Single Unit publications

Sensory systems are known to adapt their coding strategies to the statistics of their environment, but little is still known about the perceptual implications of such adjustments. We investigated how auditory spatial processing adapts to stimulus statistics by presenting human listeners and anesthetized ferrets with noise sequences in which interaural level differences (ILD) rapidly fluctuated according to a Gaussian distribution. The mean of the distribution biased the perceived laterality of a subsequent stimulus, whereas the distribution's variance changed the listeners' spatial sensitivity. The responses of neurons in the inferior colliculus changed in line with these perceptual phenomena. Their ILD preference adjusted to match the stimulus distribution mean, resulting in large shifts in rate-ILD functions, while their gain adapted to the stimulus variance, producing pronounced changes in neural sensitivity. Our findings suggest that processing of auditory space is geared toward emphasizing relative spatial differences rather than the accurate representation of absolute position.

Acipenser fulvescens, the lake sturgeon, belongs to one of the few extant non-teleost ray-finned (bony) fishes. The sturgeons (family Acipenseridae) have a phylogenetic history that dates back about 250 million years. The study reported here is the first investigation of peripheral coding strategies for spectral analysis in the auditory system in a non-teleost bony fish. We used a shaker system to simulate the particle motion component of sound during electrophysiological recordings of isolated single units from the eighth nerve innervating the saccule and lagena. Background activity and response characteristics of saccular and lagenar afferents (such as thresholds, response–level functions and temporal firing) resembled the ones found in teleosts. The distribution of best frequencies also resembled data in teleosts (except for Carassius auratus, goldfish) tested with the same stimulation method. The saccule and lagena in A. fulvescens contain otoconia, in contrast to the solid otoliths found in teleosts, however, this difference in otolith structure did not appear to affect threshold, frequency tuning, intensity- or temporal responses of auditory afferents. In general, the physiological characteristics common to A. fulvescens, teleosts and land vertebrates reflect important functions of the auditory system that may have been conserved throughout the evolution of vertebrates.

Neurons in the auditory cortex of anesthetized animals are generally considered to generate phasic responses to simple stimuli such as tones or noise bursts. In this paper, we show that under ketamine/medetomidine anesthesia, neurons in ferret auditory cortex usually exhibit complex sustained responses. We presented 100-ms broad-band noise bursts at a range of interaural level differences (ILDs) and average binaural levels (ABLs), and used extracellular electrodes to monitor evoked activity over 700 ms poststimulus onset. We estimated the degree of randomness (noise) in the response functions of individual neurons over poststimulus time; we found that neural activity was significantly modulated by sound for up to ∼500 ms following stimulus offset. Pooling data from all neurons, we found that spiking activity carries significant information about stimulus identity over this same time period. However, information about ILD decayed much more quickly over time compared with information about ABL. In addition, ILD and ABL are coded independently by the neural population even though this is not the case at individual neurons. Though most neurons responded more strongly to ILDs corresponding to the opposite side of space, as a population, they were equally informative about both contra- and ipsilateral stimuli.

Background: Barn owls integrate spatial information across frequency channels to localize sounds in space. Methodology/principal findings: We presented barn owls with synchronous sounds that contained different bands of frequencies (3-5 kHz and 7-9 kHz) from different locations in space. When the owls were confronted with the conflicting localization cues from two synchronous sounds of equal level, their orienting responses were dominated by one of the sounds: they oriented toward the location of the low frequency sound when the sources were separated in azimuth; in contrast, they oriented toward the location of the high frequency sound when the sources were separated in elevation. We identified neural correlates of this behavioral effect in the optic tectum (OT, superior colliculus in mammals), which contains a map of auditory space and is involved in generating orienting movements to sounds. We found that low frequency cues dominate the representation of sound azimuth in the OT space map, whereas high frequency cues dominate the representation of sound elevation. Conclusions/significance: Significance: We argue that the dominance hierarchy of localization cues reflects several factors: 1) the relative amplitude of the sound providing the cue, 2) the resolution with which the auditory system measures the value of a cue, and 3) the spatial ambiguity in interpreting the cue. These same factors may contribute to the relative weighting of sound localization cues in other species, including humans.

Neurons in the primary visual cortex typically reach their highest firing rate after an abrupt image transition. Since the mutual information between the firing rate and the currently presented image is largest during this early firing period it is tempting to conclude this early firing encodes the current image. This view is, however, made more complicated by the fact that the response to the current image is dependent on the preceding image. Therefore we hypothesize that neurons encode a combination of current and previous images, and that the strength of the current image relative to the previous image changes over time. The temporal encoding is interesting, first, because neurons are, at different time points, sensitive to different features such as luminance, edges and textures; second, because the temporal evolution provides temporal constraints for deciphering the instantaneous population activity. To study the temporal evolution of the encoding we presented a sequence of 250 ms stimulus patterns during multiunit recordings in areas 17 and 18 of the anaesthetized ferret. Using a novel method we decoded the pattern given the instantaneous population-firing rate. Following a stimulus transition from stimulus A to B the decoded stimulus during the first 90ms was more correlated with the difference between A and B (B-A) than with B alone. After 90ms the decoded stimulus was more correlated with stimulus B than with B-A. Finally we related our results to information measures of previous (B) and current stimulus (A). Despite that the initial transient conveys the majority of the stimulus-related information; we show that it actually encodes a difference image which can be independent of the stimulus. Only later on, spikes gradually encode the stimulus more exclusively.

We report the results of extracellular single‐unit recording experiments where we quantitatively analyzed the receptive‐field (RF) properties of neurons in V1 and an adjacent extrastriate visual area (V2L) of anesthetized mice with emphasis on the RF center‐surround organization. We compared the results with the RF center‐surround organization of V1 and V2 neurons in macaque monkeys. If species differences in spatial scale are taken into consideration, mouse V1 and V2L neurons had remarkably fine stimulus selectivity, and the majority of response properties in V2L were not different from those in V1. The RF center‐surround organization of mouse V1 neurons was qualitatively similar to that for macaque monkeys (i.e., the RF center is surrounded by extended suppressive regions). However, unlike in monkey V2, a significant proportion of cortical neurons, largely complex cells in V2L, did not exhibit quantifiable RF surround suppression. Simple cells had smaller RF centers than complex cells, and the prevalence and strength of surround suppression were greater in simple cells than in complex cells. These findings, particularly on the RF center‐surround organization of visual cortical neurons, give new insights into the principles governing cortical circuits in the mouse visual cortex and should provide further impetus for the use of mice in studies on the genetic and molecular basis of RF development and synaptic plasticity. J. Comp. Neurol. 518:2051–2070, 2010. © 2010 Wiley‐Liss, Inc.

Psychophysical forward masking is an increase in threshold of detection of a sound (probe) when it is preceded by another sound (masker). This is reminiscent of the reduction in neuronal responses to a sound following prior stimulation. Studies in the auditory nerve and cochlear nucleus using signal detection theory techniques to derive neuronal thresholds showed that in centrally projecting neurons, increases in masked thresholds were significantly smaller than the changes measured psychophysically. Larger threshold shifts have been reported in the inferior colliculus of awake marmoset. The present study investigated the magnitude of forward masking in primary auditory cortical neurons of anaesthetised guinea-pigs. Responses of cortical neurons to unmasked and forward masked tones were measured and probe detection thresholds estimated using signal detection theory methods. Threshold shifts were larger than in the auditory nerve, cochlear nucleus and inferior colliculus. The larger threshold shifts suggest that central, and probably cortical, processes contribute to forward masking. However, although methodological differences make comparisons difficult, the threshold shifts in cortical neurons were, in contrast to subcortical nuclei, actually larger than those observed psychophysically. Masking was largely attributable to a reduction in the responses to the probe, rather than either a persistence of the masker responses or an increase in the variability of probe responses.

We measured the responses of neurons in auditory cortex of male and female ferrets to artificial vowels of varying fundamental frequency ( f 0 ), or periodicity, and compared these with the performance of animals trained to discriminate the periodicity of these sounds. Sensitivity to f 0 was found in all five auditory cortical fields examined, with most of those neurons exhibiting either low-pass or high-pass response functions. Only rarely was the stimulus dependence of individual neuron discharges sufficient to account for the discrimination performance of the ferrets. In contrast, when analyzed with a simple classifier, responses of small ensembles, comprising 3-61 simultaneously recorded neurons, often discriminated periodicity changes as well as the animals did. We examined four potential strategies for decoding ensemble responses: spike counts, relative first-spike latencies, a binary “spike or no-spike” code, and a spike-order code. All four codes represented stimulus periodicity effectively, and, surprisingly, the spike count and relative latency codes enabled an equally rapid readout, within 75 ms of stimulus onset. Thus, relative latency codes do not necessarily facilitate faster discrimination judgments. A joint spike count plus relative latency code was more informative than either code alone, indicating that the information captured by each measure was not wholly redundant. The responses of neural ensembles, but not of single neurons, reliably encoded f 0 changes even when stimulus intensity was varied randomly over a 20 dB range. Because trained animals can discriminate stimulus periodicity across different sound levels, this implies that ensemble codes are better suited to account for behavioral performance.

Closed-loop neural interface technology that combines neural ensemble decoding with simultaneous electrical microstimulation feedback is hypothesized to improve deep brain stimulation techniques, neuromotor prosthetic applications, and epilepsy treatment. Here we describe our iterative results in a rat model of a sensory and motor neurophysiological feedback control system. Three rats were chronically implanted with microelectrode arrays in both the motor and visual cortices. The rats were subsequently trained over a period of weeks to modulate their motor cortex ensemble unit activity upon delivery of intra-cortical microstimulation (ICMS) of the visual cortex in order to receive a food reward. Rats were given continuous feedback via visual cortex ICMS during the response periods that was representative of the motor cortex ensemble dynamics. Analysis revealed that the feedback provided the animals with indicators of the behavioral trials. At the hardware level, this preparation provides a tractable test model for improving the technology of closed-loop neural devices.

During anesthesia, slow-wave sleep and quiet wakefulness, neuronal membrane potentials collectively switch between de- and hyperpolarized levels, the cortical UP and DOWN states. Previous studies have shown that these cortical UP/DOWN states affect the excitability of individual neurons in response to sensory stimuli, indicating that a significant amount of the trial-to-trial variability in neuronal responses can be attributed to ongoing fluctuations in network activity. However, as intracellular recordings are frequently not available, it is important to be able to estimate their occurrence purely from extracellular data. Here, we combine in vivo whole cell recordings from single neurons with multi-site extracellular microelectrode recordings, to quantify the performance of various approaches to predicting UP/DOWN states from the deep-layer local field potential (LFP). We find that UP/DOWN states in deep cortical layers of rat primary auditory cortex (A1) are predictable from the phase of LFP at low frequencies (< 4 Hz), and that the likelihood of a given state varies sinusoidally with the phase of LFP at these frequencies. We introduce a novel method of detecting cortical state by combining information concerning the phase of the LFP and ongoing multi-unit activity.

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical–hippocampal communication. Here, in unanesthetized 5- to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.

Brain-machine interfaces (BMIs) use signals recorded directly from the brain to control an external device, such as a computer cursor or a prosthetic limb. These control signals have been recorded from different levels of the brain, from field potentials at the scalp or cortical surface to single neuron action potentials. At present, the more invasive recordings have better signal quality, but also lower stability over time. Recently, subdural field potentials have been proposed as a stable, good quality source of control signals, with the potential for higher spatial and temporal bandwidth than EEG. Here we used finite element modeling in rats and humans and spatial spectral analysis in rats to compare the spatial resolution of signals recorded epidurally (outside the dura), with those recorded from subdural and scalp locations. Resolution of epidural and subdural signals was very similar in rats and somewhat less so in human models. Both were substantially better than signals recorded at the scalp. Resolution of epidural and subdural signals in humans was much more similar when the cerebrospinal fluid layer thickness was reduced. This suggests that the less invasive epidural recordings may yield signals of similar quality to subdural recordings, and hence may be more attractive as a source of control signals for BMIs.

The rapidly increasing use of the local field potential (LFP) has motivated research to better understand its relation to the gold standard of neural activity, single unit (SU) spiking. We addressed this in an in vivo, awake, restrained mouse auditory cortical electrophysiology preparation by asking whether the LFP could actually be used to predict stimulus-evoked SU spiking. Implementing a Bayesian algorithm to predict the likelihood of spiking on a trial by trial basis from different representations of the despiked LFP signal, we were able to predict, with high quality and fine temporal resolution (2 ms), the time course of a SU's excitatory or inhibitory firing rate response to natural species-specific vocalizations. Our best predictions were achieved by representing the LFP by its wide-band Hilbert phase signal, and approximating the statistical structure of this signal at different time points as independent. Our results show that each SU's action potential has a unique relationship with the LFP that can be reliably used to predict the occurrence of spikes. This "signature" interaction can reflect both pre- and post-spike neural activity that is intrinsic to the local circuit rather than just dictated by the stimulus. Finally, the time course of this "signature" may be most faithful when the full bandwidth of the LFP, rather than specific narrow-band components, is used for representation.

The lateral superior olive (LSO) is one of the earliest sites in the auditory pathway involved in processing acoustical cues to sound location. LSO neurons encode the interaural level difference (ILD) cue to azimuthal location. Here we investigated the effect of variations in the overall stimulus levels of sounds at the two ears on the sensitivity of LSO neurons to small differences in ILDs of pure tones. The neuronal firing rate versus ILD functions were found to depend greatly on the overall stimulus level, typically shifting along the ILD axis toward the excitatory ear and attaining greater maximal firing rates as stimulus level increased. Seventy-five percent of neurons showed significant shifts with changes in overall sound level. The range of ILDs corresponding to best neural acuity for ILDs shifted accordingly. In a simulation using the empirical data, when the overall stimulus level was randomly changed from one trial to the next, the neural discrimination thresholds for ILD, or ILD acuities, were worsened by 50–60% across the population of neurons relative to fixed stimulus levels whether ILD acuity was measured at the azimuthal midline or the ILD pedestal producing the best acuity. The impairment in ILD discrimination was attributed to the increased neural response variance imparted by varying the stimulus level. These results contrast to those observed in psychophysical studies where ILD discrimination thresholds under similar experimental conditions are invariant to overall changes in stimulus level. A simple computational model that incorporated the antagonistic inputs of bilateral LSO nuclei as well as the dorsal nuclei of the lateral lemniscus to the inferior colliculus produced a more robust encoding of ILD even in the setting of roving stimulus level. Testable predictions of this model and comparison to other computational models addressing stimulus invariance were considered.

Spontaneous activity is a well-known neural phenomenon that occurs throughout the brain and is essential for normal development of auditory circuits and for processing of sounds. Spontaneous activity could interfere with sound processing by reducing the signal-to-noise ratio. Multiple studies have reported that spontaneous activity in auditory neurons can be suppressed by sound stimuli. The goal of this study was to determine the stimulus conditions that cause this suppression and to identify possible underlying mechanisms. Experiments were conducted in the inferior colliculus (IC) of awake little brown bats using extracellular and intracellular recording techniques. The majority of IC neurons (82%) fired spontaneously, with a median spontaneous firing rate of 6 spikes/s. After offset of a 4 ms sound, more than half of these neurons exhibited suppression of spontaneous firing that lasted hundreds of milliseconds. The duration of suppression increased with sound level. Intracellular recordings showed that a short (<50 ms) membrane hyperpolarization was often present during the beginning of suppression, but it was never observed during the remainder of the suppression. Beyond the initial 50 ms period, the absence of significant changes in input resistance during suppression suggests that suppression is presynaptic in origin. Namely, it may occur on presynaptic terminals and/or elsewhere on presynaptic neurons. Suppression of spontaneous firing may serve as a mechanism for enhancing signal-to-noise ratios during signal processing.

Functional and anatomical studies suggest that acoustic signals are processed hierarchically in auditory cortex. Although most regions of acoustically responsive cortex are not tonotopically organized, all previous electrophysiological investigations of interfield interactions have only examined tonotopically represented areas. The purpose of the present study was to investigate the functional interactions between tonotopically and nontonotopically organized fields in auditory cortex. We accomplished this goal by examining the bidirectional contributions between the cochleotopically organized primary auditory cortex (A1) and the noncochleotopically organized second auditory field (A2). Multiunit acute recording procedures in combination with reversible cooling deactivation techniques were used in eight mature cats. The synaptic activity of A1 or A2 was suppressed while the neuronal response to tonal stimuli of the noninactivated area (A1 or A2) was measured. Response strength, neuronal threshold, receptive field bandwidths, and latency measures were collected at each recorded site before, during, and after cooling deactivation epochs. Our analysis revealed comparable changes in A1 and A2 neuronal response properties. Specifically, significant decreases in neuronal response strength, increases in neuronal threshold, and shortening of response latency were found in both fields during periods of cooling deactivation. The weak anatomical connections between the two fields investigated make these findings unexpected. Furthermore, the observed neuronal changes suggest a model of corticocortical interaction among auditory fields in which neither differences in the magnitude of anatomical projections nor cortical representation of sensory stimuli are reliable determinants of modulatory functions.

Previous studies have shown that hand translation is well represented by neuronal activity in the proximal arm area of primary motor cortex (M1). However, little is known about cortical representation of hand rotation in M1. In this study, single-unit activity was recorded from monkeys while they performed a “center-out with rotation” task. When reaching for a target, subjects had to match four separate kinematic parameters: three-dimensional location and one-dimensional orientation of the target. Among the 512 neurons modulated by hand movement, 446 were tuned to hand translation, 326 were tuned to hand rotation, and 260 neurons were tuned to both hand translation and hand rotation. Approximately half of the neurons that encoded both translation and rotation did so in a nonlinear manner. This nonlinear interaction can be modeled as a gain-field type of encoding whereby hand rotational velocity modulated the hand translational cosine tuning curves in a multiplicative manner. Furthermore, this study demonstrated that both hand translation and hand rotation can be decoded simultaneously from a population of motor cortical neurons.

Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model of activity-dependent neural plasticity that is restricted to an early critical period regulated by maturation of inhibition. Unique developmental plasticity mechanisms may improve outcomes following early brain injury. Our objective was to determine the effects of neonatal cerebral hypoxia–ischemia (HI) on ODP. The rationale extends from observations that neonatal HI results in death of subplate neurons, a transient population known to influence development of inhibition. In rodents subjected to neonatal HI and controls, maps of visual response were derived from optical imaging during the critical period for ODP and changes in the balance of eye-specific response following MD were measured. In controls, MD results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to −0.10 ( p < 0.001). Neonatal HI with moderate cortical injury impairs this shift, ODI = 0.14 ( p < 0.01). Plasticity was intact in animals with mild injury and in those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus 35.0 cells/high-power field ( p = 0.01), with no change in other markers of inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype, spontaneous activity of single units and development of orientation selective responses were intact following neonatal HI, while overall visual responses were reduced. Our data suggest that specific plasticity mechanisms are impaired following early brain injury and that the impairment is associated with altered inhibitory neuronal development and cortical activation.

Phase-locked spikes in various types of neurons encode temporal information. To quantify the degree of phase-locking, the metric called vector strength (VS) has been most widely used. Since VS is derived from spike timing information, error in measurement of spike occurrence should result in errors in VS calculation. In electrophysiological experiments, the timing of an action potential is detected with finite temporal precision, which is determined by the sampling frequency. In order to evaluate the effects of the sampling frequency on the measurement of VS, we derive theoretical upper and lower bounds of VS from spikes collected with finite sampling rates. We next estimate errors in VS assuming random sampling effects, and show that our theoretical calculation agrees with data from electrophysiological recordings in vivo. Our results provide a practical guide for choosing the appropriate sampling frequency in measuring VS.

Descending cortical inputs to the superior colliculus (SC) contribute to the unisensory response properties of the neurons found there and are critical for multisensory integration. However, little is known about the relative contribution of different auditory cortical areas to this projection or the distribution of their terminals in the SC. We characterized this projection in the ferret by injecting tracers in the SC and auditory cortex. Large pyramidal neurons were labeled in layer V of different parts of the ectosylvian gyrus after tracer injections in the SC. Those cells were most numerous in the anterior ectosylvian gyrus (AEG), and particularly in the anterior ventral field, which receives both auditory and visual inputs. Labeling was also found in the posterior ectosylvian gyrus (PEG), predominantly in the tonotopically organized posterior suprasylvian field. Profuse anterograde labeling was present in the SC following tracer injections at the site of acoustically responsive neurons in the AEG or PEG, with terminal fields being both more prominent and clustered for inputs originating from the AEG. Terminals from both cortical areas were located throughout the intermediate and deep layers, but were most concentrated in the posterior half of the SC, where peripheral stimulus locations are represented. No inputs were identified from primary auditory cortical areas, although some labeling was found in the surrounding sulci. Our findings suggest that higher level auditory cortical areas, including those involved in multisensory processing, may modulate SC function via their projections into its deeper layers.