were isolated and considered separately. It is concluded that the neurons generating short latency vestibular evoked potentials do so as "jerk encoders" in the chicken. Primary afferents classified as "irregular", and which traditionally fall into the broad category of "dynamic" or "phasic" neurons, would seem to be the most likely candidates for the neural generators of short latency vestibular compound action potentials.     

Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice with the aim of extending the classification of inspiratory neurons to include analysis of active membrane properties. 2. The slice generated a regular rhythmic motor output recorded as burst of action potentials on a XII nerve root with a peak to peak time of 11.5 +/- 3.4 s and a duration of 483 +/- 54 ms (means +/- SD, n = 50). Based on the electroresponsive properties and membrane potential trajectories throughout the respiratory cycle, three types of inspiratory neurons could be distinguished. 3. Type-1 neurons were spiking in the interval between the inspiratory potentials (n = 9) or silent with a resting membrane potential of -48.6 +/- 10.1 mV and an input resistance of 306 +/- 130 M omega (n = 15). The spike activity between the inspiratory potentials was burst-like with spikes riding on top of an underlying depolarization (n = 11) or regular with no evidence of bursting (n = 12). Hyperpolarization of the neurons below threshold for spike initiation did not reveal any underlying phasic synaptic activity, that could explain the bursting behavior. 4. Type-1 neurons showed delayed excitation after hyperpolarizing square current pulses or when the neurons were depolarized from a hyperpolarized level. This membrane behavior resembles the response seen in other CNS neurons expressing an IA. The response to 1-s long depolarizing pulses with a large current strength showed signs of activation of an active depolarizing membrane response leading to a transient reduction in the spike amplitude. The relationship between the membrane potential and the amplitude of square current pulses (Vm-I) showed a small upward rectification below -70 mV, and spike adaptation throughout a 1-s pulse had a largely linear time course. 5. Type-1 neurons depolarized and started to fire spikes 398 +/- 102 ms (n = 20) before the upstroke of the integrated XII nerve discharge. The inspiratory potential was followed by fast hyperpolarization, a short fast-repolarizing phase (1,040 +/- 102 ms, n = 5) and a longer slow-repolarizing phase (lasting until the next inspiratory discharge). 6. Type-2 neurons were spiking in the interval between the inspiratory potentials with no evidence of bursting behavior and had an input resistance of 296 +/- 212 M omega (n = 26). The response to hyperpolarizing pulses revealed an initial sag and postinhibitory rebound depolarization. This membrane behavior resembles the response seen in other CNS neurons expressing an Ih. The Vm-I relationship was linear at depolarized potentials and showed a marked upward rectification below -60 mV. Spike trains elicited by 1-s long pulses showed a pronounced early and late adaptation. 7. Type-2 neurons depolarized and started to fire spikes 171 +/- 87 ms (n = 23) before the upstroke of the integrated XII nerve discharge. The inspiratory potential had a variable amplitude from cell to cell and was followed by a short hyperpolarization in the cells displaying a large amplitude inspiratory potential.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of stimulus duration on responses of neurons in the chinchilla inferior colliculus

The effects of the stimulus duration (10 to 300 ms) on the responses of chinchilla inferior colliculus neurons to pure tones were studied in 41 units. The responses of the majority of the neurons (90%) were classified as sustained, onset, pause with onset peak and pause without onset peak response patterns. Three neurons were found to have response to the stimulus offset (offset response pattern). One neuron responded to the sound with the decrease of the spontaneous discharge rate (inhibitory response pattern). The responses restricted within the stimulus duration could be simply predicted from the peristimulus time histogram (PSTH) to the longer duration. The leading part of the PSTH to the longer stimulus duration resembled that to the shorter stimulus duration. The function of the spike number versus duration was correlated with the PSTH patterns. The response following the stimulus offset (including inhibitory response) could vary with the stimulus duration nonmonotonically and show a band-pass or band-reject property. Overall, four (about 10%) of the neurons could be regarded as duration-tuned units. The duration selectivity could be understood by the interaction between the ongoing and the offset process of the neurons.     

Long-latency neurons in auditory cortex involved in temporal integration: theoretical analysis of experimental data

A previous experimental study (He et al., 1997) found 132 duration-selective neurons with long latencies of greater than 30 ms in the dorsal zone of cat auditory cortex. The mechanism by which such long-latency neurons integrate information during their latent period is investigated by analysis of the temporal relationship between the stimulus and neuronal response. In the present study, we developed a one-layer perceptron to examine the above temporal relationship of the experimental results. The acoustic stimulus was represented as a contiguous series of sequential short time epochs. The perceptron was trained by using the spike data as the desired outputs and the acoustic stimuli (in digital format) as the inputs. The adaptive weights between the outputs and the inputs after training indicated the temporal relationship between neuronal responses and the stimuli. The contribution of each time epoch of the stimulus could be either positive or negative: the positive contribution corresponds to excitatory input and the negative contribution to inhibitory input. Long-duration-selective neurons were found to receive mainly excitatory input along the entire effective stimulus duration. However, duration-tuned neurons received excitatory input for only the time period from the stimulus onset to their best durations, and inhibitory thereafter. The temporal integration pattern of short-duration-selective neurons was similar to duration-tuned neurons. However, short-duration-selective neurons received excitatory input only at the beginning of the stimulus. Each of the duration-threshold neurons integrated auditory information only for a restricted time period of the stimulus, suggesting that they have a time window over the stimulus time domain. Non-duration-threshold neurons have time windows extending from the stimulus onset onward. The assembly of duration-threshold neurons and non-duration-threshold neurons may collectively represent the time axis of the stimulus.     

On the relationship between synaptic input and spike output jitter in individual neurons

What is the relationship between the temporal jitter in the arrival times of individual synaptic inputs to a neuron and the resultant jitter in its output spike? We report that the rise time of firing rates of cells in striate and extrastriate visual cortex in the macaque monkey remain equally sharp at different stages of processing. Furthermore, as observed by others, multiunit recordings from single units in the primate frontal lobe reveal a strong peak in their cross-correlation in the 10-150 msec range with very small temporal jitter (on the order of 1 msec). We explain these results using numerical models to study the relationship between the temporal jitter in excitatory and inhibitory synaptic input and the variability in the spike output timing in integrate-and-fire units and in a biophysically and anatomically detailed model of a cortical pyramidal cell. We conclude that under physiological circumstances, the standard deviation in the output jitter is linearly related to the standard deviation in the input jitter, with a constant of less than one. Thus, the timing jitter in successive layers of such neurons will converge to a small value dictated by the jitter in axonal propagation times.     

Efficient discrimination of temporal patterns by motion-sensitive neurons in primate visual cortex

Although motion-sensitive neurons in macaque middle temporal (MT) area are conventionally characterized using stimuli whose velocity remains constant for 1-3 s, many ecologically relevant stimuli change on a shorter time scale (30-300 ms). We compared neuronal responses to conventional (constant-velocity) and time-varying stimuli in alert primates. The responses to both stimulus ensembles were well described as rate-modulated Poisson processes but with very high precision (approximately 3 ms) modulation functions underlying the time-varying responses. Information-theoretic analysis revealed that the responses encoded only approximately 1 bit/s about constant-velocity stimuli but up to 29 bits/s about the time-varying stimuli. Analysis of local field potentials revealed that part of the residual response variability arose from "noise" sources extrinsic to the neuron. Our results demonstrate that extrastriate neurons in alert primates can encode the fine temporal structure of visual stimuli.     

Antidromic responses of single units from the spiral ganglion

1. Antidromic responses of single units in the guinea pig spiral ganglion were recorded in response to shocks to the auditory nerve root. The orthodromic responses of these units were also recorded in response to sound. The aim of this study was 1) to classify units according to their response patterns to shocks and to sound and 2) to propose anatomic types that might correlate with these responses. The four classes of units were as follows: type I, olivocochlear (OC), long-latency: locked, and long-latency: jittering. 2. Type I units responded antidromically to shocks with little jitter and short latency. Their responses to sound were also of short latency and had irregular interspike intervals. Some of these units had complex spike waveforms. These units likely correspond to type I primary afferent neurons, the majority population of spiral ganglion cells. 3. One-third of the OC units responded to shocks, with little jitter and intermediate latency (2 ms). OC unit responses to sound were of long latency and had regular interspike intervals. These units likely correspond to efferent neurons that originate in the superior olivary complex of the brain and end on outer hair cells in the cochlea. 4. Long-latency: locked units responded to shocks with little jitter and long latency (4-11 ms). Many of these units had complex spike waveforms and most did not respond to high-level noise bursts. Long-latency: locked units may correspond to type II spiral ganglion neurons. 5. Long-latency: jittering units responded to shocks with a jitter of several milliseconds and long latency. Some of these units responded to sound in a pattern reminiscent of OC units. These units may constitute a subgroup of OC units that respond to shocks via activation of the reflex pathway from the cochlea to the superior olive and back out to the cochlea. 6. Further data were collected on the type I response to shocks. Antidromic spikes lacked the inflections seen on the waveforms that are typically seen on orthodromic spikes. Type I shock responses depended on shock level and duration and were reduced when a click preceded the shock by approximately 2 ms. Several type I characteristics depended on the rate of spontaneous discharge: for units of low and medium spontaneous rates (when compared with units of high rates), the shock thresholds were lower, shock latencies were longer, and the probability of firing repetitive spikes to a single shock was higher.(ABSTRACT TRUNCATED AT 400 WORDS)     

Isolation and characterization of a persistent potassium current in neostriatal neurons

1. Depolarization-activated, calcium-independent potassium (K+) currents were studied with the use of whole cell voltage-clamp recording from neostriatal neurons acutely isolated from adult (> or = 4 wk old) rats. The whole cell K+ current was composed of transient and persistent components. The aims of the experiments were to isolate the persistent component and then to characterize its voltage dependence and kinetics. 2. Application of 10 mM 4-aminopyridine (4-AP) completely blocked the transient currents while reducing the persistent current by approximately 40% [50% inhibitory concentration (IC50), of blockable current = 125 microM]. The persistent K+ current also was reduced by tetraethylammonium (TEA). Two components to the TEA block were present, having IC50s of 125 microM (23% of the blockable current) and 5.9 mM (77% of the blockable current). Collectively, these results suggested that the persistent components of the total K+ current was pharmacologically heterogeneous. The properties of the 4-AP-resistant, persistent K+ current (IKrp) were subsequently studied. 3. The kinetics of activation and deactivation of IKrp were voltage dependent. Examination of the entire activation/deactivation time constant profile showed that it was bell shaped, with time constants being moderately rapid (tau approximately 50 ms) at membrane potentials corresponding to the resting potential of neostriatal cells (approximately -80 mV), becoming considerably longer (tau approximately 100 ms) at potentials near the cells' spike thresholds (approximately -45 mV), and decreasing to a minimum (tau approximately 5 ms) at potentials associated with the peak of the cells' action potentials (approximately +20 mV). The inactivation kinetics of IKrp also were voltage dependent. The time constants of inactivation varied between 1 and 8 s at potentials between -10 and +35 mV. 4. Unlike persistent K+ currents in many other cell types, IKrp activated at relatively hyperpolarized membrane potentials (approximately -70 mV). The Boltzmann function describing activation had a half-activation voltage of -13 mV and a slope factor of 12 mV. In addition, the Boltzmann function describing the voltage dependence of inactivation of IKrp had a relatively depolarized half-inactivation voltage of -55 and a large slope factor of 19 mV, indicating that this current was available over a broad range of membrane potentials (between -100 and -10 mV). 5. Neostriatal neurons recorded in vivo exhibit subthreshold shifts in membrane potential of variable duration (tens of ms to s) from a hyperpolarized resting state to a depolarized state that is limited in amplitude just below spike threshold. The voltage dependence of activation and inactivation of IKrp indicates that it will be available on depolarization from the hyperpolarized state. However, the slow activation rate of this current suggests that it will contribute little either to limiting the amplitude of the initial depolarization associated with entry into the depolarized state or to depolarizing episodes of short duration (e.g., < 50 ms). However, IKrp should limit the amplitude of membrane depolarizations associated with prolonged excursions into the depolarized state.     

The discrimination of temporal fine structure in call-like harmonic sounds by birds.

Thresholds for discriminating changes in the temporal fine structure of call-like, harmonic sounds were measured in zebra finches (Taeniopygia guttata) and budgerigars (Melopsittacus undulatus). Birds could detect changes in periods as short as 1.225 ms at near 100% accuracy even when spectral and envelope cues were identical, as in time-reversed stimuli. Humans performed poorly on such stimuli, paralleling results from previous studies. Bird thresholds were in the range of those reported in neurophysiological studies of the songbird high vocal center (HVC) to temporally modified conspecific songs. Taken together, these results show that birds can hear differences in temporal fine structure in their natural vocalizations that go beyond human capabilities, but whether these abilities have communicative relevance remains to be seen. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Slow covariations in neuronal resting potentials can lead to artefactually fast cross-correlations in their spike trains

Slow covariations in neuronal resting potentials can lead to artefactually fast cross-correlations in their spike trains. J. Neurophysiol. 80: 3345-3351, 1998. A model of two lateral geniculate nucleus (LGN) cells, which interact only through slow (tens of seconds) covariations in their resting membrane potentials, is used here to investigate the effect of such covariations on cross-correlograms taken during stimulus-driven conditions. Despite the slow timescale of the interactions, the model generates cross-correlograms with peak widths in the range of 25-200 ms. These bear a striking resemblance to those reported in studies of LGN cells by Sillito et al., which were taken at the time as evidence of a fast spike timing synchronization interaction; the model highlights the possibility that those correlogram peaks may have been caused by a mechanism other than spike synchronization. Slow resting potential covariations are suggested instead as the dominant generating mechanism. How can a slow interaction generate covariogram peaks with a width 100-1,000 times thinner than its timescale? Broad peaks caused by slow interactions are modulated by the cells' poststimulus time histograms (PSTHs). When the PSTHs have thin peaks (e.g., tens of milliseconds), the cross-correlogram peaks generated by slow interactions will also be thin; such peaks are easily misinterpretable as being caused by fast interactions. Although this point is explored here in the context of LGN recordings, it is a general point and applies elsewhere. When cross-correlogram peak widths are of the same order of magnitude as PSTH peak widths, experiments designed to reveal short-timescale interactions must be interpreted with the issue of possible contributions from slower interactions in mind.     

Temporal acuity in auditory function in the rat: Reflex inhibition by brief gaps in noise.

Previous results show that the acoustic startle reflex in the rat is inhibited if a relatively weak stimulus precedes the startle-eliciting tone burst. The present 5 experiments explored the effect of brief silent periods (gaps) in white noise on the startle reflex in order to describe the limits of temporal resolution in the auditory system of 12 Long-Evans hooded rats. Brief silent periods did depress reflex behavior, and 2 responsible processes were identified. One was most evident at a 190-msec lead time between gap and startle tone. It yielded a linear decrement in reflex expression over a dynamic range of 0–7 msec and an estimate for the threshold of temporal acuity of 3.5 msec. The 2nd was evident primarily at a 40-msec interstimulus interval and had a linear effect over a dynamic range of at least 40 msec. Brief gaps had a greater inhibitory effect at the 190-msec interval between gap and startle stimulus; prolonged gaps had their greater effect at the 40-msec interval. The 1st process was identified as reflex inhibition, which is sensitive to the sensory properties of the lead stimulus. The 2nd process was identified as sensory adaptation, produced by noise exposure but unmasked by silence. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The third five-year survey of fellows (by examination) of the Faculty of Intensive Care, Australian and New Zealand College of Anaesthetists

The activity of the pedunculopontine tegmental nucleus (PPTg) neurons was recorded in three unrestrained cats operantly conditioned to perform a lever-release movement. The movement had to be initiated either rapidly after a (click) stimulus in a simple reaction-time paradigm or had to be delayed after the same stimulus in trials identified by a tone cue. Successful trials were rewarded by a food pellet. A total of 107 neurons were recorded with microelectrodes. Brief spike neurons (mean duration: 0.7 ms) and broad spike neurons (mean duration: 2 ms) presumed to be cholinergic were detected. Of the 73 neurons localized in the PPTg area, 53 had brief spikes and 20 broad spikes. Changes in activity most commonly occurred very early after the stimulus or during the reinforcement process. Most neurons with brief spikes exhibited very early excitation after the stimulus and reinforcement-related activity. These neurons had a mean activity of 23.7 impulses/s in the period preceding the stimulus. The onset of activation after the stimulus had a latency of 8.6+/-6.9 ms (mean+/-SD), with a range of 4-35 ms. In trials where the movement had to be delayed after the stimulus, the early activation disappeared or was considerably reduced, showing that it was context-dependent. A small proportion of neurons with brief spikes initially decreased activity after the stimulus, but with a latency >9 ms. All the neurons with broad spikes, except one, had reinforcement-related activity. Half of them showed exclusively reinforcement-related activity, the other half also early activation after the stimulus. These neurons were about half as active in the period preceding the stimulus occurrence than the neurons with brief spikes. The early context-dependent activation is discussed in relation to the excitatory projection of PPTg neurons on the subthalamic nucleus. The reinforcement-related activity, preferentially evidenced in broad spike neurons presumed to be cholinergic, is speculated to be associated with cholinergic projection of PPTg neurons to the dopaminergic neurons of the substantia nigra. Finally, the role of PPTg in the ongoing control of motor performance and reinforcement processes is discussed in relation to the basal ganglia circuitry.